PCDH19-Related EpilepsyPhase 2NCT03865732
Study of Adjunctive Ganaxolone Treatment in Female Children With Protocadherin 19 (PCDH19)-Related Epilepsy (Violet Study)
A Phase 2 study testing Ganaxolone in people with PCDH19-Related Epilepsy, run by Marinus Pharmaceuticals at 12 sites in 5 countries.
Trial summary
A clinical study to evaluate the efficacy, safety, and tolerability of adjunctive ganaxolone therapy compared to placebo for the treatment of seizures in female children and young adults with genetically confirmed PCDH19 gene mutation. Read more about this study
- Who is it for?
- Ages 1 year to 17 years, women only
- Conditions the study is for
- PCDH19-Related Epilepsy
- What is being tested?
- Ganaxolone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 29 participants
- Where
- 12 sitesin 5 countries
- Study dates
- 17 May 2019to 20 Jun 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 1 year to 17 years
- Women only
- No healthy volunteers
- Child
Who may be able to join
- Molecular confirmation of a pathogenic or likely pathogenic PCDH19 variant
- Failure to control seizures despite 2 or more anti-seizure medications
- 12 seizures over a 12-week period of primary seizure types prior to screening
- On a stable regimen of concomitant AEDs, Ketogenic diets, and modified Atkins diet should be unchanged for 3 months prior to screening)
Who cannot join
- Previous exposure to ganaxolone
- > 8 consecutive weeks of seizure freedom during the 12 weeks prior to screening
- Concurrent use of strong inducers or inhibitors of CYP3A4/5/7 is not permitted
- Use of tetrahydrocannabinol (THC) or non-approved cannabidiol (CBD) is prohibited during the double-blind phase
- Exposure to any other investigational drug within 30 days or fewer than 5 half-lives prior to screening
Trial locations and contacts
12 sites in 5 countries.
12 sites in 5 countries
United States6 sites
Marinus Research Site
Durham, North Carolina, 27710
Marinus Research Site
Little Rock, Arkansas, 72202
Marinus Research Site
Los Angeles, California, 90095
Marinus Research Site
Salt Lake City, Utah, 84113
Marinus Research Site
San Francisco, California, 94158
Marinus Research Site
York, Pennsylvania, 17403
Italy2 sites
Marinus Research Site
Florence, 50139
Marinus Research Site
Rome, 00165
Netherlands2 sites
Marinus Research Site
Heeze, 5591
Marinus Research Site
Zwolle, 8025
About this study
Official title: A Double-blind, Randomized, Placebo-controlled Trial of Adjunctive Ganaxolone Treatment in Female Children With Protocadherin 19 (PCDH19)-Related Epilepsy Followed by Long-term Open-label Treatment.
A clinical study to evaluate the efficacy, safety, and tolerability of adjunctive ganaxolone therapy compared to placebo for the treatment of seizures in female children and young adults with genetically confirmed PCDH19 gene mutation.
Read the detailed description
The Violet Study is a global, double-blind, placebo-controlled, Phase 2 clinical trial that plans to enroll approximately 25 female patients between the ages of 1 and 17 with a confirmed disease-related PCDH19 gene variant. Patients will undergo a baseline period before being randomized to receive, in addition to their existing anti-seizure treatment, either ganaxolone or placebo for 17 weeks. Following the treatment period, all patients that meet certain eligibility requirements will have the opportunity to receive ganaxolone in the open label phase of the study. The study's primary efficacy endpoint is percent reduction in seizures. Secondary outcome measures will include non-seizure-related endpoints to capture certain behavioral and sleep disturbances that have been seen in previous clinical studies with ganaxolone.
- Conditions
- PCDH19-Related Epilepsy
- Being tested
- Ganaxolone, Placebo
- Keywords
- refractory seizures, epilepsy in children, seizure disorder
- Medical subject headings
- Seizures, Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GanaxoloneDrug
active drug
PlaceboDrug
Also called Placebo (for ganaxolone)
inactive
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | placebo suspension 3x's /day for 17 weeks Receives: Drug: Placebo |
| Ganaxolone | Experimental | ganaxolone suspension (50 mg/ml) 3x's /day for 17 weeks Receives: Drug: Ganaxolone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Summary of 28-day Seizure Frequency Through 17 Week Post-Baseline Phase (Median Percent Change)
Summary of 28-Day Seizure Frequency for Seizure Types through 17 week Post-Baseline Phase (Median Percent Change)
Measured: End of the double-blind 17 week treatment period
Secondary outcomes (2)
Summary of 28-day Seizure Frequency for Subjects in the Biomarker-positive Stratum (Median Percent Change)
Summary of 28-day Seizure Frequency for Seizure Types for Subjects in the Biomarker-positive Stratum through 17 weeks (Median Percent Change)
Measured: [Time Frame: End of the double-blind 17 week treatment period]
50% Primary Seizure Reduction
Percent of subjects experiencing a greater than or equal to 50% reduction in 28-day primary seizure frequency relative to the 12-week baseline
Measured: End of the double-blind 17 week treatment period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2019
- Study start17 May 2019
- Primary completion19 Jan 2021
- Study completion20 Jun 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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PCDH19-Related EpilepsyStudies 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
- Randomised
- Intervention model
- Parallel groups
- Model description
- The double-blind phase will randomize subjects to adjunctive ganaxolone or placebo at a 1:1 ratio to standard of care.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Marinus Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Maciej Gasior, M.D., Ph.D, Study director, Marinus Pharmaceuticals, Inc.Paula Bokesk, M.D., FAAP, Study director, Marinus Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03865732
- Sponsor's protocol ID
- 1042-PCDH19-3002
- Other IDs
- 2018-004496-12, 2018
- Status last verified
- Jun 2023
- First submitted
- 5 Mar 2019
- Last updated
- 26 Jun 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Sullivan J, Gunning B, Zafar M, Guerrini R, Gecz J, Kolc KL, Zhao Y, Gasior M, Aimetti AA, Samanta D. Phase 2, placebo-controlled clinical study of oral ganaxolone in PCDH19-clustering epilepsy. Epilepsy Res. 2023 Mar;191:107112. doi: 10.1016/j.eplepsyres.2023.107112. Epub 2023 Feb 22.
