A Phase 2, Global, Multicenter, Long-term Safety Study Designed to Assess the Safety and Tolerability of BHV-7000 in Subjects with Refractory Focal Onset Epilepsy

A Phase 2, Global, Multicenter, Long-term Safety Study Designed to Assess the Safety and Tolerability of BHV-7000 in Subjects with Refractory Focal Onset Epilepsy

Epilepsy is a neurological disease associated with unprovoked seizures along with abnormal electrical activity in the brain. Seizures are only one part of epilepsy, as patients are faced with frequent comorbidities such as depression, anxiety, and attention problems, all of which can have a significant negative impact on quality of life. The World Health Organization (WHO) Global Burden of Disease Study from 2016 ranks idiopathic epilepsy among the top 5 most burdensome neurologic disorders worldwide in terms of disability-adjusted life years.

BHV-7000 is a next-generation molecule and is highly differentiated from ezogabine, a first-generation non-selective Kv7 activator broadly active across preclinical models of epilepsy that was previously approved for adjunctive treatment of partial-onset seizures in adults and has shown promise for the treatment of mood disorders. In comparison with ezogabine, and ezogabine analogues, BHV-7000 belongs to a significantly different structural class and was rationally designed to differentiate from ezogabine on key properties, including pharmacology, plasma stability, GABAA receptor positive allosteric modulation (PAM), and stability to photooxidation. Importantly, BHV-7000 does not exhibit the GABAA receptor PAM activity seen with ezogabine and some other ASMs, which may contribute to their poor tolerability observed both non-clinically and clinically.

Male and female subjects, 18 – 75 years of age at the time of entry into the double-blind (DB) parent study BHV7000-303. Eligible subjects must have completed the DB phase of the parent study, and must in the opinion of the investigator, have a favorable risk-benefit profile to continue in this long-term safety study.

This is a Phase 2, global, multicenter, long-term safety study designed to assess the safety and tolerability of BHV-7000 in participants with focal refractory epilepsy. Approximately 660 eligible subjects will enter this study after completing the DBP of either the BHV7000-302 (not completed in India) or BHV7000-303 studies.

In the opinion of the investigator, subjects must have tolerated BHV-7000/placebo, during participation in the DBP of the parent study BHV7000-303 to be eligible.

Eligible subjects who completed the DBP of BHV7000-303 study will be initially assigned BHV-7000 75 mg dose at the baseline visit (75 mg dose is comprised of one ER tablet 50 mg and one ER tablet 25 mg). All subjects will have the opportunity to take BHV-7000 for 52 weeks.

Dose modifications of BHV-7000 should be avoided during the study but are permitted if deemed medically necessary by the Investigator.

In addition, modifications to epilepsy treatments should be avoided, but are allowed if deemed medically necessary by the Investigator. It is recommended that the subject should be treated with BHV-7000 for a minimum of approximately 6 weeks after entry into this study PRIOR to any modifications to the current epilepsy treatments (i.e., other ASM dose or frequency, dietary therapy, and neurostimulation parameters). Subjects will continue to report each seizure occurrence and classification throughout the study, via a similar electronic diary (eDiary) as was utilized in the DBP of the parent study BHV7000-303.

Subjects will have in-clinic study visits at weeks 2, 6, 10, 18, 26, 40, and 52 (with telephone visits at weeks 4 and 32) and will enter the follow-up phase for an in-clinic assessment approximately 2 weeks after last dose of investigational product (IP). Subjects will be regularly monitored for safety including laboratory assessments, ECGs, physical exams, neurological exams, the C-SSRS, and monitoring of AEs.

In addition to the regular monitoring for safety parameters, subjects will be assessed for proper use of IP, concomitant medications, including ASMs, and seizure occurrence and classification.

The last visit of the DBP of the prior parent study (week 8 of BHV7000-303) is the same day as the baseline visit for this study. The informed consent for this study includes a statement that examinations and results from the end of treatment visit in the prior parent study may be utilized in this study, where applicable, to avoid duplication of assessments and examinations. The utilization of these examinations and results will only be applied once the informed consent for BHV7000-201 has been signed and agreed by the subject or the caregiver.

A significant unmet medical need exists for effective agents with a favorable tolerability profile, especially those with a novel mechanism of action that is complementary to currently available ASMs. BHV-7000 is being developed by Biohaven for the treatment of focal onset epilepsy.