A Study to Determine if BHV-7000 is Effective and Safe in Adults With Refractory Focal Onset Epilepsy (RISE 2)

September 28, 2026 updated by: Biohaven Therapeutics Ltd.

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

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

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

This study has two parts, Part A and Part B. Part A is randomized 1:1:1 25 mg of BHV-7000, 50 mg of BHV-7000 or matching placebo. Part B is randomized 1:1 75mg BHV-7000 or matching placebo. Part B will start after Part A.

Study Type

Interventional

Enrollment (Estimated)

390

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina, C1181ACH
        • Hospital Italiano de Buenos Aires
      • Buenos Aires, Argentina, C1428AQK
        • Fundación Para La Lucha Contra Las Enfermedades Neurológicas de La Infancia - FLENI
      • Buenos Aires, Argentina, C1039AAO
        • Sanatorio de la Trinidad - Mitre
      • Córdoba, Argentina, X5004AOA
        • Instituto Privado Kremer
      • Córdoba, Argentina, X5008HHW
        • Conci Carpinella - Santa Rosa N° 748
    • Buenos Aires
      • Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, C1013AAB
        • STAT Research S.A.
    • Ciudad Autónoma de BuenosAires
      • Balvanera, Ciudad Autónoma de BuenosAires, Argentina, C1221ADC
        • Hospital General de Agudos Dr. José María Ramos Mejia
      • Buenos Aires, Ciudad Autónoma de BuenosAires, Argentina, C1437JCH
        • Hospital Británico de Buenos Aires
    • Tucumán Province
      • San Miguel de Tucumán, Tucumán Province, Argentina, T4000AXL
        • Investigaciones Sanatorio Del Sur
  • Austria
      • Salzburg, Austria, 5020
        • Christian Doppler-Klinik - Universitätsklinikum der PMU
      • Sankt Pölten, Austria, 3100
        • Universitätsklinikum St. Pölten
      • Vienna, Austria, 1090
        • Medizinische Universitat Wien (Medical University of Vienna)
    • Upper Austria
      • Linz, Upper Austria, Austria, 4020
        • Kepler Universitätsklinikum Linz - Med Campus III
  • Belgium
    • Antwerpen
      • Edegem, Antwerpen, Belgium, 2650
        • UZ Antwerpen
    • Brussels Capital
      • Anderlecht, Brussels Capital, Belgium, 1070
        • Hôpital Erasme
      • Brussels, Brussels Capital, Belgium, 1200
        • Cliniques Universitaires Saint-Luc
    • Namur
      • Yvoir, Namur, Belgium, 5530
        • CHU UCL Namur - Site Godinne
    • Oost-Vlaanderen
      • Ghent, Oost-Vlaanderen, Belgium, 9000
        • UZ Gent
  • Chile
    • Araucania
      • Temuco, Araucania, Chile, 4780000
        • Centro de especialidades médicas Vanguardia
    • Región-MetropolitanadeSantiago
      • Santiago, Región-MetropolitanadeSantiago, Chile, 8260094
        • Hospital Padre Hurtado
      • Santiago, Región-MetropolitanadeSantiago, Chile, 8320000
        • BIOCINETIC Ltda
      • Santiago, Región-MetropolitanadeSantiago, Chile, 8320000
        • Centro de Investigacion Clinica UC
    • Valparaiso
      • Viña del Mar, Valparaiso, Chile, 2520021
        • Instituto Neurologico Thalamus
  • Czechia
    • South Moravian
      • Brno, South Moravian, Czechia, 602 00
        • Fakultni nemocnice u sv. Anny v Brne
  • France
      • Rennes, France, 35033
        • Hôpital Pontchaillou
    • Bas-Rhin
      • Strasbourg, Bas-Rhin, France, 67000
        • CHU de Strasbourg - Hôpital de Hautepierre
    • Côte-d'Or
      • Dijon, Côte-d'Or, France, 21000
        • CHU Dijon Bourgogne
    • Haute-Garonne
      • Toulouse, Haute-Garonne, France, 31059
        • CHU de Toulouse-Hôpital Pierre-Paul Riquet-Site de Purpan
    • Hérault
      • Montpellier, Hérault, France, 34295
        • CHU de Montpellier- Hôpital Gui De Chauliac
    • Indre-et-Loire
      • Tours, Indre-et-Loire, France, 37000
        • CHRU de Tours - Hôpital Bretonneau
    • Meurthe-et-Moselle
      • Nancy, Meurthe-et-Moselle, France, 54000
        • CHRU Nancy
    • Nord
      • Lille, Nord, France, 59037
        • CHU de Lille - Hopital Claude Huriez
    • Rhône
      • Lyon, Rhône, France, 69003
        • Hospices Civils de Lyon - 59 Bd Pinel
  • Hungary
      • Budapest, Hungary, 1145
        • SE INK Juhasz Pal Epilepszia Központ
      • Budapest, Hungary, 1106
        • Budapesti Bajcsy-Zsilinszky Korhaz es Rendelointezet
    • Baranya
      • Pécs, Baranya, Hungary, 7623
        • Pécsi Tudományegyetem Klinikai Kozpont -Ret u.
    • Hajdú-Bihar
      • Debrecen, Hajdú-Bihar, Hungary, 4031
        • Debreceni Egyetem Klinikai Kozpont Kenezy Gyula Campus
  • Netherlands
    • North Brabant
      • Heeze, North Brabant, Netherlands, 5591 VE
        • Kempenhaeghe - PPDS
    • North Holland
      • Heemstede, North Holland, Netherlands, 2103 SW
        • Stichting Epilepsie Instellingen Nederland - Heemstede
    • Overijssel
      • Zwolle, Overijssel, Netherlands, 8025 BV
        • Stichting Epilepsie Instellingen Nederland - Dokter Denekampweg 20
  • Poland
      • Gdansk, Poland, 80-803
        • Copernicus Podmiot Leczniczy Sp. z o.o. - ul. Nowe Ogrody 1-6
      • Katowice, Poland, 40-594
        • Novo-Med Zielinski i wsp. Sp.J. - ul. Brynowska 44
      • Krakow, Poland, 31-156
        • LANDA Specjalistyczne Gabinety Lekarskie
      • Krakow, Poland, 30-727
        • Pratia MCM Kraków
    • Greater Poland Voivodeship
