BHV-7000 Responsive Neurostimulation System (RNS) Study
- Conditions
- EpilepsySeizures
- Interventions
- Drug: BHV-700
- Registration Number
- NCT07125261
- Lead Sponsor
- Yale University
- Brief Summary
This is an open label study to assess the biological effect of BHV-7000 on abnormal activity recorded by the RNS System in patients with focal epilepsy implanted with the RNS System. BHV-7000 is a potassium channel activator being evaluated for use in epilepsy. Participants are offered the drug for 4 weeks. Activity during that treatment period is compared to a 90-day retrospective baseline period in which other medications and device settings were stable, and also to a 4-week withdrawal period after treatment is discontinued. The study is open to patients with RNS regardless of whether they report clinical seizures, as long as the device recordings continue to show epileptiform activity.
- Detailed Description
This is an open-label proof-of-principle study to assess the biological effect BHV-7000 on epileptiform activity detected by the RNS System. The study uses a single case experimental design in a small number of participants. Following a 90-day retrospective baseline period, there is a 4-week treatment period followed by a 4-week withdrawal period. Objective electrophysiologic biomarkers will be obtained from patients' RNS and analyzed in each participant to assess patient-level efficacy.
The primary objective of this study is to determine whether BHV-7000, a potassium channel activator, reduces the frequency of electrographic biomarkers of epileptic activity detected in patients with epilepsy who were implanted with the RNS System.
Secondary objectives are assess whether BHV-7000 withdrawal in participants leads to subsequent worsening of electrographic biomarkers of seizures compared to the treatment period, and to assess the safety and tolerability of BHV-7000 in participants with epilepsy who have been implanted with RNS.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 5
- Diagnosis of focal epilepsy as documented in the medical record.
- Implanted at least 1 year ago with RNS.
- RNS device actively recording intracranial EEG data.
- Baseline RNS recordings show that the over 50% of detections represent epileptiform seizure onset patterns.
- Provision of signed and dated informed consent form.
- Ability to take oral medication and be willing to adhere to the BHV-7000 treatment regimen.
- WOCBP may be included if they agree to use 2 methods of contraception, at least one of which is considered to be highly effective for the duration of the study (i.e., beginning 30 days prior to dosing and extending until at least 60 days post-last dose of BHV-7000.
- WOCBP must agree not to donate ova from the time of the first administration of study drug until at least 60 days post-last dose of BHV-7000.
- Fertile males may be included, but if they have a partner who is a woman of childbearing potential (WOCBP), they must agree to use 2 methods of contraception, at least one of which is considered to be highly effective for the duration of the study and extending to 120 days after the last dose of study drug. Non fertile men or men with partners who are women of non-childbearing potential (WONCBP) are not required to use contraception.
- Fertile males must agree not to donate sperm from the time of the first administration of study drug until 120 days after the last dose of study drug.
- Body mass index (BMI) < 40 kg/m² at screening visit.
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Change in any antiseizure medication (including addition or discontinuation of any antiseizure
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Any change in RNS detection settings within 90 days prior to planned treatment Day 1.
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Change in RNS stimulation settings within 90 days prior to planned drug administration (retrospective baseline period).
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Poor or inconsistent history of device downloads in the 90 days prior to planned treatment Day 1, as determined by less than 90% of episode start data being available at treatment Day 1.
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RNS battery low (estimated to last for less than 3 months).
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History or presence of any significant medical or surgical condition or uncontrolled medical illness at screening including, but not limited to, hematologic, cardiovascular, pulmonary, renal, gastrointestinal, endocrine, hepatic or urogenital systems, or other conditions that would place the participant at increased risk as determined by the PI.
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Any clinically significant laboratory abnormalities or clinically significant abnormalities on screening physical examination, vital signs, or ECG that, in the judgment of the PI, indicates a medical problem that would preclude study participation. Any significant laboratory, vital sign and examination abnormality should be discussed with the Sponsor medical monitor before including the participant. Some specific laboratory abnormalities that would fall in this category include:
a. Estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2 b. Hematologic abnormalities at screening: i. Hemoglobin ≤ 10 g/dL; or ii. WBC < 3.0 x 10³/mm³; or iii. Platelet count < 100,000 cell/mm³; or iv. Neutrophils, Absolute ≤ 1000 cell/mm³ c. Hemoglobin A1C > 7.0% d. Screening ALT, AST > 2, or total bilirubin > 1.5 x upper limit of reference range (one re-test is allowed prior to baseline/randomization): e. Participants with chronically, stable (for > 6 months) elevated liver enzymes that are ≤ 3 x ULN that is related to ASM treatment may be eligible determined by discussion with Medical Monitor.
f. Participants with diagnosis of Gilbert's syndrome may be included with Medical Monitor approval.
g. A positive test for HBsAg, HCV Ab, or HIV- 1/2 Ag/Ab at screening. h. A positive pregnancy test.
