Clinical Trials

Clinical Trials @ CRC

If interested in any of the following studies, call the research Hotline at (808) 564-6141 or email Study@HawaiiNeuroscience.com

Sub-study to evaluate the effects of Ofatumumab subcutaneous treatment on the immune responses following Vaccination in patients with relapsing forms of Multiple Sclerosis

Inclusion
1. Subject must be actively enrolled in the COMB157G2399 Open-label extension study
2. Subject must have received at least 12 weeks of continuous open-label ofatumumab treatment  immediately prior to sub-study vaccination with TT
3. For Vaccination Series 2, subjects must have received at least 12 weeks of continuous open-label ofatumumab treatment immediately prior to the first influenza vaccination
Note: Continuous treatment is defined as not having any ofatumumab treatment interruptions during the 12 weeks immediately prior to sub-study vaccination with TT or the first influenza  vaccination
4. Subject must have received at least one previous immunization against TT, or tetanus and diphtheria (DT/Td), or tetanus, diphtheria, and acellular pertussis (DTaP/Tdap), or tetanus, diphtheria, acellular pertussis, inactivated polio vaccine (Tdap-IPV), or other TT containing vaccines with last booster vaccination administered a maximum of 10 years prior to being enrolled in the sub-study

ND0612-317: A Clinical Trial Investigating the Efficacy, Safety and Tolerability of Continuous Subcutaneous ND0612 Infusion in Comparison to Oral IR-LD/CD in Subjects With Parkinson's Disease Experiencing Motor Fluctuations (BouNDless)

This is a phase III multi-center, randomized, active-controlled, double-blind, double-dummy, parallel group clinical trial, investigating the efficacy, safety, and tolerability of continuous subcutaneous ND0612 infusion in comparison to oral IR-LD/CD in subjects with Parkinson’s disease experiencing motor fluctuations.

This study is comprised of 6 periods:

  1. a Screening Period;

  2. an open-label oral IR-LD/CD Adjustment Period.

  3. an open-label ND0612 Conversion Period.

  4. a randomized, double-blind, double-dummy, active-controlled Maintenance Period.

  5. an optional open-label Treatment Extension; and

  6. a Safety Follow-up Period.

Inclusion Criteria:

  1. Male and female patients, aged ≥30 years.

  2. PD diagnosis consistent with the UK Brain Bank Criteria.

  3. Modified Hoehn & Yahr score ≤3 during ON.

  4. Average of ≥2.5 hours of OFF time (≥2 hours OFF every day) during waking hours as confirmed by patient diary over 3 days.

  5. Taking ≥4 levodopa doses/day (≥3 doses/day of Rytary) at a total daily dose of ≥400mg.

Exclusion Criteria:

  1. Atypical or secondary parkinsonism.

  2. Severe disabling dyskinesias.

  3. Previous neurosurgery for PD.

  4. Use of duodenal levodopa infusion (LCIG)* or apomorphine infusion.

  5. Use of the following medications: subcutaneous apomorphine injections, sublingual apomorphine, or inhaled levodopa within 4 weeks.

  6. Previous participation in ND0612 studies.

  7. History of significant skin conditions or disorders.

ACP-103-056: A Study of the Safety and Tolerability of Pimavanserin (ACP-103) in Patients With Parkinson's Disease Psychosis

This study will evaluate the effects of an experimental drug called ACP-103 on Parkinson’s disease symptoms and on dyskinesias (involuntary movements) that develop as a result of long-term levodopa treatment. ACP-103 changes the spread of certain brain signals that are affected in patients with Parkinson’s disease.

INCLUSION CRITERIA:

Patients who meet all of the following inclusion criteria will be eligible to participate in the study:

  1. Patient is between the ages of 30 and 80 (inclusive);

  2. Patient has been diagnosed with idiopathic Parkinson’s disease based on the presence of a characteristic clinical history and neurological findings;

  3. Patient has relatively advanced disease with levodopa-associated motor response complications, including peak-dose dyskinesias and wearing-off fluctuations;

  4. Patient is willing to adhere to protocol requirements as evidenced by written, informed consent.

COMB157G2399: Long-term Safety, Tolerability and Effectiveness Study of Ofatumumab in Patients With Relapsing MS

The purpose of this study is to collect long-term safety, tolerability, effectiveness and health outcomes data in eligible subjects who have participated in a Novartis ofatumumab clinical MS study.

Vaccination sub-study The purpose of this research sub-study is to find out the effects of ofatumumab on the development of antibody responses to selected vaccines and keyhole limpet hemocyanin (KLH) neo-antigen in subjects with relapsing multiple sclerosis (RMS).

Inclusion Criteria:

  1. Must have completed a selected Novartis MS study which dosed ofatumumab 20 mg sc every 4 weeks

  2. Written informed consent

MS200527-0080: A Study of Efficacy and Safety of M2951 in Subjects With Relapsing Multiple Sclerosis

The aim of this protocol is to find out about the safety and effectiveness of M2951 in patients with relapsing multiple sclerosis. Patients will be placed into 1 of 3 groups to receive M2951, placebo or tecfidera for 24 weeks. After 24 weeks, the patients on placebo will be given M2951.

Inclusion Criteria:

  • Subjects with a diagnosis of relapsing multiple sclerosis (may include subjects with Secondary Progressive Multiple Sclerosis (SPMS) with superimposed relapses provided they meet the other criteria) in accordance with revised McDonald criteria for MS and Lublin and Reingold

  • Male or female aged 18 to 65 years

  • One or more documented relapses within the 2 years before Screening with either: a) One relapse which occurred within the last year prior to randomization or b) the presence of at least 1 Gd+ T1 lesion within 6 months prior to randomization would make the patient eligible.

  • Expanded Disability Status Scale score of 0 to 6 at Baseline

  • Women of childbearing potential must use a supplementary barrier method together with a highly effective method of contraception (according to International Council for Harmonisation [ICH] guidance M3[R2]) for 4 weeks prior to randomization, throughout the trial, and for 90 days after the last dose of IMP.

  • Signed and dated informed consent (subject must be able to understand the informed consent) indicating that the subject has been informed of all the pertinent aspects of the trial prior to enrolment and will comply with the requirements of the protocol.

CVL-865-SZ-001: A Trial of the Efficacy and Safety of CVL-865 as Adjunctive Therapy in the Treatment of Focal Onset Seizures

The purpose of this study is to assess the efficacy, safety, and tolerability profile of CVL-865 as adjunctive treatment in participants with drug-resistant focal onset seizures.

Inclusion Criteria:

  • Participants with a diagnosis of epilepsy with focal onset, as defined in the International League Against Epilepsy (ILAE) Classification of Seizures, focal aware (except participants with only focal aware seizures without a motor component), focal impaired awareness, and focal to bilateral tonic-clonic seizures for at least 2 years prior to signing the Informed Consent Form (ICF)

  • Participants must have history of an average of 4 or more spontaneous and observable focal onset, as defined in the ILAE Classification of Seizures, focal aware (except participants with only focal aware seizures without a motor component), focal impaired awareness, and focal to bilateral tonic-clonic seizures per 28-day period for at least 3 months (84 days) prior to signing the ICF

  • Participants who have tried and failed at least 2 appropriate Anti- epileptic drugs (AEDs) in the past and also currently taking 1 to 3 permitted AEDs at a stable dose for 4 Weeks prior to the Screening Visit

  • Participants with a minimum of 8 focal onset, focal aware, focal impaired awareness, or focal to bilateral tonic-clonic seizures during the 8 week baseline period with no 21-day period free of any of these seizure types

  • Participants must have had magnetic resonance imaging or contrast enhance computed tomography scan of the brain that demonstrated no progressive structural central nervous system abnormality at the time of the diagnosis of epilepsy

  • Participants must have a body mass index (BMI) of 17.5 to 40.0 kilogram per meter square (kg/m^2) and a total body weight greater than (>) 50 kilograms (kg) [110 pounds (lbs)]

  • Women of childbearing potential must agree to use an effective method of contraception from signing of informed consent throughout the duration of the study and for 30 days post last dose

  • Male must agree to use condom during treatment and until the end of relevant systemic exposure in the male participant for 94 days following the last dose with Investigational Manufacturing Product (IMP)

XPF-0A Study to Evaluate XEN1101 as Adjunctive Therapy in Focal Epilepsy

The XEN1101 Phase 2 clinical trial is a randomized, double-blind, placebo-controlled study that will evaluate the clinical efficacy, safety and tolerability of increasing doses of XEN1101 administered as adjunctive treatment in adult patients diagnosed with focal epilepsy, followed by an optional open-label extension (OLE).

Key Inclusion Criteria:

  • Be properly informed of the nature and risks of the study and give informed consent in writing, prior to entering the study

  • BMI ≤40 kg/m2

  • Diagnosis (≥2 years) of focal epilepsy according to the International League Against Epilepsy [ILAE] Classification of Epilepsy (2017)

  • Prior neuroimaging within the last 10 years and documentation is available

  • Treatment with a stable dose of 1 to 3 allowable current AEDs for at least one month prior to screening, during baseline, and throughout the duration of the DBP

  • Must be willing to comply with the contraception requirements

  • Males must agree not to donate sperm from the time of the first administration of study drug until 6 months after the last dose. Females must agree not to donate ova from the time of the first administration of study drug until 6 months after the last dose.

  • Able to keep accurate seizure diaries

Safety and Pharmacokinetic Study of YKP3089 as Adjunctive Therapy in Subjects With Partial Onset Seizures

This is a multicenter, open label study to assess the safety and pharmacokinetics of YKP3089 as adjunctive therapy in subjects with partial onset seizures. Initially, subjects taking phenytoin or phenobarbital will be enrolled followed by additional subjects taking anti-epileptic drugs other than phenytoin and phenobarbital to further investigate long-term safety.

Inclusion Criteria

  1. Male or female and greater than or equal to 18 years of age at the time of signing the informed consent. The upper age limit is 70 years inclusive.

  2. Weight at least 30 kg

  3. Written informed consent signed by the subject or legal guardian prior to entering the study in accordance with the ICH GCP guidelines. If the written informed consent is provided by the legal guardian because the subject is unable to do so, a written or verbal assent from the subject must also be obtained. In Germany, only the subject may sign the informed consent form in accordance with ICH guidelines.

