Clinical trial NCT03605667: Study of BHV-4157 in Alzheimer's Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alzheimer Disease
Lead sponsor: Biohaven Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Alzheimer's Disease Cooperative Study (ADCS)
First posted: 2018-07-30
Enrollment: 350
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Total Score at Week 48
timeFrame: Baseline (Day 1) and Week 48
measure: Change From Baseline in Clinical Dementia Rating-Sum of Boxes (CDR-Sum of Boxes) Total Score at Week 48
timeFrame: Baseline (Day 1) and Week 48
Secondary outcomes:
measure: Change From Baseline in Magnetic Resonance Imaging (MRI) Hippocampal Volume at Week 48
timeFrame: Baseline (Day 1) and Week 48
measure: Change From Baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Total Score at Week 48
timeFrame: Baseline (Day 1) and Week 48
measure: Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Week 48
timeFrame: Baseline (Day 1) and Week 48
measure: Change From Baseline in Mini-Mental Status Examination (MMSE) Total Score at Week 48
timeFrame: Baseline (Day 1) and Week 48
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
timeFrame: TEAEs were reported from first dose of study drug up to end of study treatment, maximum of 96 weeks.
Other outcomes:
measure: Change From Baseline in Magnetic Resonance Imaging (MRI) Hippocampal Volume at Week 48 in Mild Subgroup
timeFrame: Baseline (Day 1) and Week 48
Locations:
city: Phoenix
country: United States
facility: Xenoscience, Inc.
state: Arizona
city: Phoenix
country: United States
facility: Barrow Neurological Institute
state: Arizona
city: Sun City
country: United States
facility: Banner Sun Health Research Institute
state: Arizona
city: Fullerton
country: United States
facility: Neurology Center of North Orange County
state: California
city: La Jolla
country: United States
facility: University of California, San Diego
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Pasadena
country: United States
facility: SC3 Research Group - Pasadena
state: California
city: Hamden
country: United States
facility: Geriatric and Adult Psychiatry
state: Connecticut
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Stamford
country: United States
facility: Ki Health PARTNERS LLC DBA NEW ENGLAND INSTITUTE FOR CLINICAL RESEARCH
state: Connecticut
city: Delray Beach
country: United States
facility: Brain Matters Research
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Tampa
country: United States
facility: USF Health Byrd Alzheimer's Institute
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Great Lakes Clinical Trials
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Baton Rouge
country: United States
facility: Pennington Biomedical Research Center
state: Louisiana
city: Bangor
country: United States
facility: Northern Light Acadia Hospital
state: Maine
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan, Ann Arbor
state: Michigan
city: East Lansing
country: United States
facility: Michigan State University
state: Michigan
city: Chesterfield
country: United States
facility: Galen Research
state: Missouri
city: Las Vegas
country: United States
facility: Cleveland Clinic Lou Ruvo Center
state: Nevada
city: Princeton
country: United States
facility: Princeton Medical Institute
state: New Jersey
city: Bronx
country: United States
facility: James J. Peters VAMC
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University Department of Geriatrics
state: New York
city: Beachwood
country: United States
facility: Case Western Reserve University
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Tulsa
country: United States
facility: Tulsa Clinical Research
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Norristown
country: United States
facility: Keystone Clinical Studies, LLC
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Wilkes-Barre
country: United States
facility: Geisinger Medical Clinic
state: Pennsylvania
city: Willow Grove
country: United States
facility: Abington Neurological Associates
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Charleston
country: United States
facility: CBRI, Roper Hospital
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt Memory & Alzheimer's Center
state: Tennessee
city: San Antonio
country: United States
facility: The Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases,University of Texas Health Science Center at San Antonio
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
References: