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

Focal Epilepsy Clinical Trial

— RISE 2  

Official title:

A Phase 2/3 Multicenter, Randomized, 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: NCT06132893
• Other study ID #: BHV7000-302
• Secondary ID: 2023-508539-30
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: March 14, 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

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 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:

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

Locations

Country	Name	City	State
United States	Accellacare	Ames	Iowa
United States	Dent Neurosciences Research Center	Amherst	New York
United States	Augusta University	Augusta	Georgia
United States	University of Colorado Anschultz Medical Campus	Aurora	Colorado
United States	MAESC	Bethesda	Maryland
United States	EZR Research LLC	Boca Raton	Florida
United States	Consultants in Epilepsy & Neurology, PLLC	Boise	Idaho
United States	Nova Clinical Research, LLC	Bradenton	Florida
United States	UVM MC	Burlington	Vermont
United States	NeuroScience Research Center	Canton	Ohio
United States	OnSite Clinical Solutions	Charlotte	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	Northwestern University	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	OSU	Columbus	Ohio
United States	OSU	Columbus	Ohio
United States	Clinical Research Solutions LLC	Cypress	Texas
United States	Neurology Consultants of Dallas, PA	Dallas	Texas
United States	Revive Research Institute, Inc.	Elgin	Illinois
United States	NEREG	Hackensack	New Jersey
United States	BCHP	Hawthorne	New York
United States	Hawaii Pacific Neuroscience	Honolulu	Hawaii
United States	Michael E. DeBakey VA Medical Center	Houston	Texas
United States	University of Florida (Jacksonville)	Jacksonville	Florida
United States	University of California San Diego	La Jolla	California
United States	Bluegrass Epilepsy Research	Lexington	Kentucky
United States	Clinical Trials, Inc.	Little Rock	Arkansas
United States	Inst of Neurology	Livingston	New Jersey
United States	University of California, Los Angeles	Los Angeles	California
United States	Floridian Research Institute	Miami	Florida
United States	University of Miami	Miami	Florida
United States	Accellacare	Mooresville	North Carolina
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Icahn School of Medicine at Mt. Sinai	New York	New York
United States	Northwell Health	New York	New York
United States	AdventHealth Orlando	Orlando	Florida
United States	AdventHealth Orlando	Orlando	Florida
United States	Profound Research LLC	Pasadena	California
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Barrow Neurological Institute	Phoenix	Arizona
United States	Medsol Clinical Research Center	Port Charlotte	Florida
United States	Henrico Doctors Neurology Associates, LLC	Richmond	Virginia
United States	Carilion Clinic	Roanoke	Virginia
United States	Revive Research Institute, Inc.	Rochester Hills	Michigan
United States	WRN	Rogers	Arkansas
United States	Minnesota Epilepsy Group, P.A.	Roseville	Minnesota
United States	Road Runner Research, Ltd	San Antonio	Texas
United States	UT Health San Antonio	San Antonio	Texas
United States	Javara	Silver Spring	Maryland
United States	Stony Brook Medicine	Stony Brook	New York
United States	Santos Research Center	Tampa	Florida
United States	Center for Neurosciences	Tucson	Arizona
United States	Encore Medical Research of Weston LLC.	Weston	Florida
United States	Pediatrix Medical Group of Florida	Winter Park	Florida
United States	Five Towns Neuroscience Research	Woodmere	New York

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 12-week double-blind treatment phase.	Baseline, Week 8 to Week 20
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 12 week double-blind phase to the observation phase.	Baseline, Week 8 to Week 20
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 20
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 DB phase). This objective will be measured by proportion of subjects that are seizure free during the double-blind phase.	Week 8 to Week 20
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 seizure 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 20 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 20
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 20
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 20