  4. A diagnosis of partial epilepsy according to the International League Against Epilepsy’s Classification of Epileptic Seizures. Diagnosis should have been established by clinical history and an electroencephalogram (EEG) that is consistent with localization related epilepsy; normal interictal EEGs will be allowed provided that the subject meets the other diagnosis criterion (ie, clinical history).

  5. Have uncontrolled partial seizures and require additional AED therapy despite having been treated with at least one AED within approximately the last 2 years.

  6. Currently on stable antiepileptic treatment regimen:

    1. Subject must have been receiving stable doses of 1 to 3 AEDs for at least 3 weeks prior to Visit 2

    2. Vagal nerve stimulator (VNS) will not be counted as an AED; however, the parameters must remain stable for at least 4 weeks prior to baseline. The VNS must have been implanted at least 5 months prior to Visit 1.

    3. Benzodiazepines taken at least once per week during the 1 month prior to Visit 1 for epilepsy, or for anxiety or sleep disorder, will be counted as 1 AED and must be continued unchanged throughout the study. Therefore only a maximum of 2 additional approved AEDs will be allowed.

  7. Computed tomography (CT) or magnetic resonance imaging (MRI) scan performed within the past 10 years that ruled out a progressive cause of epilepsy. If a CT or MRI has not been performed within the past 10 years, one must be performed prior to randomization.

  8. Ability to reach subject by telephone.

  9. Use of an acceptable form of birth control by female subjects of childbearing potential

YKP3089C025: Randomized, Double-Blind Study to Evaluate Efficacy and Safety of Cenobamate Adjunctive Therapy in PGTC Seizures

This trial is intended to study the safety and effectiveness of an new anti-epileptic drug (AED) on Primary Generalized Tonic-Clonic (PGTC) Seizures. Eligible Subjects will continue to take their usual AEDs and receive either cenobamate or placebo. Subjects will have a 50% chance or receiving cenobamate or placebo (sugar pill). Subjects will initially receive 12.5 mg of cenobamate or placebo (study drug) and increase the dose every two weeks until they reach a target dose of 200 mg. Subjects will take study drug at approximately the same time in the morning (once a day) with or without food. If tolerability issues arise, dosing can be changed to evening. Also, once a subject reaches 200 mg of study drug, the dose can be decreased one time to 150 mg, if necessary. The treatment period is 22 weeks and there is a 3 week follow up period, which includes a one week decrease in study drug to 100 mg prior to stopping. Subjects who complete may be eligible for an extension study and will not have to complete the follow up period. Subjects will track their seizure types and frequency in a diary throughout the study.

Inclusion Criteria:

  1. Subject is male or female and aged ≥18 years.

  2. Written informed consent signed by the subject or legal guardian, prior to entering the study, in accordance with the International Council for Harmonisation (ICH) Good Clinical Practice (GCP) guidelines. If the written informed consent is provided by the legal guardian because the subject is unable to do so, a written or verbal assent from the subject must also be obtained. As required by country-specific regulations, only the subject may sign the Informed Consent Form (ICF) in accordance with ICH guidelines.

  3. Female subjects of childbearing potential are willing to use an acceptable form of birth control

  4. Subject has a clinical diagnosis of PGTC seizures (with or without other subtypes of generalized seizures) in the setting of idiopathic generalized epilepsy.

  5. Subject experiences at least 5 PGTC seizures in 12 weeks during the Pre-Randomization Period.

  6. Subject has had a routine electroencephalogram (EEG) within 5 years prior to Visit1 (Screening/Baseline) or during the Pre-Randomization Period with electroencephalographic features consistent with idiopathic generalized epilepsy; other concomitant anomalies must be explained by adequate past medical history.

  7. Subject has undergone computed tomography (CT) or magnetic resonance imaging (MRI) within 10 years prior to Visit 1 (Screening/Baseline) or during the Pre-Randomization Period that ruled out a progressive cause of epilepsy.

  8. Subject is currently receiving 1 to a maximum of 3 concomitant AEDs with fixed dosing regimens for a minimum of 30 days prior to Visit 1 (Screening/Baseline).

    1. Benzodiazepines (except diazepam, see Exclusion Criterion No.7) taken at least once per week during the 30 days prior to Visit 1 (Screening/Baseline) for epilepsy, anxiety, or sleep disorder will be counted as 1 AED and the dosage must be continued unchanged throughout the study. Therefore, only a maximum of 2 additional approved AEDs will be allowed. (See Exclusion Criterion No. 10 for intermittent benzodiazepine rescue parameters.)

    2. Subjects receiving felbamate as a concomitant AED must meet the following criteria: i. Have a 2-year history of felbamate use and a history of a fixed dosing regimen for a minimum of 60 days prior to Visit 1 (Screening/Baseline). ii. No prior or known history of hepatotoxicity or hematologic disorder due to felbamate.

  9. Subject with an implanted vagal nerve or deep brain stimulator will be allowed if the stimulator was implanted at least 5 months prior to Visit 1 (Screening/Baseline) and the stimulator parameters are not changed for 30 days prior to Visit 1 and for the duration of the study.