      • Poznan, Greater Poland Voivodeship, Poland, 60-702
        • AES - DRS - Synexus Polska Sp. z o.o. Oddzial w Poznaniu
    • Lublin Voivodeship
      • Lublin, Lublin Voivodeship, Poland, 20-078
        • Clinical Best Solutions - Lublin
      • Świdnik, Lublin Voivodeship, Poland, 21-040
        • NZOZ IGNIS dr med. Alicja Lobinska
    • Lubusz Voivodeship
      • Nowa Sól, Lubusz Voivodeship, Poland, 67-100
        • Twoja Przychodnia Nowosolskie Centrum Medyczne sp. z o.o
    • Lódzkie
      • Lodz, Lódzkie, Poland, 90-302
        • Santa Familia PTG Lodz
    • Masovian Voivodeship
      • Warsaw, Masovian Voivodeship, Poland, 02-172
        • MTZ Clinical Research Powered by PRATIA - PPDS
      • Warsaw, Masovian Voivodeship, Poland, 02-829
        • Neurosphera SP. Z O.O
      • Warsaw, Masovian Voivodeship, Poland, 02-957
        • Instytut Psychiatrii i Neurologii
    • Pomeranian Voivodeship
      • Gdansk, Pomeranian Voivodeship, Poland, 80-546
        • Centrum Badan Klinicznych PI-House sp. z o.o.
  • Slovenia
      • Maribor, Slovenia, 2000
        • University Clinical Centre Maribor
  • Switzerland
    • Zürich (de)
      • Zurich, Zürich (de), Switzerland, 8008
        • Klinik Lengg AG
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85013
        • Barrow Neurological Institute
      • Tucson, Arizona, United States, 85718
        • Center for Neurosciences
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • Clinical Trials, Inc.
    • California
      • La Jolla, California, United States, 92041
        • University of California San Diego
      • Los Angeles, California, United States, 90095
        • University of California, Los Angeles
      • Palo Alto, California, United States, 94304
        • Stanford Health Care
      • Pasadena, California, United States, 91105
        • Profound Research LLC
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Anschultz Medical Campus
    • Connecticut
      • New Haven, Connecticut, United States, 06519
        • Yale School of Medicine - Yale-New Haven Hospital
    • Florida
      • Boca Raton, Florida, United States, 33486
        • EZR Research LLC
      • Bradenton, Florida, United States, 34209
        • Nova Clinical Research, LLC
      • Jacksonville, Florida, United States, 32209
        • University of Florida (Jacksonville)
      • Miami, Florida, United States, 33136
        • University of Miami
      • Port Charlotte, Florida, United States, 33952
        • Medsol Clinical Research Center
      • Tampa, Florida, United States, 33615
        • Santos Research Center
      • Weston, Florida, United States, 33331
        • Encore Medical Research of Weston LLC.
    • Georgia
      • Augusta, Georgia, United States, 30912
        • Augusta University
    • Hawaii
      • Honolulu, Hawaii, United States, 96817
        • Hawaii Pacific Neuroscience
    • Idaho
      • Boise, Idaho, United States, 83702
        • Consultants in Epilepsy & Neurology, PLLC
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University
      • Elgin, Illinois, United States, 60123
        • Revive Research Institute, Inc.
    • Kentucky
      • Lexington, Kentucky, United States, 40504
        • Bluegrass Epilepsy Research
    • Maryland
      • Bethesda, Maryland, United States, 20817
        • MAESC
      • Silver Spring, Maryland, United States, 20901
        • Javara
    • Minnesota
      • Roseville, Minnesota, United States, 55113
        • Minnesota Epilepsy Group, P.A.
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • NEREG
      • Livingston, New Jersey, United States, 07039
        • Inst of Neurology
    • New York
      • Amherst, New York, United States, 14226
        • Dent Neurosciences Research Center
      • Hawthorne, New York, United States, 10532
        • BCHP
      • New York, New York, United States, 10021
        • Northwell Health
      • Stony Brook, New York, United States, 11794
        • Stony Brook Medicine
      • Woodmere, New York, United States, 11598
        • Five Towns Neuroscience Research
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest Baptist
    • Ohio
      • Canton, Ohio, United States, 44718
        • NeuroScience Research Center
      • Cincinnati, Ohio, United States, 45267
        • University of Cincinnati
      • Columbus, Ohio, United States, 43214
        • OSU
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University
      • Pittsburgh, Pennsylvania, United States, 15213
        • UPMC
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center
    • Texas
      • Dallas, Texas, United States, 75243
        • Neurology Consultants of Dallas, PA
      • Fort Worth, Texas, United States, 76104
        • Tarrant Neurology Consultants
      • San Antonio, Texas, United States, 78229
        • UT Health San Antonio
      • San Antonio, Texas, United States, 78249
        • Road Runner Research, Ltd
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • University of Utah
    • Virginia
      • Charlottesville, Virginia, United States, 22903
        • University of Virginia
      • Richmond, Virginia, United States, 23235
        • Henrico Doctors Neurology Associates, LLC
      • Roanoke, Virginia, United States, 24011
        • Carilion Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 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

