Study of BHV-4157 in Alzheimer's Disease (T2 Protect AD)

November 14, 2023 updated by: Biohaven Pharmaceuticals, Inc.

A Phase 2 Randomized Double-Blind Placebo-Controlled Trial to Evaluate the Efficacy and Safety of BHV-4157 in Patients With Mild to Moderate Alzheimer's Disease

Preclinical models suggest that riluzole, the active metabolite of BHV-4157, may protect from AD-related pathology and cognitive dysfunction. Titrated dose of BHV-4157 to 280 mg, or placebo, were administered orally once daily. Duration of treatment is 48 weeks in double-blind phase. There is also a screening period of up to 42 days; and a 4-week post-treatment observation period. Eligible participants who completed the double-blind treatment phase had the opportunity to receive open-label troriluzole for up to 48 weeks in an open-label extension (OLE) phase.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
350

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85013
        • Barrow Neurological Institute
      • Phoenix, Arizona, United States, 85004
        • Xenoscience, Inc.
      • Sun City, Arizona, United States, 85351
        • Banner Sun Health Research Institute
    • California
      • Fullerton, California, United States, 92835
        • Neurology Center of North Orange County
      • La Jolla, California, United States, 92037
        • University of California, San Diego
      • Los Angeles, California, United States, 90033
        • University of Southern California
      • Pasadena, California, United States, 91105
        • SC3 Research Group - Pasadena
    • Connecticut
      • Hamden, Connecticut, United States, 06518
        • Geriatric and Adult Psychiatry
      • New Haven, Connecticut, United States, 06510
        • Yale University School of Medicine
      • Stamford, Connecticut, United States, 06905
        • Ki Health Partners LLC DBA New England Institute for Clinical Research
    • Florida
      • Delray Beach, Florida, United States, 33445
        • Brain Matters Research
      • Miami, Florida, United States, 33136
        • University of Miami
      • Tampa, Florida, United States, 33613
        • USF Health Byrd Alzheimer's Institute
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
      • Chicago, Illinois, United States, 60640
        • Great Lakes Clinical Trials
      • Springfield, Illinois, United States, 62702
        • Southern Illinois University
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa
    • Kentucky
      • Lexington, Kentucky, United States, 40504
        • University of Kentucky
    • Louisiana
      • Baton Rouge, Louisiana, United States, 70808
        • Pennington Biomedical Research Center
    • Maine
      • Bangor, Maine, United States, 04401
        • Northern Light Acadia Hospital
    • Maryland
      • Baltimore, Maryland, United States, 21224
        • Johns Hopkins University
    • Michigan
      • Ann Arbor, Michigan, United States, 48105
        • University of Michigan, Ann Arbor
      • East Lansing, Michigan, United States, 48824
        • Michigan State University
    • Missouri
      • Chesterfield, Missouri, United States, 63005
        • Galen Research
    • Nevada
      • Las Vegas, Nevada, United States, 89106
        • Cleveland Clinic Lou Ruvo Center
    • New Jersey
      • Princeton, New Jersey, United States, 08540
        • Princeton Medical Institute
    • New York
      • Bronx, New York, United States, 10468
        • James J. Peters VAMC
      • New York, New York, United States, 10032
        • Columbia University
      • Rochester, New York, United States, 14620
        • University of Rochester Medical Center
      • Syracuse, New York, United States, 13202
        • SUNY Upstate Medical University Department of Geriatrics
    • Ohio
      • Beachwood, Ohio, United States, 44122
        • Case Western Reserve University
      • Columbus, Ohio, United States, 43210
        • Ohio State University
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74104
        • Tulsa Clinical Research
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University
    • Pennsylvania
      • Norristown, Pennsylvania, United States, 19403
        • Keystone Clinical Studies, LLC
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh
      • Wilkes-Barre, Pennsylvania, United States, 18711
        • Geisinger Medical Clinic
      • Willow Grove, Pennsylvania, United States, 19090
        • Abington Neurological Associates
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Rhode Island Hospital
    • South Carolina
      • Charleston, South Carolina, United States, 29401
        • CBRI, Roper Hospital
    • Tennessee
      • Nashville, Tennessee, United States, 37212
        • Vanderbilt Memory & Alzheimer's Center
    • Texas
      • San Antonio, Texas, United States, 78229-3900
        • The Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases,University of Texas Health Science Center at San Antonio
    • Washington
      • Seattle, Washington, United States, 98108
        • University of Washington

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

50 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  • Age 50 to 85 (inclusive) at screening
  • Diagnosed with probable Alzheimer's disease dementia: Core clinical criteria in accordance with NIA/Alzheimer's Association Guidelines.
  • Living in the community (includes assisted living facilities, but excludes long-term care nursing facilities).
  • Ambulatory, or able to walk with an assistive device, such as a cane or walker.
  • Participants must have a study partner who has frequent interaction with them (approximately >3-4 times per week), will be present for all clinic visits, and can assist in compliance with study procedures.
  • An Mini-Mental State Examination score of 14 to 24, inclusive, at screening.
  • A brain MRI scan within 6 months of screening consistent with a diagnosis of Alzheimer's disease.
  • Participants should be treated with a stable dosage regimen of FDA-approved AD medications (acetylcholinesterase inhibitors (AchEI) and/or memantine) for at least 3 months prior to screening. Participants should be expected to remain on a stable dosage regimen of these medications for the duration of the trial.
  • Participants who are not being treated with FDA-approved AD medications at the time of screening, because they have contraindications to these medications, or because they have previously failed treatment with these medications, are also eligible for inclusion, if it is expected that they will not be treated with these medications for the duration of the trial.

Key Exclusion Criteria:

  • Hepatic impairment defined as Child-Pugh class of A or more severe liver impairment.
  • Other neurodegenerative diseases and causes of dementias, including Parkinson's disease and Huntington's disease, vascular dementia, CJD (Creutzfeldt-Jakob disease), LBD (Lewy Body dementia), PSP (Progressive Supranuclear Palsy), AIDS (Acquired Immunodeficiency Syndrome), or NPH (normal pressure hydrocephalus).
  • History of a major depressive episode within the past 6 months of screening.
  • Insulin-dependent diabetes or uncontrolled diabetes with HbA1c value >8.0 %.
  • Cancer or a malignant tumor within the past 3 years, except patients who underwent potentially curative therapy with no evidence of recurrence for >3 years. Patients with stable prostate cancer or non-melanoma skin cancers are not excluded.
  • Participation in another clinical trial for an investigational agent and having taken at least one dose of study medication, unless confirmed as having been on placebo, within 12 weeks prior to screening. The end of a previous investigational trial is defined as the date of the last dose of an investigational agent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: BHV-4157
troriluzole, 280 mg (2 x 140 mg) capsules, QD
Drug: troriluzole
Oral BHV-4157 will be given daily for up to 48 weeks
Other Names:
  • BHV-4157
Placebo Comparator: Placebo
matching 280 mg (2 x 140 mg) placebo capsules, QD
Drug: Placebo oral capsule
Oral matching placebo will be given daily for up to 48 weeks

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Total Score at Week 48
Time Frame: Baseline (Day 1) and Week 48
The ADAS-Cog is a structured scale that evaluates memory (word recall, word recognition), reasoning (following commands), language (naming, comprehension), orientation, ideational praxis (placing a letter in an envelope) and constructional praxis (copying geometric designs). Ratings of spoken language, language comprehension, word finding difficulty, and ability to remember test instructions were also obtained. The test was scored in terms of errors on a scale ranging from 0 (best) to 70 (worse), with higher scores indicate poorer performance and greater impairment.
Baseline (Day 1) and Week 48
Change From Baseline in Clinical Dementia Rating-Sum of Boxes (CDR-Sum of Boxes) Total Score at Week 48
Time Frame: Baseline (Day 1) and Week 48
The CDR-sum of boxes is a validated composite rating of cognition and everyday functioning used in longitudinal AD research which incorporates both informant input and direct assessment of performance. It assesses through semi-structured interview 3 cognitive domains including memory, orientation, and judgement/problem solving and 3 everyday functional domains including community affairs, home and hobbies and personal care. The individual domain score ranging from 0 (none) to 3 (severe) but the scores in each of these were combined to obtain a composite score (sum of boxes) ranging from 0 (best) to 18 (worst), with higher scores indicate poorer performance and greater impairment. The individual domain scores are added to create a sum of the box scores.
Baseline (Day 1) and Week 48