YKP3089C033: Cenobamate Open-Label Extension Study for YKP3089C025

52 Week Open-Label Safety Study of Cenobamate for Subjects who Complete YKP3089C025

Inclusion Criteria:

  • The subject must have successfully completed the Double-blind Treatment Period in the Core study.

  • Written informed consent signed by the subject or legal guardian, prior to entering the study, in accordance with the International Council for Harmonisation (ICH) Good Clinical Practice (GCP) guidelines. If the written informed consent is provided by the legal guardian because the subject is unable to do so, a written or verbal assent from the subject must also be obtained. As required by country-specific regulations, only the subject may sign the ICF in accordance with ICH guidelines.

EP0091: Study to Test the Efficacy and Safety of Padsevonil as Adjunctive Treatment of Focal-onset Seizures in Adults With Drug-resistant Epilepsy (ARISE)

The purpose of the study is to characterize the dose-response relationship with respect to efficacy of Padsevonil administered concomitantly with up to 3 anti-epileptic drugs (AEDs) for treatment of observable focal-onset seizures in subjects with drug-resistant epilepsy.

Inclusion Criteria:

  • Diagnosis of focal epilepsy per 1989 International League Against Epilepsy (ILAE) criteria at least 3 years before study entry

  • Subject has failed to achieve seizure control with 4 tolerated and appropriately chosen prior antiepileptic drugs (AED), including past and ongoing treatment, that were individually optimized for adequate dose and duration. Prior discontinued AED treatment would need to be assessed by the Investigator considering the patient medical records and patient and/or caregiver interview. ‘Prior AED’ is defined as all past and ongoing AED treatments with a start date before the Screening Visit (Visit 1)

  • Average of >= 4 spontaneous and observable focal seizures (type IA1 (i.e. focal aware), IB (i.e. focal impaired awareness), IC (i.e. focal to bilateral tonic-clonic)) per month

  • Current treatment with an individually optimized and stable dose of at least 1 and up to 3 AEDs for the 8 weeks prior to the Screening Visit with or without additional Vagus Nerve Stimulation (VNS) or other neurostimulation treatments

EP0092: A Study to Test the Efficacy and Safety of Padsevonil as Treatment of Focal-onset Seizures in Adult Subjects With Drug-resistant Epilepsy (DUET)

The purpose of the study is to evaluate the efficacy, safety and tolerability of the 3 selected dose regimens of padsevonil (PSL) administered concomitantly with up to 3 anti-epileptic drugs (AEDs) compared with placebo for treatment of observable focal-onset seizures in subjects with drug-resistant epilepsy.

Inclusion Criteria:

  • Diagnosis of focal epilepsy per 1989 International League Against Epilepsy (ILAE) criteria at least 3 years before study entry

  • Subject has failed to achieve seizure control with >=4 tolerated and appropriately chosen prior antiepileptic drugs (AED), including past and ongoing treatment, that were individually optimized for adequate dose and duration. Prior discontinued AED treatment would need to be assessed by the Investigator considering the patient medical records and patient and/or caregiver interview. ‘Prior AED’ is defined as all past and ongoing AED treatments with a start date before the Screening Visit (Visit 1)

  • Average of >= 4 spontaneous and observable focal seizures (type IA1 (i.e. focal aware), IB (i.e. focal impaired awareness), IC (i.e. focal to bilateral tonic-clonic)) per month

  • Current treatment with an individually optimized and stable dose of at least 1 and up to 3 AEDs for the 8 weeks prior to the Screening Visit with or without additional Vagus Nerve Stimulation (VNS) or other neurostimulation treatments

EP0093 :Study to Test the Safety and Efficacy of Padsevonil as Adjunctive Treatment of Focal-onset Seizures in Adult Subjects With Drug-resistant Epilepsy

The purpose of the study is to evaluate the long-term safety and tolerability of Padsevonil administered at individualized doses as adjunctive treatment for subjects with drug-resistant epilepsy.

Inclusion Criteria:

  • Subject is an adult (18 years of age or more )

  • Subject with epilepsy who has completed 1 of the previous Padsevonil (PSL) studies which allow access to the present study

  • Female subjects of child bearing potential must have a serum negative pregnancy test at the Entry Visit, which is confirmed to be negative by urine testing prior to further dispensing at each study visit thereafter. Subjects will be withdrawn from the study as soon as pregnancy is known. Female subjects will use an efficient form of contraception for the duration of the study and for a period of 3 months after their final dose of PSL.

101EP201: Phase 2 Efficacy, Safety, and Tolerability Study of Natalizumab in Focal Epilepsy (OPUS)

The primary efficacy objective of the study is to determine if adjunctive therapy of natalizumab 300 mg intravenous (IV) every 4 weeks reduces the frequency of seizures in adult participants with drug-resistant focal epilepsy. The secondary efficacy objective is to assess the effects of natalizumab versus placebo in drug-resistant focal epilepsy on additional measures of seizure frequency.

Key Inclusion Criteria:

  • Must have focal epilepsy diagnosed on clinical grounds and as applicable supported by electroencephalogram findings [Scheffer 2017] and brain imaging. Participants with multifocal epilepsy may be included if all other entry criteria are met.

  • Must have a drug-resistant epilepsy defined as failure of adequate trials of 2 (or more) tolerated and appropriately chosen and used AEDs (whether as monotherapies or in combination) [Kwan 2010].

