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

Focal Epilepsy Clinical Trial

— RISE 3  

Official title:

A Phase 2/3 Multicenter, Randomization, Double-Blind, Placebo-Controlled, Study to Evaluate the Efficacy, Safety and Tolerability of BHV-7000 in Subjects With Refractory Focal Onset Epilepsy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06309966
• Other study ID #: BHV7000-303
• Secondary ID: 2023-808811-21
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: May 13, 2024
• Est. completion date: September 2025

Study information

• Verified date: June 2024
• Source: Biohaven Pharmaceuticals, Inc.
• Contact: Chief Medical Officer
• Phone: 203-404-0410
• Email: clinicaltrials[@]biohavenpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether BHV-7000 is effective in the treatment of refractory focal epilepsy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 390
• Est. completion date: September 2025
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Key Inclusion Criteria:

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.)

Key Exclusion Criteria:

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

Related Conditions & MeSH terms

• Epilepsies, Partial
• Epilepsy
• Focal Epilepsy

Intervention

Drug:
• BHV-7000
BHV-7000 50 mg. Participants will take blinded investigational product (IP) once daily
• BHV-7000
BHV-7000 75 mg. Participants will take blinded investigational product (IP) once daily
• Placebo
Matching placebo taken once daily

Locations

Country	Name	City	State
United States	DelRicht Research	Baton Rouge	Louisiana
United States	UNC-Chapel Hill	Chapel Hill	North Carolina
United States	MUSC	Charleston	South Carolina
United States	WR-ClinSearch	Chattanooga	Tennessee
United States	Cincinatti Children's Hospital	Cincinnati	Ohio
United States	ANESC Research	El Paso	Texas
United States	Northwell Health	Great Neck	New York
United States	UTHealth Houston	Houston	Texas
United States	Dm Healthworks	Kissimmee	Florida
United States	Memorialcare Miller Children's & Women's Hospital Long Beach	Long Beach	California
United States	Y&L Advance Health Care, Inc d/b/a Elite Clinical Research	Miami	Florida
United States	Intermountain Health	Murray	Utah
United States	DelRicht Research	New Orleans	Louisiana
United States	University Medical Center New Orleans	New Orleans	Louisiana
United States	Comprehensive Neurology Clinic	Orlando	Florida
United States	Research Institute of Orlando	Orlando	Florida
United States	ARENSIA Exploratory Medicine	Phoenix	Arizona
United States	Knight Neurology	Rockledge	Florida
United States	PENS	Tampa	Florida
United States	Medstar Health Research Institute	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Biohaven Therapeutics Ltd.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline in 28-day average seizure frequency	To compare the efficacy of each of 2 doses of BHV-7000 to placebo as an adjunctive therapy for refractory focal onset epilepsy as measured by the change from baseline in 28-day average seizure frequency. The primary objective will be measured by comparing the observation phase (8 weeks) to the 8-week double-blind treatment phase.	Baseline, Week 8 to Week 16
Secondary	Percentage of Participants with at at least 50% reduction in seizure frequency per month	To compare the efficacy 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). This objective will be measured by comparing the proportion of subjects with at least a 50% reduction in 28-day average seizure frequency over the course of the 8 week double-blind phase to the observation phase.	Baseline, Week 8 to Week 16
Secondary	Change from Baseline in 28-day average seizure frequency during first month of treatment	To compare the efficacy of BHV-7000 to placebo during the first month of treatment. This objective will be measured by the change in log-transformed 28-day adjusted seizure frequency from observation phase over the first month of the double blind phase.	Baseline, Week 8 to Week 12
Secondary	Percentage of Participants with at at least 75% reduction in seizure frequency per month	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). This objective will be measured by comparing the proportion of subjects with at least a 75% reduction in 28-day average seizure frequency over the course of the double-blind phase compared to the observation phase.	Baseline, Week 8 to Week 16
Secondary	Change from baseline in 7-day adjusted seizure frequency during first week of treatment	To compare the efficacy of BHV-7000 to placebo during the first week of treatment. This objective will be measured by the change in log-transformed 7-day adjusted seziure frequency from observation phase over the first week of the double-blind phase.	Baseline, Week 8 to Week 9
Secondary	Change from baseline in Patient Global Impression of Change (PGI-C)	To compare the efficacy of BHV-7000 to placebo on the patient global impression of change (PGI-C). This objective will be measured by proportion of subjects at week 16 with a PGI-C response of "minimally improved", "much improved" or "very much improved". This scale is a 7-point Likert scale with response options of: (1) "very much improved" , (2) "much improved", (3) "minimally improved", (4) "no change", (5) "minimally worse", (6) "much worse", (7) and "very much worse"	Baseline, Week 16
Secondary	Number of Participants With Deaths, Serious AEs (SAEs), AEs Leading to Study Drug Discontinuation, and moderate or severe AEs	To assess the safety and tolerability of BHV-7000. This objective will be measured by assessing the number of unique subjects with deaths, SAEs, AEs leading to discontinuation, and moderate and severe AEs.	Week 8 to Week 16
Secondary	Number of Participants With Clinically Significant Laboratory Abnormalities	To assess the safety and tolerability of BHV-7000. This objective will be measured by assessing the number of unique subjects with grade 3 and 4 laboratory abnormalities.	Week 8 to Week 16
Secondary	Percentage of Participants with seizure freedom during DB Phase	To compare the efficacy of BHV-7000 to placebo on seizure freedom (100% seizure reduction during the DBP phase). This objective will be measured by proportion of subjects that are seizure free during the double-blind phase.	Week 8 to Week 16