Key Exclusion Criteria:

  1. History of status epilepticus (convulsive status epilepticus for > 5 minutes or focal status epilepticus with impaired consciousness 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: BHV-7000 25 mg Part A
Drug: BHV-7000

BHV-7000 25 mg. Participants will take blinded investigational product (IP) once daily

Drug: BHV-7000

BHV-7000 50 mg. Participants will take blinded investigational product (IP) once daily

Drug: BHV-7000

BHV-7000 75 mg. Participants willtake blinded investigational product(IP) once daily
Experimental: BHV-7000 50 mg Part A
Drug: BHV-7000

BHV-7000 25 mg. Participants will take blinded investigational product (IP) once daily

Drug: BHV-7000

BHV-7000 50 mg. Participants will take blinded investigational product (IP) once daily

Drug: BHV-7000

BHV-7000 75 mg. Participants willtake blinded investigational product(IP) once daily
Placebo Comparator: Placebo Part A
Drug: Placebo

Matching placebo taken once daily
Experimental: BHV-7000 75 mg Part B
Drug: BHV-7000

BHV-7000 25 mg. Participants will take blinded investigational product (IP) once daily

Drug: BHV-7000

BHV-7000 50 mg. Participants will take blinded investigational product (IP) once daily

Drug: BHV-7000

BHV-7000 75 mg. Participants willtake blinded investigational product(IP) once daily
Placebo Comparator: Placebo Part B
Drug: Placebo

Matching placebo taken once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part B: Change from Baseline in 28-day average seizure frequency
Time Frame: Baseline, Week 8 to Week 20 of Part B

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 OP (observational phase) 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 of Part B
Part A: Number of Participants With Deaths, Serious AEs (SAEs), AEs Leading to Study Drug Discontinuation, and moderate or severe AEs
Time Frame: Week 8 to Week 20 of Part A

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 of Part A
Part A: Number of Participants With Clinically Significant Laboratory Abnormalities
Time Frame: Week 8 to Week 20 of Part A

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 of Part A

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part B: Percentage of Participants with at at least 50% reduction in seizure frequency per month
Time Frame: Baseline, Week 8 to Week 20 of Part B

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 of Part B
Part B: Change from Baseline in 28-day average seizure frequency during first month of treatment
Time Frame: Baseline, Week 8 to Week 12 of Part B

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 of Part B
Part B: Percentage of Participants with at at least 75% reduction in seizure frequency per month
Time Frame: Baseline, Week 8 to Week 20 of Part B

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 of Part B
Part B: Percentage of Participants with seizure freedom during DB Phase
Time Frame: Week 8 to Week 20 of Part B

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 of Part B
Part B: Change from baseline in 7-day adjusted seizure frequency during first week of treatment
Time Frame: Baseline, Week 8 to Week 9 of Part B

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 of Part B
Part B: Change from baseline in Patient Global Impression of Change (PGI-C)
Time Frame: Baseline, Week 20 of Part B

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 12 of double-blind treatment phase 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 of Part B
Part B: Number of Participants With Deaths, Serious AEs (SAEs), AEs Leading to Study Drug Discontinuation, and moderate or severe AEs
Time Frame: Week 8 to Week 20 of Part B

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 of Part B
Part B: Number of Participants With Clinically Significant Laboratory Abnormalities
Time Frame: Week 8 to Week 20 of Part B

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 of Part B

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Biohaven Therapeutics Ltd.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 14, 2024

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

November 10, 2023

First Submitted That Met QC Criteria

November 10, 2023

First Posted (Actual)

November 15, 2023

Study Record Updates

Last Update Posted (Actual)

September 30, 2026

Last Update Submitted That Met QC Criteria

September 28, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BHV7000-302
  • 2023-508539-30 (Registry Identifier: EU CTR)
  • 2023 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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