Clinical trial • Phase II/III • Neurology

BHV-7000 for Refractory focal onset epilepsy

Phase II/III trial of BHV-7000 for Refractory focal onset epilepsy.

Overview

Trial Therapeutic Area
Neurology
Trial Disease
Refractory focal onset epilepsy
Trial Stage
Phase II/III
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
05-04-2024
First CTIS Authorization Date
26-07-2024

Trial design

Randomised, matching placebo (matching placebo part a / part b). active arms: bhv-7000 25 mg (part a), bhv-7000 50 mg (part a), bhv-7000 75 mg (part b; bhv-7000 extended release 25 mg and 50 mg tablets).-controlled Phase II/III trial in Hungary, Austria, Belgium and others.

Randomised
Yes
Comparator
Matching placebo (matching placebo Part A / Part B). Active arms: BHV-7000 25 mg (Part A), BHV-7000 50 mg (Part A), BHV-7000 75 mg (Part B; BHV-7000 Extended Release 25 mg and 50 mg tablets).
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
356
Trial Duration For Participant
154

Eligibility

Recruits 356 Vulnerable population selected (isVulnerablePopulationSelected = true). Study requires Signed Written Informed Consent from adult subjects (18–75). Caregiver-specific informed consent materials are available (e.g. caregiver ICFs and optional caregiver consent documents listed in the dossier), and pre-ICF telephone consent/contacts (Scout Clinical Pre-ICF Telephone Data Consent) are used..

Vulnerable Population
Vulnerable population selected (isVulnerablePopulationSelected = true). Study requires Signed Written Informed Consent from adult subjects (18–75). Caregiver-specific informed consent materials are available (e.g. caregiver ICFs and optional caregiver consent documents listed in the dossier), and pre-ICF telephone consent/contacts (Scout Clinical Pre-ICF Telephone Data Consent) are used.

Inclusion criteria

  • {"criterion_text":"- 1. Signed Written Informed Consent\n- 2. Subject and/or caregiver must be able to read and understand eDiary in an available language.\n- 3. Subjects must be able to swallow the BHV-7000 IP tablet(s) whole.\n- 4. Male and Female subjects 18 to 75 years of age at time of consent\n- 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.\n- 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.\n- 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\n- 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.\n- 9. Current treatment with at least 1 and up to 3 ASMs and 4 epilepsy treatments in total."}

Exclusion criteria

  • {"criterion_text":"- 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.\n- 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.\n- 3. Resection neurosurgery for seizures < 4 months prior to the screening visit.\n- 4. Radiosurgery performed < 2 years prior to the screening visit.\n- 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 endpoints

  • {"endpoint_text":"- 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.","definition_or_measurement_approach":"Part A: Safety measured by count of unique subjects with deaths, serious adverse events (SAEs), adverse events (AEs) leading to discontinuation, moderate and severe AEs, and grade 3 and 4 laboratory abnormalities. Part B: Efficacy measured as the proportion of subjects achieving at least a 50% reduction in 28-day average seizure frequency during the Double-Blind Phase (DBP) compared to the Observation Phase (OP)."}

Secondary endpoints

  • {"endpoint_text":"- 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.","definition_or_measurement_approach":"Change from Observation Phase (OP) in log-transformed 28-day adjusted seizure frequency measured over the 12-week Double-Blind Phase (DBP) and over the first month of the DBP."}
  • {"endpoint_text":"- 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.","definition_or_measurement_approach":"Responder analyses: proportion with ≥75% reduction in 28-day average seizure frequency vs OP; proportion seizure-free during DBP; change in log-transformed 7-day adjusted seizure frequency from OP during first week of DBP."}
  • {"endpoint_text":"- 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.","definition_or_measurement_approach":"PGI-C (Patient Global Impression of Change) at Week 12 categorized as minimally/much/very much improved; safety assessment as per Part A metrics (counts of deaths, SAEs, AEs leading to discontinuation, moderate/severe AEs and grade 3/4 lab abnormalities)."}

Recruitment

Registry Or Advocacy Recruitment
True, Site-and-Patient-Advocacy-Contact-List-for-ICF (document) referenced; site advocacy contact lists provided.
Digital Remote Recruitment
True, digital methods include social media advertising (Rise social media ads), study website listings (Rise website), email communications and pre-ICF telephone contact (Scout Clinical pre-ICF) as documented.
Planned Sample Size
356
Recruitment Window Months
22
Consent Approach
Signed Written Informed Consent required from each subject (adults 18–75). Pre-ICF telephone consent/contact (Scout Clinical Pre-ICF Telephone Data Consent) is used. Caregiver-specific ICFs and optional caregiver consent materials are available. Main ICFs and related consent materials are provided in multiple languages (examples in dossier: Hungarian, Polish, French, German, Dutch, Croatian, Czech, Slovenian, English).