  • Experiences 6 or more seizures during the 6-week prospective baseline period and is not seizure free for more than 21 consecutive days during the prospective baseline period

243HV101: Single-Ascending-Dose Study of BIIB076 in Healthy Volunteers and Participants With Alzheimer's Disease

The primary objective of the study is to evaluate the safety and tolerability of single-ascending intravenous (IV) infusions of BIIB076 in healthy volunteers and participants with Alzheimer’s disease (AD). A secondary objective of the study for both healthy volunteers and participants with AD is to assess the serum pharmacokinetic(s) (PK) profile of BIIB076 after single-dose administration. Another secondary objective is to evaluate the immunogenicity of BIIB076 in serum after single-dose administration.

Key Inclusion Criteria – Participants with Alzheimer’s Disease (AD)

  • Must meet all of the clinical criteria for mild cognitive impairment (MCI) due to AD or mild AD according to the National Institutes of Aging-Alzheimer’s Association [McKhann 2011], and in addition must have the following:

  • Clinical Dementia Rating (CDR) global score of 0.5 for MCI due to AD or 0.5 or 1 for mild AD.

  • CDR Memory Box Score of ≥0.5.

  • Mini-Mental State Examination score between 18 and 30 (inclusive) at Screening.

  • Must have amyloid beta positivity confirmed at Screening

BAN2401-G000-301: A Study to Confirm Safety and Efficacy of BAN2401 in Participants With Early Alzheimer's Disease (Clarity AD)

This study will be conducted to evaluate the efficacy of BAN2401 in participants with early Alzheimer’s disease (EAD) by determining the superiority of BAN2401 compared with placebo on the change from baseline in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) at 18 months of treatment in the Core Study. This study will also evaluate the long-term safety and tolerability of BAN2401 in participants with EAD in the Extension Phase and whether the long-term effects of BAN2401 as measured by the CDR-SB at the end of the Core Study is maintained over time in the Extension Phase.

Diagnosis: Mild Cognitive Impairment (MCI) due to Alzheimer’s disease – intermediate likelihood:

  • Meet the National Institute of Aging – Alzheimer’s Association (NIA-AA) core clinical criteria for MCI due to Alzheimer’s disease – intermediate likelihood

  • Have a global Clinical Dementia Rating (CDR) score of 0.5 and CDR Memory Box score of 0.5 or greater at Screening and Baseline

  • Report a history of subjective memory decline with gradual onset and slow progression over the last 1 year before Screening; must be corroborated by an informant

Mild Alzheimer’s disease dementia:

  • Meet the NIA-AA core clinical criteria for probable Alzheimer’s disease dementia

  • Have a global CDR score of 0.5 to 1.0 and a CDR Memory Box score of 0.5 or greater at Screening and Baseline

CNP520A2202J : A Study of CNP520 Versus Placebo in Participants at Risk for the Onset of Clinical Symptoms of Alzheimer's Disease (Generation S2)

The purpose of this study is to determine the effects of CNP520 on cognition, global clinical status, and underlying AD pathology, as well as the safety of CNP520, in people at risk for the onset of clinical symptoms of AD based on their age, APOE genotype and elevated amyloid.

Inclusion Criteria:

  • consent to receive disclosure of their risk estimates to develop clinical symptoms of AD based on their APOE genotype and, if Heterozygotes, evidence of elevated brain amyloid.

  • Male or female, age 60 to 75 years inclusive. Females must be considered post-menopausal and not of child bearing potential

  • Cognitively unimpaired as evaluated by memory tests performed at screening.

  • Participant’s willingness to have a study partner.

  • Carrier of at least one APOE4 gene if Heterozygotes, elevated brain amyloid (as measured by CSF Abeta or amyloid PET imaging).

E2609- 301-302: A 24-Month Study to Evaluate the Efficacy and Safety of Elenbecestat (E2609) in Subjects With Early Alzheimer's Disease (MissionAD1)

The name of this trial is MissionAD1. This phase 3 study consists of a Core and Open Label Extension (OLE) Phase in participants with Early Alzheimer’s Disease (EAD), and will be conducted to evaluate the efficacy and safety of E2609. The Core is a 24-month treatment, multicenter, double blind, placebo controlled parallel group study. The OLE is a 24-month treatment, one group study. The data for end points for the studies E2609-G000-301 (NCT02956486) and E2609-G000-302 (NCT03036280) will be pooled for a combined total of 1900 participants.

Inclusion Criteria:

Core Study

  • Mild cognitive impairment due to AD or mild AD dementia including

    1. MMSE score equal to or greater than 24

    2. CDR global score of 0.5

    3. CDR Memory Box score of 0.5 or greater

  • Impaired episodic memory confirmed by a list learning task

  • Positive biomarker for brain amyloid pathology as indicated by either amyloid PET or cerebrospinal fluid AD assessment or both

ID-078-302: Study to Assess the Efficacy and Safety of ACT-541468 in Adult and Elderly Subjects Suffering From Difficulties to Sleep

The main purpose of this Phase 3 study is to evaluate the efficacy of 10 mg and 25 mg ACT-541468 on objective sleep parameters in subjects with insomnia disorder.