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change From Baseline in Magnetic Resonance Imaging (MRI) Hippocampal Volume at Week 48
Time Frame: Baseline (Day 1) and Week 48
Volumetric MRI allows the in vivo assessment of brain structure volume and provides a measure of atrophy rate. Results from MRI studies suggest that the patterns of atrophy in AD, which mirror the pathological progression of the disease, can reliably be detected and tracked across time. Hippocampal volume derived from MRI correlates with histological hippocampal volume and degree of neuronal loss and AD pathology, and entorhinal cortical thickness change appears to be an early and sensitive indicator of neurodegeneration associated with AD.
Baseline (Day 1) and Week 48
Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Total Score at Week 48
Time Frame: Baseline (Day 1) and Week 48
The ADCS-ADL inventory scale is validated questionnaire developed by the ADCS to assess instrumental and basic activities of daily living based on a 23-item structured interview of the AD study participant's partner. The scale ranging from 0 (none) to 78 (severe), with lower scores indicate greater impairment.
Baseline (Day 1) and Week 48
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Week 48
Time Frame: Baseline (Day 1) and Week 48
The NPI is a well-validated, reliable, multi-item instrument to assess psychopathology in AD dementia based on the results of an interview with the study partner. The NPI evaluates both the frequency and severity of 10 neuropsychiatric features, including delusions, hallucinations, agitation/aggression, dysphoria, anxiety, euphoria, apathy, disinhibition, irritability and lability, and aberrant motor behavior, as well as evaluates sleep and appetite/eating disorders. Frequency assessments range from 1 (occasionally, less than once per week) to 4 (very frequently, once or more per day or continuously). Severity assessments range from 1 (mild) to 3 (severe). The total score is the sum of all subscales ranging from 1 (mild) to 7 (severe), with higher scores indicate greater impairment.
Baseline (Day 1) and Week 48
Change From Baseline in Mini-Mental Status Examination (MMSE) Total Score at Week 48
Time Frame: Baseline (Day 1) and Week 48
The MMSE is a frequently used screening instrument for AD drug studies. It evaluates orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy 2 intersecting pentagons. The MMSE scale ranging from 0 (worse) to 30 (best), with a lower score indicate more cognitive impairment.
Baseline (Day 1) and Week 48
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
Time Frame: TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks.
An adverse event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in participants or clinical investigation participants administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. A serious AE (SAE) is defined as any event that met any of the following criteria at any dose: death; life-threatening; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect in the offspring of a participant who received study drug; other important medical events that may have jeopardized the participant and may have required medical or surgical intervention to prevent one of the other serious outcomes. An AE is considered "Related" for causality designations of possible, probable and definite.
TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks.

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change From Baseline in Magnetic Resonance Imaging (MRI) Hippocampal Volume at Week 48 in Mild Subgroup
Time Frame: Baseline (Day 1) and Week 48
Subgroup of participants MMSE Category = Mild. The MMSE scale ranging from 0 (worse) to 30 (best), with a lower score indicating more cognitive impairment. Mild are participants with a baseline MMSE score greater than or equal to 20.
Baseline (Day 1) and Week 48

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Biohaven Pharmaceuticals, Inc.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Alzheimer's Disease Cooperative Study (ADCS)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 31, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 15, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 23, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 23, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 27, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 30, 2018

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 6, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 14, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • BHV4157-203

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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