Study of BHV-4157 in Alzheimer's Disease

NCT03605667 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: BHV4157-203
• Study Type: interventional
• Target: 350
• Locations: 1 country
• Sites: 44

Brief Summary

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.

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Total Score at 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

  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 Outcomes (5)

• Change From Baseline in Magnetic Resonance Imaging (MRI) Hippocampal Volume at Week 48

  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

  Baseline (Day 1) and Week 48

• Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Week 48

  Baseline (Day 1) and Week 48

• Change From Baseline in Mini-Mental Status Examination (MMSE) Total Score at Week 48

  Baseline (Day 1) and Week 48

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs

  TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks.

Other Outcomes (1)

• Change From Baseline in Magnetic Resonance Imaging (MRI) Hippocampal Volume at Week 48 in Mild Subgroup

  Baseline (Day 1) and Week 48

Study Arms (2)

BHV-4157

EXPERIMENTAL

troriluzole, 280 mg (2 x 140 mg) capsules, QD

Drug: troriluzole

Placebo

PLACEBO COMPARATOR

matching 280 mg (2 x 140 mg) placebo capsules, QD

Drug: Placebo oral capsule

Interventions

troriluzole DRUG

Oral BHV-4157 will be given daily for up to 48 weeks

Also known as: BHV-4157

BHV-4157

Placebo oral capsule DRUG

Oral matching placebo will be given daily for up to 48 weeks

Placebo

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Biohaven Pharmaceuticals, Inc.: lead
• Alzheimer's Disease Cooperative Study (ADCS): collaborator

Study Sites (44)

Xenoscience, Inc.

Phoenix, Arizona, 85004, United States

Location

Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

Location

Banner Sun Health Research Institute

Sun City, Arizona, 85351, United States

Location

Neurology Center of North Orange County

Fullerton, California, 92835, United States

Location

University of California, San Diego

La Jolla, California, 92037, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

SC3 Research Group - Pasadena

Pasadena, California, 91105, United States

Location

Geriatric and Adult Psychiatry

Hamden, Connecticut, 06518, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06510, United States

Location

Ki Health PARTNERS LLC DBA NEW ENGLAND INSTITUTE FOR CLINICAL RESEARCH

Stamford, Connecticut, 06905, United States

Location

Brain Matters Research

Delray Beach, Florida, 33445, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

USF Health Byrd Alzheimer's Institute

Tampa, Florida, 33613, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Great Lakes Clinical Trials

Chicago, Illinois, 60640, United States

Location

Southern Illinois University

Springfield, Illinois, 62702, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Kentucky

Lexington, Kentucky, 40504, United States

Location

Pennington Biomedical Research Center

Baton Rouge, Louisiana, 70808, United States

Location

Northern Light Acadia Hospital

Bangor, Maine, 04401, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21224, United States

Location

University of Michigan, Ann Arbor

Ann Arbor, Michigan, 48105, United States

Location

Michigan State University

East Lansing, Michigan, 48824, United States

Location

Galen Research

Chesterfield, Missouri, 63005, United States

Location

Cleveland Clinic Lou Ruvo Center

Las Vegas, Nevada, 89106, United States

Location

Princeton Medical Institute

Princeton, New Jersey, 08540, United States

Location

Columbia University

New York, New York, 10032, United States

Location

University of Rochester Medical Center

Rochester, New York, 14620, United States

Location

SUNY Upstate Medical University Department of Geriatrics

Syracuse, New York, 13202, United States

Location

James J. Peters VAMC

The Bronx, New York, 10468, United States

Location

Case Western Reserve University

Beachwood, Ohio, 44122, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Tulsa Clinical Research

Tulsa, Oklahoma, 74104, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Keystone Clinical Studies, LLC

Norristown, Pennsylvania, 19403, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Geisinger Medical Clinic

Wilkes-Barre, Pennsylvania, 18711, United States

Location

Abington Neurological Associates

Willow Grove, Pennsylvania, 19090, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

CBRI, Roper Hospital

Charleston, South Carolina, 29401, United States

Location

Vanderbilt Memory & Alzheimer's Center

Nashville, Tennessee, 37212, United States

Location

The Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases,University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229-3900, United States

Location

University of Washington

Seattle, Washington, 98108, United States

Location

Related Publications (1)

• Qiu Y, Jacobs DM, Messer K, Salmon DP, Wellington CL, Stukas S, Revta C, Brewer JB, Leger GC, Askew B, Donahue L, Kaplita S, Coric V, Qureshi IA, Feldman HH; Alzheimer's Disease Cooperative Study T2 Protect AD Study Group. Prognostic value of plasma biomarkers for informing clinical trial design in mild-to-moderate Alzheimer's disease. Alzheimers Res Ther. 2025 May 2;17(1):97. doi: 10.1186/s13195-025-01745-3.

  PMID: 40317057 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Limitations and Caveats

All participants in the OLE phase underwent a termination visit 2 weeks after the last dose of troriluzole.

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Biohaven Pharmaceuticals, Inc

clinicaltrials@biohavenpharma.com

+1 203-404-0410

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2018
• First Posted: July 30, 2018
• Study Start: July 31, 2018
• Primary Completion: December 15, 2020
• Study Completion: December 23, 2021
• Last Updated: December 6, 2023
• Results First Posted: December 6, 2023

Record last verified: 2023-11

Locations

US (44)