Adjunctive Ganaxolone Treatment (Part A) in TSC Followed by Long-term Treatment (Part B)

Brief Title

Adjunctive Ganaxolone Treatment (Part A) in TSC Followed by Long-term Treatment (Part B)

Official Title

A Phase 2 Open-label 12-Week Trial of Adjunctive Ganaxolone Treatment (Part A) in Tuberous Sclerosis Complex-related Epilepsy Followed by Long-term Treatment (Part B)

Brief Summary

      To assess preliminary safety and efficacy of ganaxolone as adjunctive therapy for the
      treatment of primary seizure types in patients with genetically- or clinically-confirmed
      TSC-related epilepsy through the end of the 12 week treatment period.
    

Detailed Description

      This is an OL proof of concept study of adjunctive GNX treatment in patients with a confirmed
      clinical diagnosis of TSC and/or a mutation in either the TSC1 or TSC2 gene. The trial
      consists of two parts: Part A consists of a 4-week baseline period followed by a 12-week
      treatment period (4-week titration and 8-week maintenance). For patients not continuing in
      the 24-week OLE period (Part B), a 2-week taper period followed by a 2-week safety period
      would follow. The main difference between Part A and Part B is the length of treatment, less
      frequent assessments, and the ability to alter drug doses (both GNX and other antiepileptic
      drug [AED] treatments which includes initiating and stopping other medications) based on
      investigator evaluation of the patient's clinical course during Part B. Patients with a
      seizure frequency reduction during the 12-week treatment period in Part A compared to
      baseline may continue into Part B ("OLE eligible"), to assess long-term safety, efficacy and
      tolerability in patients with TSC-related Epilepsy.
    

Study Phase

Phase 2

Study Type

Interventional

Primary Outcome

Percent Change in 28-day Seizure Frequency

Secondary Outcome

 Percentage of patients

Condition

Tuberous Sclerosis

Intervention

Ganaxolone

Study Arms / Comparison Groups

 Open-label

Description:  ganaxolone suspension (50 mg/ml) TID for 12 weeks with 24 week extension

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

24

Start Date

April 8, 2020

Completion Date

December 31, 2021

Primary Completion Date

June 30, 2021

Eligibility Criteria

        Inclusion Criteria (Part A):

          -  Clinical or mutational diagnosis of TSC

          -  Failure to control seizures despite appropriate trial of 2 or more ASMs at therapeutic
             doses.

          -  Have at least 8 countable/witnessed primary seizures during the 4-week baseline period
             with at least 1 primary seizure occurring in at least 3 of the 4 weeks of baseline.

        Inclusion Criteria (Part B)

        • Patients have experienced ≥ 35% reduction in primary seizure frequency during the Part A
        treatment period compared to the 4-week Baseline Period.

        Exclusion Criteria (Part A):

          -  Previous exposure to GNX

          -  Pregnant or breastfeeding

          -  Concurrent use of strong inducers or inhibitors of cytochrome P450 (CYP)3A4/5/7. Any
             strong inhibitor or inducer of CYP3A4/5/7 must be discontinued at least 28 days before
             Visit 2, study drug initiation. This does not include approved ASMs.

          -  Patients who have been taking felbamate for less than 1 year prior to screening

          -  Patients who test positive for tetrahydrocannabinol (THC) or non-approved cannabidiol
             (CBD) via plasma drug screen

          -  Chronic use of oral steroid medications, ketoconazole (except for topical
             formulations), St. John's Wort, or other IPs is not permitted

          -  Have an active CNS infection, demyelinating disease, degenerative neurological
             disease, or CNS disease deemed progressive. This includes tumor growth which in the
             opinion of the investigator could affect primary seizure control

          -  Patients with significant renal insufficiency, estimated glomerular filtration rate
             (eGFR) < 30 mL/min (calculated using the Cockcroft-Gault formula or Pediatric GFR
             calculator or Bedside Schwartz), will be excluded from study entry or will be
             discontinued if the criterion is met post baseline

          -  Have been exposed to any other investigational drug within 30 days or fewer than 5
             half lives (whichever is shorter) prior to the screening visit
      

Gender

All

Ages

2 Years - 65 Years

Accepts Healthy Volunteers

No

Contacts

Maciej Gasior, MD, , 

Location Countries

United States

Location Countries

United States

NCT ID

NCT04285346

Organization ID

1042-TSC-2001

Responsible Party

Sponsor

Study Sponsor

Marinus Pharmaceuticals

Study Sponsor

Maciej Gasior, MD, Study Director, Marinus Pharmaceuticals, Inc.

Verification Date

May 2021