Anti-Epilepsy Medication Valproate Administered Via ICV Route and Catheters and Pumps for CSF Infusion

An Open-Label Extension Study to Investigate the Long-Term Safety, and Tolerability of Intracerebroventricular (ICV) Delivery of Valproate in Subjects With Focal Seizures, With Temporal Lobe Onset With or Without Secondary Generalization

This is a non-randomized open-label extension study for subjects having completed protocol DA071976 or CLN100P.01.

Study Overview

• Status: Terminated
• Conditions: Focal Epilepsy
• Intervention / Treatment: Drug: Valproic Acid delivered to ICV

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Brisbane, New South Wales, Australia
      • Mater Brisbane
    • Brisbane, New South Wales, Australia
      • RBWH
  • Victoria
    • Melbourne, Victoria, Australia
      • The Alfred
    • Melbourne, Victoria, Australia
      • SVHM
    • Melbourne, Victoria, Australia
      • The Austin
• Israel
  • Jerusalem, Israel
    • Hadassah Medical Center
  • Jerusalem, Israel
    • Sheeba Medical Center
  • Tel Aviv, Israel
    • Tel Aviv Sourasky Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Completed the DA07976 or CLN100P.01 Study
2. In the opinion of the investigator, if the subject were to be removed from study and associated therapy, subject would have worsening/increase in disabling seizures. Disabling refers to seizures that are severe enough to cause injuries, or significantly impair functional ability in domains including employment, psychosocial education and mobility.
3. Subject is taking currently approved AED medication(s) (but is not on valproate or divalproex sodium).
4. Subject has seizures that are distinct, stereotypical events that can be reliably counted, in the opinion of the Investigator, by the subject or caregiver.
5. Subject has hearing, vision, and physical abilities adequate to perform assessments, with or without corrective aids, including keeping a seizure and medication diary during study follow-up.
6. Subject understands study procedures and has voluntarily provided signed, informed consent in accordance with institutional and local regulatory requirements.
7. Needs be literate in English or native language of the country of the study enrollment to complete neuropsychological testing.
8. Subject can be reasonably expected to maintain a seizure diary alone or with the assistance of a competent individual.
9. Women of childbearing potential must be using a medically accepted method of contraception and have a negative qualitative β-human chorionic growth hormone (β-HCG) pregnancy test result from a urine or blood sample collected per SOE.

Exclusion Criteria:

• 1. Subject has any significant neurologic disease other than epilepsy. 2. Subject has had status epilepticus refractory to benzodiazepines and phenytoin in the past year 3. Subject is currently taking oral valproic acid or sodium divalproex. 4. Subject has known allergy to valproic acid, divalproex sodium, Epilim, or Depacon.

  5. Subject has unstable depression or any major psychiatric disorder including psychosis, major depression, bipolar disorder that in the opinion of the Investigator would put the subject at risk as a participant in the study.

  6. Subject has history or evidence of congestive heart failure, clinically significant peripheral edema, or anemia with a hematocrit <30%.

  7. Subject has current diagnosis of cancer requiring treatment. 8. Subject in the opinion of the Investigator, is not a suitable candidate for cranial surgery for any reason.

  9. Subject has known HIV infection or known or suspected prion disease. 10. Subject has known allergies to drugs or excipients. 11. Subject is breastfeeding, pregnant, or expressed intent on becoming pregnant during the course of the study and Investigator feels pregnancy is a likely outcome during the study 12. In the opinion of the investigator, the subject has a clinically significant or unstable medical condition (including alcohol and/or drug abuse) or a progressive CNS disease that in the opinion of the Investigator would put the subject at risk as a participant in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open-Label Safety; Participants roll-over from DA071976 or CLN100P.02	Drug: Valproic Acid delivered to ICV; Valproic Acid delivered to ICV via an implantable pump and catheter system

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety measured as drug or device related SAEs	The primary objective is to assess long-term safety and tolerability of ICV delivery of Valproate as measured by drug and device related adverse events.	2-years

Collaborators and Investigators

• Sponsor: Cerebral Therapeutics LLC

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Actual): March 1, 2024
• Study Completion (Actual): March 1, 2024

Study Registration Dates

• First Submitted: August 25, 2020
• First Submitted That Met QC Criteria: August 25, 2020
• First Posted (Actual): August 28, 2020

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Epilepsies, Partial; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Tranquilizing Agents; Psychotropic Drugs; GABA Agents; Anticonvulsants; Antimanic Agents; Valproic Acid
• Other Study ID Numbers: CLN100P.02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes