BHV-7000 for Epilepsy (RISE 2 Trial)
Recruiting in Palo Alto (17 mi)
+115 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2 & 3
Recruiting
Sponsor: Biohaven Therapeutics Ltd.
Prior Safety Data
Trial Summary
What is the purpose of this trial?The purpose of this study is to determine whether BHV-7000 is effective in the treatment of refractory focal epilepsy.
How does the drug BHV-7000 differ from other epilepsy treatments?
BHV-7000 is unique because it targets the GABA system, which plays a crucial role in controlling brain activity, and aims to develop more innovative therapies for epilepsy by focusing on this system. This approach is different from many existing treatments that also target GABA but may not be as innovative in their mechanisms.
12345Will I have to stop taking my current medications?
The trial does not specify if you need to stop your current medications, but it mentions that participants should be on at least 1 and up to 3 anti-seizure medications. It seems like you can continue your current treatment.
Eligibility Criteria
This trial is for adults aged 18-75 with refractory focal onset epilepsy, who have tried at least two anti-seizure medications without success. Participants should be able to track their seizures and may be on up to three anti-seizure meds plus one additional treatment like a diet regimen or device.Inclusion Criteria
I was diagnosed with Focal Onset Epilepsy over a year ago.
I experience seizures that start in one area of my brain.
My epilepsy is drug-resistant according to the 2009 ILAE definition.
I am currently on 1-3 seizure medications and have tried up to 4 treatments in total.
You can keep a detailed record of your seizures.
I am between 18 and 75 years old.
You have been diagnosed with Focal Epilepsy
Subjects must agree to provide all requested demographic information (i.e., biological sex at birth, race, ethnicity (ethnicity collected in US only)).
Subject and/or caregiver must be able to read and understand eDiary in an available language.
Subjects must be able to swallow the BHV-7000 IP tablet whole.
Male and Female subjects 18 to 75 years of age at time of consent.
You have been diagnosed with Focal Epilepsy
You have been diagnosed with Focal Seizures
Drug Resistant Focal Onset Seizures: Subject meets the 2009 ILAE definition of drug resistant epilepsy, failure of adequate trials of two tolerated and appropriately chosen and used anti-seizure medications schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom.
An average of 4 or more observable focal seizures per month (28 days) during the 3 months prior to the screening visit
Current treatment with at least 1 and up to 3 ASMs as part of no more than 4 stable epilepsy treatments combined.
ASMs must have a stable dose(s) for at least 1 month prior to the screening visit and ASM(s) present at screening visit must remain stable during participation in the study.
Exclusion Criteria
Subjects who are detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness.
Participant Groups
The study is testing the effectiveness and safety of BHV-7000 compared to a placebo in treating refractory focal epilepsy. Patients will either receive BHV-7000 or an inactive substance (placebo) without knowing which one they are taking.
3Treatment groups
Experimental Treatment
Placebo Group
Group I: BHV-7000 50 mgExperimental Treatment1 Intervention
Group II: BHV-7000 25 mgExperimental Treatment1 Intervention
Group III: PlaceboPlacebo Group1 Intervention
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Stony Brook MedicineStony Brook, NY
OSUColumbus, OH
Barrow Neurological InstitutePhoenix, AZ
University of California, Los AngelesLos Angeles, CA
More Trial Locations
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Who is running the clinical trial?
Biohaven Therapeutics Ltd.Lead Sponsor
References
Progress report on new antiepileptic drugs: a summary of the Eigth Eilat Conference (EILAT VIII). [2018]The Eigth Eilat Conference on New Antiepileptic Drugs (AEDs)-EILAT VII, took place in Sitges, Barcelona from the 10th to 14th September, 2006. Basic scientists, clinical pharmacologists and neurologists from 24 countries attended the conference, whose main themes included a focus on status epilepticus (epidemiology, current and future treatments), evidence-based treatment guidelines and the potential of neurostimulation in refractory epilepsy. Consistent with previous formats of this conference, the central part of the conference was devoted to a review of AEDs in development, as well as updates on marketed AEDs introduced since 1989. This article summarizes the information presented on drugs in development, including brivaracetam, eslicarbazepine acetate (BIA-2-093), fluorofelbamate, ganaxolone, huperzine, lacosamide, retigabine, rufinamide, seletracetam, stiripentol, talampanel, valrocemide, JZP-4, NS1209, PID and RWJ-333369. Updates on felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine and new extended release oxcarbazepine formulations, pregabalin, tiagabine, topiramate, vigabatrin, zonisamide and new extended release valproic acid formulations, and the antiepileptic vagal stimulator device are also presented.
Progress report on new antiepileptic drugs: A summary of the Thirteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XIII). [2018]The Thirteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XIII) took place in Madrid, Spain, on June 26-29, 2016, and was attended by >200 delegates from 31 countries. The present Progress Report provides an update on experimental and clinical results for drugs presented at the Conference. Compounds for which summary data are presented include an AED approved in 2016 (brivaracetam), 12 drugs in phase I-III clinical development (adenosine, allopregnanolone, bumetanide, cannabidiol, cannabidivarin, 2-deoxy-d-glucose, everolimus, fenfluramine, huperzine A, minocycline, SAGE-217, and valnoctamide) and 6 compounds or classes of compounds for which only preclinical data are available (bumetanide derivatives, sec-butylpropylacetamide, FV-082, 1OP-2198, NAX 810-2, and SAGE-689). Overall, the results presented at the Conference show that considerable efforts are ongoing into discovery and development of AEDs with potentially improved therapeutic profiles compared with existing agents. Many of the drugs discussed in this report show innovative mechanisms of action and many have shown promising results in patients with pharmacoresistant epilepsies, including previously neglected rare and severe epilepsy syndromes.