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Schizophrenia and other psychotic disorders (e.g., schizophreniform disorder, schizoaffective disorder, psychosis not otherwise specified [NOS]), bipolar disorder, and/or obsessive-compulsive disorder, or other serious mental health disorders. Uncontrolled unipolar major depression where changes in pharmacotherapy are needed or anticipated during the study.
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Active suicidal plan/intent in the past six months, a suicide attempt in the last two years, or more than one lifetime suicide attempt.
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Females who are pregnant, breastfeeding, or planning to become pregnant from screening until 60 days post-last dose of BHV-7000.
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History of illicit drug or alcohol abuse within one year prior to screening judged by the PI to be excessive or compulsive, or currently using drugs of abuse or any prescribed or over the counter medication in a manner that the PI considers indicative of abuse or dependence.
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Participants taking strong or moderate CYP3A4 inhibitors or strong inducers. If the participant is on a strong or moderate inhibitor or strong inducer of CYP3A4, an alternate drug must be sought.
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Exposure to any other investigational drug or device within five half-lives or 30 days prior to screening, whichever is longer.
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History of cancer within the past two years, with the exception of appropriately treated basal cell or squamous cell carcinoma.
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History of recurrent severe constipation, fecal impaction, or gastrointestinal obstruction requiring hospitalization.
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History of clinically significant urinary retention in the judgment of the PI.
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Previous exposure to BHV-7000 or known allergy to BHV-7000 or its excipients.
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Any major surgery within one month or an acute illness within two weeks prior to screening.
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Vaccination within the previous four weeks prior to screening or planned vaccination during the study.
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History of ezogabine use.
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Known allergic reactions to components of the study drug.
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Febrile illness within 90 days prior to planned treatment Day 1.
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Presence of any retinal abnormality on baseline ophthalmic examination.
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Significant cardiovascular history, including but not limited to uncontrolled angina, myocardial infarction (Ml) within 12 months of screening, clinically significant arrhythmia, congestive heart failure (New York Heart Association [NYHA] Class Ill or higher).
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QTcF (Fridericia) interval 450 msec for males and 470 msec for females; Mobitz Type II second or third degree atrioventricular (AV) block, or complete left bundle branch block, or complete right bundle branch block, or intraventricular conduction defect with a QRS duration 130 msec, or evidence of acute or sub-acute myocardial infarction (Ml) or ischemia, or other ECG findings that, in the investigator's opinion, would preclude participation in the study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description BHV-7000 BHV-700 Participants will receive up to 28 days of study drug and will be followed clinically until Day 56, making their total involvement in the study up to 84 days. The study follows an ABA treatment paradigm with (A) 90-day retrospective RNS baseline, (B) 4-week treatment period, and (A) 4-week withdrawal period.
- Primary Outcome Measures
Name Time Method Reduction in patient-specific seizure surrogate rate 28 days Per-participant percentage reduction in patient-specific seizure surrogate rate in the treatment period relative to retrospective baseline.
Reduction in seizure onset pattern rate 28 days Per-participant percentage reduction in seizure onset pattern rate in the treatment period relative to retrospective baseline.
Reduction in long episode rate 28 days Per-participant reduction in long episode rate during the treatment period relative to the retrospective baseline.
Reduction in saturation rate 28 days Per-participant reduction in saturation rate during the treatment period relative to the retrospective baseline, for those patients who have saturations.
- Secondary Outcome Measures
Name Time Method Withdrawal effect on seizure onset pattern rate 4 weeks post 28-day treatment Change in seizure onset pattern rate following drug withdrawal.
Withdrawal effect on patient-specific seizure surrogate rate 4 weeks post 28-day treatment Change in patient-specific seizure surrogate rate following drug withdrawal.
Withdrawal effect on long episode rate 4 weeks post 28-day treatment Change in long episode rate following drug withdrawal.
Number of Participants With Treatment-Related Laboratory Abnormalities or Adverse Events of Special Interest (AESI) as Assessed by CTCAE/DAIDS up to 12 weeks Treatment-emergent laboratory abnormalities and AESIs will be reported. Higher score corresponding to increasing AE severity.
Trial Locations
- Locations (1)
Yale Comprehensive Epilepsy Center
🇺🇸New Haven, Connecticut, United States
Yale Comprehensive Epilepsy Center🇺🇸New Haven, Connecticut, United States