Tuberous SclerosisPhase 2TSCNCT04285346
Adjunctive Ganaxolone Treatment (Part A) in TSC Followed by Long-term Treatment (Part B)
A Phase 2 study testing Ganaxolone in people with Tuberous Sclerosis, run by Marinus Pharmaceuticals at 7 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 to 65 years
- Conditions the study is for
- Tuberous Sclerosis
- What is being tested?
- Ganaxolone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 7 sitesUnited States
- Study dates
- 8 Apr 2020to 30 Aug 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
- Patients have experienced ≥ 35% reduction in primary seizure frequency during the Part A treatment period compared to the 4-week Baseline Period.
Who cannot join
- 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
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- 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
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Marinus Research Site
Boston, Massachusetts, 02115
Marinus Research Site
Cincinnati, Ohio, 45229
Marinus Research Site
Durham, North Carolina, 27710
Marinus Research Site
Houston, Texas, 77030
Marinus Research Site
Livingston, New Jersey, 07039
Marinus Research Site
Los Angeles, California, 90095
Marinus Research Site
Palo Alto, California, 94304
About this study
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)
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.
Read the 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.
- Conditions
- Tuberous Sclerosis
- Being tested
- Ganaxolone
- Medical subject headings
- Tuberous Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GanaxoloneDrug
titration followed by maintenance and extension period
| Study group | Role | What they receive |
|---|---|---|
| Open-label | Other | ganaxolone suspension (50 mg/ml) TID for 12 weeks with 24 week extension Receives: Drug: Ganaxolone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change From Baseline in 28-day Seizure Frequency Through the End of 12-Week Treatment Period
Primary seizures include atonic/drop, bilateral clonic, bilateral tonic, focal motor without impairment of consciousness or awareness, focal (motor or non-motor) with impairment of consciousness or awareness, focal to bilateral tonic-clonic, generalized tonic-clonic. Baseline 28-day seizure frequency was calculated as the total number of primary seizures in the Baseline period divided by the number of days with non-missing seizure data in the Baseline period, multiplied by 28. The Baseline Visit was defined as Week 0. Percent change from Baseline in 28-day seizure frequent was calculated as the difference in post-Baseline 28-day seizure frequency and Baseline 28-day seizure frequency, divided by Baseline 28-day seizure frequency, multiplied by 100.
Measured: Baseline and Up to Week 12
Secondary outcomes (1)
Percentage of Participants Experiencing a >=50 Percent Reduction in 28-day Primary Seizure Frequency Through the End of the 12-week Treatment Period Compared to the Baseline Period
Primary seizures include atonic/drop, bilateral clonic, bilateral tonic, focal motor without impairment of consciousness or awareness, focal (motor or non-motor) with impairment of consciousness or awareness, focal to bilateral tonic-clonic, generalized tonic-clonic. Percentage of participants reporting >=50 percent reduction in seizure frequency has been presented.
Measured: Baseline and up to 12 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2020
- Study start8 Apr 2020
- Primary completion25 Jun 2021
- Study completion30 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Tuberous SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Marinus Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04285346
- Sponsor's protocol ID
- 1042-TSC-2001
- Acronym
- TSC
- Status last verified
- Mar 2023
- First submitted
- 18 Feb 2020
- Last updated
- 4 Apr 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04285346
- Acronym / sponsor ID
- TSC / 1042-TSC-2001
- Conditions
- Tuberous Sclerosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Marinus PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 8 Apr 2020 (actual)
- Primary completion
- 25 Jun 2021 (actual)
- Study completion
- 30 Aug 2022 (actual)
- First posted
- 26 Feb 2020 (actual)
- Results
- Posted 4 Apr 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Open-label | Other | Drug: Ganaxoloneganaxolone suspension (50 mg/ml) TID for 12 weeks with 24 week extension |
Who may qualify
- Ages
- 2 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
- Patients have experienced ≥ 35% reduction in primary seizure frequency during the Part A treatment period compared to the 4-week Baseline Period.
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ganaxolonetitration followed by maintenance and extension period | Drug | Open-label |
Primary outcome
Percent Change From Baseline in 28-day Seizure Frequency Through the End of 12-Week Treatment Period
Time frame: Baseline and Up to Week 12
Primary seizures include atonic/drop, bilateral clonic, bilateral tonic, focal motor without impairment of consciousness or awareness, focal (motor or non-motor) with impairment of consciousness or awareness, focal to bilateral tonic-clonic, generalized tonic-clonic. Baseline 28-day seizure frequency was calculated as the total number of primary seizures in the Baseline period divided by the number of days with non-missing seizure data in the Baseline period, multiplied by 28. The Baseline Visit was defined as Week 0. Percent change from Baseline in 28-day seizure frequent was calculated as the difference in post-Baseline 28-day seizure frequency and Baseline 28-day seizure frequency, divided by Baseline 28-day seizure frequency, multiplied by 100.
1 secondary outcome
Percentage of Participants Experiencing a >=50 Percent Reduction in 28-day Primary Seizure Frequency Through the End of the 12-week Treatment Period Compared to the Baseline Period
Time frame: Baseline and up to 12 Weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ganaxolone in people with Tuberous Sclerosis, run by Marinus Pharmaceuticals at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Apr 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change From Baseline in 28-day Seizure Frequency Through the End of 12-Week Treatment Period (time frame: Baseline and Up to Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Apr 2023.