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

10 Oct 2024 → ongoing

Decision date (initial)

2024-07-31

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

N/A

External identifiers

EU CT number

2023-508539-30-00

ClinicalTrials.gov

NCT06132893

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Others, Efficacy

Part A:
To assess the safety and tolerability of BHV-7000 25 mg and 50 mg in subjects with refractory focal onset epilepsy.

Part B:
'To compare the efficacy of BHV-7000 75mg 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 1

1. Part A: There are no secondary objectives under Part A. Part B: To compare the efficacy of BHV-7000 75mg to placebo as an adjunctive therapy for refractory focal onset epilepsy as measured by the change from the Observation Phase in 28-day average seizure frequency.

Conditions and MedDRA coding

Refractory Focal Onset Epilepsy

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

No

IPD plan description

N/A

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Signed Written Informed Consent 2. Subject and/or caregiver must be able to read and understand eDiary in an available language. 3. Subjects must be able to swallow the BHV-7000 IP tablet(s) whole. 4. Male and Female subjects 18 to 75 years of age at time of consent 5. Ability to keep accurate seizure diaries and miss no more than 4 entries (daily seizure diary) out of 28 days demonstrating 85% or greater compliance with eDiary during OP. 6. 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. 7. Focal seizures (1) Focal aware seizures with clinically observable signs and/or symptoms (2) Focal impaired awareness seizures (3) Focal to bilateral tonic-clonic seizures 8. Drug Resistant Focal Onset Seizures (1) Subject meets the 2009 ILAE definition of drug resistant epilepsy, failure of adequate trials of two tolerated and appropriately chosen and used ASM schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom. 9. Current treatment with at least 1 and up to 3 ASMs and 4 epilepsy treatments in total.

Exclusion criteria 1

1. 1. Non-focal seizures defined by ILAE criteria (1) EEG shows any pattern not consistent with focal etiology of seizures (e.g., generalized spike-wave). (2) 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. (3) Subjects with confirmed generalized onset seizures. 2. 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. 3. Resection neurosurgery for seizures < 4 months prior to the screening visit. 4. Radiosurgery performed < 2 years prior to the screening visit. 5. 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. Part A: 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. Part B: 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 3

1. Part A: N/A Part B: - Change in log-transformed 28-day adjusted seizure frequency from OP over the 12-week DBP. -Change in log-transformed 28-day adjusted seizure frequency from OP over the first month of the DBP.
2. Part B: - 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. -Proportion of subjects that are seizure free during the DBP. -Change in log-transformed 7-day adjusted seizure frequency from OP over the first week of the DBP.
3. Part B: - Proportion of subjects at week 12 with PGI-C response of "minimally improved", "much improved", or "very much improved". -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 1

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

9 EU/EEA countries · 47 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 134 files

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

Application history

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