Inclusion Criteria:

  • Signed informed consent prior to any study-mandated procedure;

  • Male or female aged ≥ 18 years;

  • Insomnia disorder according to DSM-5 criteria;

  • Insomnia Severity Index score ≥ 15;

  • Insufficient sleep quantity as collected subjectively in the sleep diary and validated objectively by polysomnography;

  • Women of childbearing potential must have a negative and urine pregnancy test and use the contraception scheme up to at least 30 days after last study treatment intake.

42-1703: Safety and Tolerability Study of Diazepam Buccal Soluble Film (DBSF) in Subjects With Epilepsy (DBSF)

This Phase 3, multicenter, open-label study of chronic, intermittent use of study drug (DBSF) is designed to evaluate the safety and tolerability of the buccal formulation of diazepam in children, adolescents and adults with acute repetitive seizures.

Inclusion Criteria:

  1. Female or male subject between the ages of 2 and 65 years of age, inclusive

  2. Written informed consent to participate in the study

  3. Subject has an established diagnosis of epilepsy either partial or generalized epilepsy with motor seizures with clear alteration of awareness, and while on a regimen of anti-epileptic medication(s), still experiences bouts of seizures (frequent break through seizures, e.g. ARS or seizure clusters) and who, in the opinion of the Investigator, may need benzodiazepine intervention for seizure control at least 1 time a month on average.

  4. Caregiver, if needed for subject, provides written informed consent and is able to administer study drug in the event of a seizure.

  5. Female subjects ≥12 years of age have a negative serum pregnancy test at screening. Female subjects of childbearing potential, (not surgically sterile or less than 2 years postmenopausal), must have a partner who is sterile, agrees to abstinence, be practicing double barrier contraception or using an FDA approved contraceptive (e.g., licensed hormonal or barrier methods) for greater than 2 months prior to screening visit and commit to an acceptable form of birth control for the duration of the study and for 30 days after the study

  6. No aspects of the medical history and/or the physical-neurological examination that at the judgment of the Investigator, in consultation with the Sponsor, will interfere with administration or absorption of study drug, or could evolve into a safety issue

  7. No clinically significant abnormal findings on the electrocardiogram (QTcF≤450 msec for males and QTcF≤470 msec for females)

  8. Subject and caregiver must be willing to comply with all study visits and all required study procedures

DIAZ.001.05: Repeat Dose Safety Study of NRL-1 in Epilepsy Subjects

This is a 12 month safety study to evaluate the safety of repeated doses of NRL-1

 

Inclusion Criteria:

  1. Male and female subjects between the ages of 6 and 65 years, inclusive.

  2. Written informed consent to participate in the study.

  3. Subject has a clinical diagnosis of Epilepsy and while on a stable regimen of anti-epileptic medication, still experiences bouts of seizures (e.g. frequent break through seizures or Acute Repetitive Seizures [ARS]), and who, in the opinion of the Investigator, may need benzodiazepine intervention for seizure control at least 1 time a month on average.

  4. Subject has a qualified caregiver or medical professional available that can administer study medication in the event of a seizure.

  5. Subjects having either partial or generalized Epilepsy with motor seizures or seizures with clear alteration of awareness.

  6. Female subjects of childbearing potential, defined as having a menstrual cycle and who are not surgically sterile or less than two (2) years postmenopausal, must complete a pregnancy screen and agree to utilize one of the following forms of contraception during the trial and for 21 days after the last dose of study drug: abstinence, hormonal (oral, transdermal, implant, or injection), barrier (condom, diaphragm with spermicide), intrauterine device (IUD), or vasectomized partner (six months minimum). Subjects must have used the same method for at least one (1) month prior to starting the study.

  7. No clinically significant abnormal findings in the medical history, on the physical examination or electrocardiogram (QTcF<450 msec for males and QTcF<470 msec for females).

  8. Subjects and caregivers must agree to return to the study site for all study visits and must be willing to comply with all required study procedures.

Cenobamate Adjunctive Therapy in PGTC Seizures

This trial is intended to study the safety and effectiveness of an new anti-epileptic drug (AED) on Primary Generalized Tonic-Clonic (PGTC) Seizures. Eligible Subjects will continue to take their usual AEDs and receive either cenobamate or placebo. Subjects will have a 50% chance or receiving cenobamate or placebo (sugar pill). Subjects will initially receive 12.5 mg of cenobamate or placebo (study drug) and increase the dose every two weeks until they reach a target dose of 200 mg. Subjects will take study drug at approximately the same time in the morning (once a day) with or without food. If tolerability issues arise, dosing can be changed to evening. Also, once a subject reaches 200 mg of study drug, the dose can be decreased one time to 150 mg, if necessary. The treatment period is 22 weeks and there is a 3 week follow up period, which includes a one week decrease in study drug to 100 mg prior to stopping. Subjects who complete may be eligible for an extension study and will not have to complete the follow up period. Subjects will track their seizure types and frequency in a diary throughout the study.

