A Study to Determine if BHV-7000 is Effective and Safe in Adults With Refractory Focal Onset Epilepsy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Biohaven Therapeutics Ltd.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

25 Sep 2024 → ongoing

Decision date (initial)

2024-09-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Biohaven Therapeutics, Ltd. c/o Biohaven Pharmaceuticals, Inc. (BPI)

External identifiers

EU CT number

2023-508811-21-00

ClinicalTrials.gov

NCT06309966

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Efficacy, Pharmacokinetic

To compare the efficacy of each of 2 dose strengths of BHV-7000 to placebo as adjunctive therapy for refractory focal onset epilepsy as measured by the proportion of subjects that have at least a 50% reduction in seizures per month (28 days).

Secondary objectives 7

1. To compare the efficacy of each of 2 dose strengths of BHV-7000 to placebo as an adjunctive therapy for refractory focal onset epilepsy as measured by the change from the OP in 28-day average seizure frequency.
2. To compare the efficacy of BHV-7000 to placebo during the first month of treatment.
3. To compare the efficacy of BHV-7000 to placebo as measured by the proportion of subjects that have at least a 75% reduction in seizures per month (28 days).
4. To compare the efficacy of BHV-7000 to placebo on seizure freedom (100% seizure reduction during the DBP phase).
5. To compare the efficacy of BHV-7000 to placebo during the first week of treatment.
6. To compare the efficacy of BHV-7000 to placebo on the patient global impression of change (PGI-C) at week 8.
7. To assess the safety and tolerability of BHV-7000.

Conditions and MedDRA coding

Refractory Focal Onset Epilepsy

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Male and Female participants 18 to 75 years of age at time of consent.
2. Diagnosis of Focal Onset Epilepsy at least 1 year prior to screening visit defined by 2017 International League Against Epilepsy (ILAE) Classification and based on requirements of Epilepsy Adjudication criteria. a. Focal seizures i. Focal aware seizures with clinically observable signs and/or symptoms ii. Focal impaired awareness seizures with clinically observable signs and/or symptoms iii. Focal to bilateral tonic-clonic seizures
3. Subject meets the 2009 ILAE definition of drug resistant epilepsy, failure of adequate trials of two tolerated and appropriately chosen and used anti-seizure medication (ASM) schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom.
4. Ability to keep accurate seizure diaries
5. Current treatment with at least 1 and up to 3 ASMs and 4 epilepsy treatments in total (e.g., 3 ASMs + 1 diet regimen; 2 ASMs + 1 diet regimen + 1 device, etc.)

Exclusion criteria 6

1. History of status epilepticus (convulsive status epilepticus for > 5 minutes or focal status epilepticus with impaired conscious for > 10 minutes) within the last 6 months prior to screening visit that is not consistent with the subject's habitual seizure.
2. History of repetitive/cluster seizures (where individual seizures cannot be counted) within the last 6 months prior to screening visit and during observation phase.
3. Resection neurosurgery for seizures <4 months prior to the screening visit.
4. Radiosurgery performed <2 years prior to the screening visit.
5. Subjects with only focal aware nonmotor seizures which involve subjective sensory or psychic phenomena only, without impairment of consciousness or awareness (formally called simple partial seizures), with or without ictal EEG correlation with clinical symptoms.
6. Any condition that would interfere with the subject's ability to comply with study instructions, place the subject at unacceptable risk, and/or confound the interpretation of safety or efficacy data from the study, as judged by the Investigator

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of subjects with at least a 50% reduction in 28-day average seizure frequency over the course of the DBP compared to the OP.

Secondary endpoints 7

1. Change in log-transformed 28-day adjusted seizure frequency from OP over the 8-week DBP.
2. Change in log-transformed 28-day adjusted seizure frequency from OP over the first month of the DBP.
3. Proportion of subjects with at least a 75% reduction in 28-day average seizure frequency over the course of the DBP compared to the OP.
4. Proportion of subjects that are seizure free during the DBP.
5. Change in log-transformed 7-day adjusted seizure frequency from OP over the first week of the DBP.
6. Proportion of subjects at Week 8 with PGI-C response of “minimally improved”, “much improved” or “very much improved”.
7. Safety is assessed by the number of unique subjects with deaths, SAEs, AEs leading to discontinuation, moderate and severe AEs and grade 3 and 4 laboratory abnormalities.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Biohaven Therapeutics Ltd.

Sponsor organisation

Biohaven Therapeutics Ltd.

Address

215 Church Street

City

New Haven

Postcode

06510-1803

Country

United States

Scientific contact point

Organisation

Biohaven Therapeutics Ltd.

Contact name

Research and Development Medical Director

Public contact point

Organisation

Biohaven Therapeutics Ltd.

Contact name

Chief Operating Officer

Third parties 8

Locations

11 EU/EEA countries · 76 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 109 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

26 submissions — initial application plus substantial / non-substantial modifications