Methods

  • Poland: Rise social media ads (document: K2_BHV7000-302_Rise-Social-Media-Ads_PL_Polish_Public)
  • Poland: Rise website (document: K2_BHV7000-302_Rise-Website_PL_Polish_Public)
  • Trifold/print brochures (Rise Trifold) used in multiple countries (documents: Rise-Trifold files across countries)
  • Scout Clinical pre-ICF telephone contact/consent (documents: Scout Clinical Pre-ICF Telephone Data Consent files across countries)
  • Site-based recruitment and patient brochures (various country recruitment arrangement documents K1/K2 per country)
  • Site-and-Patient-Advocacy contact lists (document: L2_BHV7000-302_Site-and-Patient-Advocacy-Contact-List-for-ICF_AT_Public)
  • Email and study brochure communications (Scout Clinical Email/Study Brochure documents present for several countries)

Geography

Total Number Of Sites
47
Total Number Of Participants
194

Hungary

Earliest CTIS Part Ii Submission Date
02-07-2024
Latest Decision Or Authorization Date
30-01-2026
Processing Time Days
577
Number Of Sites
4
Number Of Participants
20

Sites

Site Name
University Of Pecs
Department Name
Neurológiai Klinika
Contact Person Name
József Janszky
Contact Person Email
janszky.jozsef@pte.hu
Site Name
University Of Debrecen
Department Name
DE Klinikai Központ (DEKK) Neurológiai Klinika
Contact Person Name
Palma Piros
Site Name
Orszagos Mentalis Ideggyogyaszati Es Idegsebeszeti Intezet
Department Name
Neurológia
Contact Person Name
Anna Kelemen
Contact Person Email
akelemen61@gmail.com
Site Name
Budapesti Bajcsy-Zsilinszky Korhaz Es Rendelointezet
Department Name
Neurológia Osztály
Contact Person Name
Balázs Czigler
Contact Person Email
bazsoczi@gmail.com

Austria

Earliest CTIS Part Ii Submission Date
28-06-2024
Latest Decision Or Authorization Date
31-01-2026
Processing Time Days
584
Number Of Sites
4
Number Of Participants
5

Sites

Site Name
Gemeinnutzige Salzburger Landes kliniken Betriebsgesellschaft mbH
Contact Person Name
Eugen Trinka
Contact Person Email
e.trinka@salk.at
Site Name
Noe LGA Gesundheit Region Mitte GmbH
Department Name
Klinische Abteilung für Neurologie
Contact Person Name
Stefan Oberndorfer
Site Name
Johannes Kepler University Linz
Department Name
Universitätsklinik für Neurologie
Contact Person Name
Rainer Dormann
Site Name
Medical University Of Vienna
Department Name
Universitätsklinik für Neurologie
Contact Person Name
Ekaterina Pataraia

Belgium

Earliest CTIS Part Ii Submission Date
28-06-2024
Latest Decision Or Authorization Date
29-01-2026
Processing Time Days
580
Number Of Sites
5
Number Of Participants
20

Sites

Site Name
Hopital Erasme
Department Name
Neurology
Contact Person Name
Benjamin Legros
Contact Person Email
blegros@ulb.ac.be
Site Name
Centre Hospitalier Universitaire Dinant Godinne Sainte-Elisabeth-UCL-Namur
Department Name
Neurology
Contact Person Name
Michel Ossemann
Contact Person Email
michel.ossemann@uclouvain.be
Site Name
Universitair Ziekenhuis Gent
Department Name
Neurology
Contact Person Name
Mathieu Sprengers
Contact Person Email
mathieu.sprengers@ugent.be
Site Name
Cliniques Universitaires Saint-Luc
Department Name
Neurology
Contact Person Name
Riem El Tahry
Contact Person Email
riem.eltahry@uclouvain.be
Site Name
Antwerp University Hospital
Department Name
Neurology
Contact Person Name
Sarah Weckhuysen
Contact Person Email
sarah.weckhuysen@uza.be

Netherlands

Earliest CTIS Part Ii Submission Date
19-07-2024
Latest Decision Or Authorization Date
28-01-2026
Processing Time Days
558
Number Of Sites
3
Number Of Participants
8

Sites

Site Name
Epilepsy Instellingen Nederland Stichting
Department Name
Neurology
Contact Person Name
Hinke van Thuijl
Contact Person Email
hvthuijl@sein.nl
Site Name
Epilepsy Instellingen Nederland Stichting
Department Name
Neurology
Contact Person Name
Claire Donjacour
Contact Person Email
cdonjacour@sein.nl
Site Name
Kempenhaeghe
Department Name
Neurology
Contact Person Name
Selmer Lauwers

Slovenia

Earliest CTIS Part Ii Submission Date
23-04-2024
Latest Decision Or Authorization Date
30-01-2026
Processing Time Days
647
Number Of Sites
1
Number Of Participants
8

Sites

Site Name
UNIVERZITETNI KLINICNI CENTER MARIBOR
Department Name
Neurology Clinic
Contact Person Name
Karmen Vizjak Šterman
Contact Person Email
karmen.vizjak@gmail.com

Croatia

Earliest CTIS Part Ii Submission Date
28-06-2024
Latest Decision Or Authorization Date
30-01-2026
Processing Time Days
581
Number Of Sites
5
Number Of Participants
20

Sites

Site Name
Klinički bolnički centar Rijeka (Clinical Hospital Center Rijeka)
Department Name
Neurology and Child Psychiatry
Contact Person Name
Igor Prpić
Contact Person Email
Igor.prpic@medri.uniri.hr
Site Name
Klinička bolnica Sveti Duh (Clinical Hospital „Sveti Duh“)
Department Name
Neurology
Contact Person Name
Sanja Tomasović
Contact Person Email
stomasovic98@gmail.com
Site Name
Klinički bolnički centar Zagreb (University Hospital Center Zagreb)
Department Name
Neurology
Contact Person Name
Željka Petelin Gadže
Contact Person Email
zeljka.petelin@mef.hr
Site Name
Klinička bolnica Dubrava (University Hospital Dubrava)
Department Name
Neurology
Contact Person Name
Silvio Bašić
Contact Person Email
sbasic@kbd.hr
Site Name
Sestre Milosrdnice University Hospital Center (Klinički bolnički centar Sestre Milosrdnice)
Department Name
Paediatric clinic
Contact Person Name
Maša Malenica
Contact Person Email
malenicamasa96@gmail.com

Czechia

Earliest CTIS Part Ii Submission Date
01-07-2024
Latest Decision Or Authorization Date
29-01-2026
Processing Time Days
577
Number Of Sites
2
Number Of Participants
18

Sites

Site Name
Fakultni Nemocnice V Motole
Department Name
Neurologická klinika 2.LF UK a FN
Contact Person Name
Petr Marusič
Contact Person Email
petr.marusic@fnmotol.cz
Site Name
Fakultni Nemocnice U Sv Anny V Brne
Department Name
I. neurologická klinika
Contact Person Name
Milan Brázdil
Contact Person Email
milan.brazdil@fnusa.cz

Poland

Earliest CTIS Part Ii Submission Date
28-06-2024
Latest Decision Or Authorization Date
30-01-2026
Processing Time Days
581
Number Of Sites
14
Number Of Participants
71

Sites

Site Name
Synexus Polska Sp. z o.o.
Contact Person Name
Dorota Strzelecka
Contact Person Email
dorota.strzelecka@synexus.com
Site Name
NZOZ IGNIS dr med. Alicja Łobinska
Contact Person Name
Alicja Łobińska
Contact Person Email
alalob@tlen.pl
Site Name
Centrum Badan Klinicznych Pi-House Sp. z o.o.
Contact Person Name
Magdalena Nowowiejska-Jastrzebowska
Contact Person Email
m.nowojast@pihouse.pl
Site Name
Pratia S.A.
Contact Person Name
Elżbieta Szczygieł-Pilut
Contact Person Email
eszczygiel-pilut@pratia.pl
Site Name
Instytut Psychiatrii I Neurologii
Department Name
II Klinika Neurologiczna
Contact Person Name
Iwona Kurkowska-Jastrzębska
Contact Person Email
ikurkowska@ipin.edu.pl
Site Name
Vistamed & Vertigo Sp. z o.o.
Contact Person Name
Justyna Chojdak-Lukasiewicz
Contact Person Email
j.cholewa@vistamed.pl
Site Name
Mtz Clinical Research Powered By Pratia
Contact Person Name
Zygmunt Jamrozik
Contact Person Email
zjamrozik@pratia.pl
Site Name
Neurosphera Sp. z o.o.
Contact Person Name
Beata Zwolińska
Contact Person Email
beata.m.zwolinska@gmail.com
Site Name
Novo-Med Zielinski I Wspolnicy Sp. j.
Department Name
NIEPUBLICZNY ZAKŁAD OPIEKI ZDROWOTNEJ NOVO-MED
Contact Person Name
Tomasz Zieliński
Contact Person Email
tzielinski@op.pl
Site Name
Twoja Przychodnia Nowosolskie Centrum Medyczne Sp. z o.o.
Contact Person Name
Agata Kłósek
Contact Person Email
klosek@twojaprzychodnia.com
Site Name
Copernicus Podmiot Leczniczy Sp. z o.o.
Department Name
Oddział Neurologiczny
Contact Person Name
Waldemar Fryze
Contact Person Email
w.fryze@wp.pl
Site Name
Clinical Best Solutions Sp. z o.o. S.K.
Contact Person Name
Jacek Gawłowicz
Contact Person Email
gawlowiczj@wp.pl
Site Name
LANDA Specjalistyczne Gabinety Lekarskie
Contact Person Name
Magdalena Bosak
Contact Person Email
bosak@smo.com.pl
Site Name
Santa Sp. z o.o.
Contact Person Name
Maria Fortak-Michalska
Contact Person Email
mfortak@op.pl

France

Earliest CTIS Part Ii Submission Date
04-07-2024
Latest Decision Or Authorization Date
20-03-2026
Processing Time Days
624
Number Of Sites
9
Number Of Participants
24

Sites

Site Name
Centre Hospitalier Regional Universitaire De Tours
Department Name
Service de Neurologie et de Neurophysiologie Clinique
Contact Person Name
Julien Biberon
Contact Person Email
j.biberon@chu-tours.fr
Site Name
Centre Hospitalier Universitaire De Dijon
Department Name
Département de Neurophysiologie Clinique et Centre SLA
Contact Person Name
Martine Lemesle-Martin
Contact Person Email
martine.lemesle@chu-dijon.fr
Site Name
Centre Hospitalier Universitaire De Toulouse
Department Name
Département d’Explorations Neurophysiologiques
Contact Person Name
Luc Valton
Contact Person Email
Valton.l@chu-toulouse.fr
Site Name
CHRU De Nancy
Department Name
Service de Neurologie
Contact Person Name
Louis Maillard
Contact Person Email
l.maillard@chu-nancy.fr
Site Name
Hospices Civils De Lyon
Department Name
Département de Neurologie fonctionnelle et d’Epileptologie
Contact Person Name
Sylvain Rheims
Contact Person Email
sylvain.rheims@chu-lyon.fr
Site Name
Centre Hospitalier Universitaire De Lille
Department Name
Département de Neurophysiologies Clinique
Contact Person Name
Philippe Derambure
Site Name
Centre Hospitalier Universitaire De Rennes
Department Name
Service de Neurologie – Service d’Epileptologie Vincent VAN GOGH
Contact Person Name
Anca Nica
Contact Person Email
anca.nica@chu-rennes.fr
Site Name
Centre Hospitalier Universitaire De Montpellier
Department Name
Département Neurologie Exploratoire et Epileptologie
Contact Person Name
Arielle Crespel
Contact Person Email
a-crespel@chu-montpellier.fr
Site Name
Les Hopitaux Universitaires De Strasbourg
Department Name
Département de neurologie
Contact Person Name
Maria Paola Valenti Hirsch

Sponsor

Primary sponsor

Full Name
Biohaven Therapeutics Ltd.
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
Syneos Health Clinique Inc.
Responsibilities
PK analysis
Name
PPD Development L.P.
Responsibilities
codes:1,10,11,12,13,14,2,5,6,8,9
Name
PPD Global Central Labs
Responsibilities
code:4
Name
WCG Clinical Inc.
Responsibilities
eCOA
Name
Scout Clinical
Responsibilities
Patient Travel and Reimbursement
Name
4g Clinical LLC
Responsibilities
code:3

Third parties

  • {"country":"Canada","full_name":"Syneos Health Clinique Inc.","duties_or_roles":"PK analysis","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"code:7","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"WCG Clinical Inc.","duties_or_roles":"eCOA","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Patient Travel and Reimbursement","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"United States","full_name":"4g Clinical LLC","duties_or_roles":"code:3","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"central ECG","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"PPD Development L.P.","duties_or_roles":"codes:1,10,11,12,13,14,2,5,6,8,9","organisation_type":"Pharmaceutical company"}
  • {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
BHV-7000
Active Substance
BHV-7000
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
1
Starting Dose
25 mg
Dose Levels
25 mg; 50 mg; 75 mg
Maximum Dose
75 mg
Dose Escalation Increase
25 mg -> 50 mg -> 75 mg
Investigational Product Name
Placebo for BHV-7000
Modality
Other
Combination Treatment
Yes

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