T2 Protect AD

CompletedPhase 2Results posted

Study of BHV-4157 in Alzheimer's Disease

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

Lead sponsor

Biohaven Pharmaceuticals, Inc.

Asset

troriluzole

Listed sites

Recruiting sites

Enrollment

350

actual

Study population

Alzheimer’s disease

Key I/E criteria

•Alzheimer's disease•MMSE 14-24•Study partner/caregiver required

Primary endpoints

•ADAS-Cog•Clinical Dementia Rating-Sum of Boxes (CDR-SB)

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Org study IDBHV4157-203

NCT IDNCT03605667

Timeline

Milestones

Study first posted2018-07-30actual

Study start2018-07-31actual

Primary completion2020-12-15actual

Study completion2021-12-23actual

Last update posted2023-12-06actual

Results first posted2023-12-06actual

Assets

Drug assets

troriluzole

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age50 Years

Maximum age85 Years

SexAll

Healthy volunteersNot accepted

Inclusion 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

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.

Endpoints (17)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Global cognition

Function / daily living

Behavior / neuropsychiatric

Neuroimaging

Safety / tolerability / PK

Global cognition

9 endpoints

Primary/protocol endpoint

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

ADAS-Cog

change from baseline, improvement

Primary/protocol endpoint

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

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Primary/registry result

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

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), units on a scale	Reported bounds
Troriluzolen=119 Participants	6.7	-5.3 - 8.1
Placebon=127 Participants	6.7	-5.4 - 8.1

Least square mean difference0.095% CI-1.8 - 1.8p0.9809Mixed model with repeated measures

Primary/registry result

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

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), units on a scale	Reported bounds
Troriluzolen=118 Participants	2.1	-1.7 - 2.5
Placebon=127 Participants	1.9	-1.5 - 2.3

Least square mean difference-0.295% CI-0.8 - 0.3p0.4474Mixed model with repeated measures

Secondary/protocol endpoint

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

Time frame:Baseline (Day 1) and Week 48

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Secondary/registry result

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

Time frame:Baseline (Day 1) and Week 48

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), units on a scale	Reported bounds
Troriluzolen=121 Participants	-3.6	--4.4 - -2.9
Placebon=128 Participants	-3.2	--4.0 - -2.5

Least square mean difference0.495% CI-0.6 - 1.3p0.4191Mixed model with repeated measures

Other/protocol endpoint

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

Time frame:Baseline (Day 1) and Week 48

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Other_pre_specified/registry result

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

Time frame:Baseline (Day 1) and Week 48

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), percent deformation	Reported bounds
Troriluzolen=48 Participants	-1.1	--1.6 - -0.6
Placebon=49 Participants	-1.6	--2.1 - -1.0

Least square mean difference-0.595% CI-1.2 - 0.3p0.2240ANCOVA

Model based summary statistics are from an ANCOVA with baseline MMSE total score as covariate.

Post_hoc/registry result

Number of Responders in Participants With ADAS-cog Total Change and MRI Hippocampal Volume Change at Week 48 in Mild APOE e4 Carrier Subgroup

Time frame:Baseline (Day 1) and Week 48

ADAS-Cog

threshold achievement, improvement

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Troriluzolen=45 Participants	14	-
Placebon=44 Participants	4	-

p0.0161Fisher Exact

Function / daily living

2 endpoints

Secondary/protocol endpoint

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

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Secondary/registry result

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

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), units on a scale	Reported bounds
Troriluzolen=119 Participants	-8.9	--10.8 - -7.1
Placebon=125 Participants	-7.4	--9.2 - -5.6

Least square mean difference1.695% CI-0.8 - 3.9p0.1950Mixed model with repeated measures

Behavior / neuropsychiatric

2 endpoints

Secondary/protocol endpoint

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

Time frame:Baseline (Day 1) and Week 48

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/registry result

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

Time frame:Baseline (Day 1) and Week 48

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), units on a scale	Reported bounds
Troriluzolen=120 Participants	2.3	-0.2 - 4.4
Placebon=125 Participants	3.8	-1.8 - 5.8

Least square mean difference1.595% CI-1.1 - 4.1p0.2583Mixed model with repeated measures

Neuroimaging

2 endpoints

Secondary/protocol endpoint

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

Time frame:Baseline (Day 1) and Week 48

change from baseline, improvement

Secondary/registry result

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

Time frame:Baseline (Day 1) and Week 48

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), percent deformation	Reported bounds
Troriluzolen=87 Participants	-1.1	--1.4 - -0.7
Placebon=90 Participants	-1.1	--1.5 - -0.8

Least square mean difference0.095% CI-0.6 - 0.5p0.8670ANCOVA

Model based summary statistics were from an analysis of covariance (ANCOVA) with baseline MMSE total score as covariate.

Safety / tolerability / PK

2 endpoints

Secondary/protocol endpoint

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.

event count, event

Secondary/registry result

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.

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Troriluzole - Randomization PhaseAny TEAEsn=178 Participants	146	-
Any serious TEAEsn=178 Participants	24	-
Any fatal AEn=178 Participants	2	-
Any serious TEAEs considered relatedn=178 Participants	3	-
Drug withdrawn due to an TEAEn=178 Participants	16	-
Placebo - Randomization PhaseAny TEAEsn=171 Participants	116	-
Any serious TEAEsn=171 Participants	14	-
Any fatal AEn=171 Participants	2	-
Any serious TEAEs considered relatedn=171 Participants	1	-
Drug withdrawn due to an TEAEn=171 Participants	3	-
Troriluzole - Randomization Phase/ Troriluzole - OLE PhaseAny TEAEsn=90 Participants	57	-
Any serious TEAEsn=90 Participants	9	-
Any fatal AEn=90 Participants	0	-
Any serious TEAEs considered relatedn=90 Participants	0	-
Drug withdrawn due to an TEAEn=90 Participants	5	-
Placebo - Randomization Phase/ Troriluzole - OLE PhaseAny TEAEsn=103 Participants	66	-
Any serious TEAEsn=103 Participants	16	-
Any fatal AEn=103 Participants	2	-
Any serious TEAEs considered relatedn=103 Participants	3	-
Drug withdrawn due to an TEAEn=103 Participants	12	-

Publications (1)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

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.
PMID40317057via DERIVED

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.