Targeted Augmentation of Nuclear Gene Output (TANGO) of Scn1a rescues parvalbumin interneuron excitability and reduces seizures in a mouse model of Dravet Syndrome. [2022]Dravet Syndrome (DS) is a severe developmental and epileptic encephalopathy typically caused by loss-of-function de novo mutations in the SCN1A gene which encodes the voltage-gated sodium channel isoform NaV1.1. Decreased NaV1.1 expression results in impaired excitability of inhibitory interneurons and seizure onset. To date, there are no clinically available treatments for DS that directly address the core mechanism of disease; reduced NaV1.1 expression levels in interneurons. Recently, Targeted Augmentation of Nuclear Gene Output (TANGO) of SCN1A by the antisense oligonucleotide (ASO) STK-001, was shown to increase Scn1a mRNA levels, increase NaV1.1 protein expression, reduce seizures, and improve survival in the Scn1a+/- mouse model of DS. However, it remains unknown whether STK-001 treatment rescues the reduced intrinsic excitability of parvalbumin-positive (PV) inhibitory interneurons associated with DS. In this study, we demonstrate that STK-001 treatment reduces seizures, prolongs survival, and rescues PV interneuron excitability in Scn1a+/- mice to levels observed in WT littermates. Together, these results support the notion that TANGO-mediated augmentation of NaV1.1 levels directly targets and rescues one of the core disease mechanisms of DS.
Progress report on new antiepileptic drugs: A summary of the Sixteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVI): I. Drugs in preclinical and early clinical development. [2022]The Eilat Conferences have provided a forum for discussion of novel treatments of epilepsy among basic and clinical scientists, clinicians, and representatives from regulatory agencies as well as from the pharmaceutical industry for 3 decades. Initially with a focus on pharmacological treatments, the Eilat Conferences now also include sessions dedicated to devices for treatment and monitoring. The Sixteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVI) was held in Madrid, Spain, on May 22-25, 2022 and was attended by 157 delegates from 26 countries. As in previous Eilat Conferences, the core of EILAT XVI consisted of a sequence of sessions where compounds under development were presented and discussed. This progress report summarizes preclinical and, when available, phase 1 clinical data on five different investigational compounds in preclinical or early clinical development, namely GAO-3-02, GRT-X, NBI-921352 (formerly XEN901), OV329, and XEN496 (a pediatric granular formulation of retigabine/ezogabine). Overall, the data presented in this report illustrate novel strategies for developing antiseizure medications, including an interest in novel molecular targets, and a trend to pursue potential new treatments for rare and previously neglected severe epilepsy syndromes.
New GABA-Targeting Therapies for the Treatment of Seizures and Epilepsy: II. Treatments in Clinical Development. [2023]The inhibitory neurotransmitter γ-aminobutyric acid (GABA) plays an important role in the modulation of neuronal excitability, and a disruption of GABAergic transmission contributes to the pathogenesis of some seizure disorders. Although many currently available antiseizure medications do act at least in part by potentiating GABAergic transmission, there is an opportunity for further research aimed at developing more innovative GABA-targeting therapies. The present article summarises available evidence on a number of such treatments in clinical development. These can be broadly divided into three groups. The first group consists of positive allosteric modulators of GABAA receptors and includes Staccato® alprazolam (an already marketed benzodiazepine being repurposed in epilepsy as a potential rescue inhalation treatment for prolonged and repetitive seizures), the α2/3/5 subtype-selective agents darigabat and ENX-101, and the orally active neurosteroids ETX155 and LPCN 2101. A second group comprises two drugs already marketed for non-neurological indications, which could be repurposed as treatments for seizure disorders. These include bumetanide, a diuretic agent that has undergone clinical trials in phenobarbital-resistant neonatal seizures and for which the rationale for further development in this indication is under debate, and ivermectin, an antiparasitic drug currently investigated in a randomised double-blind trial in focal epilepsy. The last group comprises a series of highly innovative therapies, namely GABAergic interneurons (NRTX-001) delivered via stereotactic cerebral implantation as a treatment for mesial temporal lobe epilepsy, an antisense oligonucleotide (STK-001) aimed at upregulating NaV1.1 currents and restoring the function of GABAergic interneurons, currently tested in a trial in patients with Dravet syndrome, and an adenoviral vector-based gene therapy (ETX-101) scheduled for investigation in Dravet syndrome. Another agent, a subcutaneously administered neuroactive peptide (NRP2945) that reportedly upregulates the expression of GABAA receptor α and β subunits is being investigated, with Lennox-Gastaut syndrome and other epilepsies as proposed indications. The diversity of the current pipeline underscores a strong interest in the GABA system as a target for new treatment development in epilepsy. To date, limited clinical data are available for these investigational treatments and further studies are required to assess their potential value in addressing unmet needs in epilepsy management.