Inclusion Criteria:
Subject is male or female and aged ≥18 years.
Written informed consent signed by the subject or legal guardian
Subject has a clinical diagnosis of PGTC seizures
Subject experiences at least 3 PGTC seizures in 12 weeks during the Pre-Randomization Period.
Subject has had a routine electroencephalogram (EEG) within 5 years prior to Visit1
Subject has undergone computed tomography (CT) or magnetic resonance imaging (MRI) within 10 years prior to Visit 1
Subject is currently receiving 1 to a maximum of 3 concomitant AEDs with fixed dosing regimens for a minimum of 30 days prior to Visit 1
Subject with an implanted vagal nerve or deep brain stimulator will be allowed if the stimulator was implanted at least 5 months prior to Visit 1.
Subject taking a ketogenic diet will be allowed as long as the diet has been stable for at least 3 months prior to Visit 1

XEN1101 as Adjunctive Therapy in Focal Epilepsy

The XEN1101 Phase 2 clinical trial is a randomized, double-blind, placebo-controlled study that will evaluate the clinical efficacy, safety and tolerability of increasing doses of XEN1101 administered as adjunctive treatment in adult patients diagnosed with focal epilepsy.

Inclusion Criteria:
Patient must be 18 Years to 75 Years old.
Be properly informed of the nature and risks of the study and give informed consent in writing, prior to entering the study
BMI <35 kg/m2
Diagnosis (≥2 years) of focal epilepsy according to the International League Against Epilepsy [ILAE] Classification of Epilepsy (2017)
Treatment with a stable dose of 1 to 3 allowable current AEDs for at least one month prior to screening, during baseline, and throughout the duration of the study
Must be willing to comply with the contraception requirements
Able to keep accurate seizure diaries

Long-term Safety, Tolerability and Effectiveness Study of Ofatumumab in Patients With Relapsing MS

The purpose of this study is to collect long-term safety, tolerability, effectiveness and health outcomes data in eligible subjects who have participated in a Novartis ofatumumab clinical MS study.

Inclusion Criteria:
Patient must be 18 Years and older
Must have completed a selected Novartis MS study which dosed ofatumumab 20 mg sc every 4 weeks
Written informed consent

ACP-103 to Treat Parkinson's Disease

This study will evaluate the effects of an experimental drug called ACP-103 on Parkinson’s disease symptoms and on dyskinesias (involuntary movements) that develop as a result of long-term levodopa treatment. ACP-103 changes the spread of certain brain signals that are affected in patients with Parkinson’s disease.

Inclusion Criteria:
Patient must be between the ages of 30 and 80 (inclusive)
Patient has been diagnosed with idiopathic Parkinson’s disease based on the presence of a characteristic clinical history and neurological findings
Patient has relatively advanced disease with levodopa-associated motor response complications, including peak-dose dyskinesias and wearing-off fluctuations.
Patient is willing to adhere to protocol requirements as evidenced by written, informed consent.

BAN2401 CLARITY IV MonoconalAb

This study will be conducted to evaluate the efficacy of BAN2401 in participants with early Alzheimer’s disease (EAD) by determining the superiority of BAN2401 compared with placebo on the change from baseline in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) at 18 months of treatment in the Core Study. This study will also evaluate the long-term safety and tolerability of BAN2401 in participants with EAD in the Extension Phase.

Inclusion Criteria:
Must be 50 Years to 90 Years old
Diagnosis of Mild Cognitive Impairment (MCI) due to Alzheimer’s disease
Diagnosis of  Mild Alzheimer’s disease dementia
Objective impairment in episodic memory as indicated by at least 1 standard deviation below age-adjusted mean in the Wechsler Memory Scale IV-Logical Memory (subscale) II (WMS-IV LMII)
Positive biomarker for brain amyloid pathology
Male or female participants aged greater than or equal to (>=)50 and <=90 years, at the time of informed consent
Mini mental state examination (MMSE) score greater than or equal to 22 at Screening and Baseline and less than or equal to 30 at Screening and Baseline
Body mass index (BMI) greater than 17 and less than 35 at Screening
If receiving an approved Alzheimer’s disease treatment such as acetylcholinesterase inhibitor (AChEIs) or memantine or both for Alzheimer’s disease, must be on a stable dose for at least 12 weeks prior to Baseline. Treatment-naïve participants for Alzheimer’s disease can be entered into the study. Unless otherwise stated, participants must have been on stable doses of all other (ie, non-Alzheimer’s disease-related) permitted concomitant medications for at least 4 weeks prior to Baseline.

Elebesestat (E2609) MISSIONAD2- BACE Inhibitor (MCI & Early AD)

The name of this trial is MissionAD2. This phase 3 study consists of a Core and Open Label Extension (OLE) Phase in participants with Early Alzheimer’s Disease (EAD), and will be conducted to evaluate the efficacy and safety of E2609. The Core is a 24-month treatment, multicenter, double blind, placebo controlled parallel group study. The OLE is a 24-month treatment, one group study. The data for end points for the studies E2609-G000-301 (NCT02956486) and E2609-G000-302 (NCT03036280) will be pooled.

Inclusion Criteria:
Must be 50 Years to 85 Years old
Mild cognitive impairment due to AD or mild AD dementia including
1. MMSE score equal to or greater than 24
2. CDR global score of 0.5
3. CDR Memory Box score of 0.5 or greater
Impaired episodic memory confirmed by a list learning task
Positive biomarker for brain amyloid pathology as indicated by either amyloid PET or CSF AD assessment or both

CNP 520(Generations 2)

The purpose of this study is to determine the effects of CNP520 on cognition, global clinical status, and underlying AD pathology, as well as the safety of CNP520, in people at risk for the onset of clinical symptoms of AD based on their age, APOE genotype and elevated amyloid.

Inclusion Criteria:
Consent to receive disclosure of their risk estimates to develop clinical symptoms of AD based on their APOE genotype and, if Heterozygotes, evidence of elevated brain amyloid.
Male or female, age 60 to 75 years inclusive. Females must be considered post-menopausal and not of child bearing potential
Cognitively unimpaired as evaluated by memory tests performed at screening.
Participant’s willingness to have a study partner.
Carrier of at least one APOE4 gene if Heterozygotes, elevated brain amyloid (as measured by CSF Abeta or amyloid PET imaging).

BIIB076 Novel TAU binding- humanized Monoclonal Antibodies

The primary objective of the study is to evaluate the safety and tolerability of single-ascending intravenous (IV) infusions of BIIB076 in healthy volunteers and participants with Alzheimer’s disease (AD). A secondary objective of the study for both healthy volunteers and participants with AD is to assess the serum pharmacokinetic(s) (PK) profile of BIIB076 after single-dose administration. Another secondary objective is to evaluate the immunogenicity of BIIB076 in serum after single-dose administration.

Inclusion Criteria:
Must be 50 Years to 80 Years of age

Healthy Participants
Must be in good health as determined by the Investigator, based on medical history and Screening evaluations.

Participants with Alzheimer’s Disease (AD)
Must meet all of the clinical criteria for mild cognitive impairment (MCI) due to AD or mild AD according to the National Institutes of Aging-Alzheimer’s Association [McKhann 2011], and in addition must have the following:
Clinical Dementia Rating (CDR) global score of 0.5 for MCI due to AD or 0.5 or 1 for mild AD.
CDR Memory Box Score of ≥0.5.
Mini-Mental State Examination score between 18 and 30 (inclusive) at Screening.
Must have amyloid beta positivity confirmed at Screening

OPUS Study of Natalizumab in Focal Epilepsy

The primary efficacy objective of the study is to determine if adjunctive therapy of natalizumab 300 mg intravenous (IV) every 4 weeks reduces the frequency of seizures in adult participants with drug-resistant focal epilepsy. The secondary efficacy objective is to assess the effects of natalizumab versus placebo in drug-resistant focal epilepsy on additional measures of seizure frequency.

Inclusion Criteria:
Clinical diagnosis of focal epilepsy, supported by electroencephalogram
Drug-resistant epilepsy, defined as failure of adequate trials of 2 or more antiepileptic drugs
Must have 6 or more seizure during the 6-week baseline period
Must not be seizure free for more than 21 consecutive days

ARISE Study on Padsevonil as Adjunctive Treatment of Focal-Onset Seizures in Adult with Drug-resistant Epilepsy

The purpose of the study is to characterize the dose-response relationship with respect to efficacy of Padsevonil administered concomitantly with up to 3 anti-epileptic drugs (AEDs) for treatment of observable focal-onset seizures in subjects with drug-resistant epilepsy.

Inclusion Criteria:
Diagnosis of focal epilepsy at least 3 years before study entry
Failed to control seizure with 4 antiepileptic drugs previously
4 or more spontaneous and observable focal seizures per month

Repeat Dose Safety Study of NRL-1 in Epilepsy Subjects

This is a 12-month safety study to evaluate the safety of repeated doses of NRL-1

Inclusion Criteria:
6 to 65 years old
Clinical diagnosis of epilepsy and while on antiepileptic medication still experiences seizures
Have partial or generalized Epilepsy with motor seizures and seizures with clear alternation of awareness

YKP3089C021 Study on Partial Onset Seizures.

This is a multicenter, open label study to assess the safety and pharmacokinetics of YKP3089 as adjunctive therapy in subjects with partial onset seizures. Initially, subjects taking phenytoin or phenobarbital will be enrolled followed by additional subjects taking anti-epileptic drugs other than phenytoin and phenobarbital to further investigate long-term safety.

Inclusion Criteria:
18 to 70 years old at least 30 kg weight
Diagnosis of partial epilepsy demonstrated in clinical history or EEG
Uncontrolled partial seizures that require additional AED therapy despite current medication
Currently on stable antiepileptic treatment regimen
CT or MRI scan performed prior to randomization up to 10 years that rules out progressive cause of epilepsy

COMB157G2301 Study on Relapsing Remitting Multiple Sclerosis

A clinical study to compare the efficacy and safety of Ofatumumab administered subcutaneously every 4 weeks versus Teriflunomide administered orally once daily in patients with relapsing multiple sclerosis (MS).

Inclusion Criteria:
Ages 18 to 55 years old
Clinical diagnosis of Multiple Sclerosis
Relapsing-Remitting Multiple Sclerosis and Secondary Progressive Multiple Sclerosis course
At least 1 relapse during the previous year or 2 relapses during the past 2 years or a positive Gadolinium-enhanced MRI scan in the previous year
Expanded Disability Status Scale of 0 to 5.5