PubMed 36870093
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind, Randomized, Placebo-controlled Trial of Adjunctive Ganaxolone Treatment in Female Children With Protocadherin 19 (PCDH19)-Related Epilepsy Followed by Long-term Open-label Treatment.
- ClinicalTrials.gov ID
- NCT03865732
- Acronym / sponsor ID
- 1042-PCDH19-3002
- Conditions
- PCDH19-Related Epilepsy
- Keywords
- refractory seizures, epilepsy in children, seizure disorder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Marinus PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 17 May 2019 (actual)
- Primary completion
- 19 Jan 2021 (actual)
- Study completion
- 20 Jun 2022 (actual)
- First posted
- 7 Mar 2019 (actual)
- Results
- Posted 8 Sep 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A clinical study to evaluate the efficacy, safety, and tolerability of adjunctive ganaxolone therapy compared to placebo for the treatment of seizures in female children and young adults with genetically confirmed PCDH19 gene mutation.
Detailed description
The Violet Study is a global, double-blind, placebo-controlled, Phase 2 clinical trial that plans to enroll approximately 25 female patients between the ages of 1 and 17 with a confirmed disease-related PCDH19 gene variant. Patients will undergo a baseline period before being randomized to receive, in addition to their existing anti-seizure treatment, either ganaxolone or placebo for 17 weeks. Following the treatment period, all patients that meet certain eligibility requirements will have the opportunity to receive ganaxolone in the open label phase of the study. The study's primary efficacy endpoint is percent reduction in seizures. Secondary outcome measures will include non-seizure-related endpoints to capture certain behavioral and sleep disturbances that have been seen in previous clinical studies with ganaxolone.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- The double-blind phase will randomize subjects to adjunctive ganaxolone or placebo at a 1:1 ratio to standard of care.
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placeboplacebo suspension 3x's /day for 17 weeks |
| Ganaxolone | Experimental | Drug: Ganaxoloneganaxolone suspension (50 mg/ml) 3x's /day for 17 weeks |
Who may qualify
- Ages
- 1 year to 17 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Molecular confirmation of a pathogenic or likely pathogenic PCDH19 variant
- Failure to control seizures despite 2 or more anti-seizure medications
- 12 seizures over a 12-week period of primary seizure types prior to screening
- On a stable regimen of concomitant AEDs, Ketogenic diets, and modified Atkins diet should be unchanged for 3 months prior to screening)
Key exclusion criteria (5 listed)
- Previous exposure to ganaxolone
- > 8 consecutive weeks of seizure freedom during the 12 weeks prior to screening
- Concurrent use of strong inducers or inhibitors of CYP3A4/5/7 is not permitted
- Use of tetrahydrocannabinol (THC) or non-approved cannabidiol (CBD) is prohibited during the double-blind phase
- Exposure to any other investigational drug within 30 days or fewer than 5 half-lives prior to screening
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 |
|---|---|---|
| Ganaxoloneactive drug | Drug | Ganaxolone |
| PlaceboAlso: Placebo (for ganaxolone)inactive | Drug | Placebo |
Primary outcome
Summary of 28-day Seizure Frequency Through 17 Week Post-Baseline Phase (Median Percent Change)
Time frame: End of the double-blind 17 week treatment period
Summary of 28-Day Seizure Frequency for Seizure Types through 17 week Post-Baseline Phase (Median Percent Change)
2 secondary outcomes
Summary of 28-day Seizure Frequency for Subjects in the Biomarker-positive Stratum (Median Percent Change)
Time frame: [Time Frame: End of the double-blind 17 week treatment period]
50% Primary Seizure Reduction
Time frame: End of the double-blind 17 week treatment period
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36870093Sullivan J, Gunning B, Zafar M, Guerrini R, Gecz J, Kolc KL, Zhao Y, Gasior M, Aimetti AA, Samanta D. Phase 2, placebo-controlled clinical study of oral ganaxolone in PCDH19-clustering epilepsy. Epilepsy Res. 2023 Mar;191:107112. doi: 10.1016/j.eplepsyres.2023.107112. Epub 2023 Feb 22.
- Individual participant dataSharing planned: No
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.
Maciej Gasior, M.D., Ph.D study director
Marinus Pharmaceuticals, Inc.
Paula Bokesk, M.D., FAAP study director
Marinus Pharmaceuticals, Inc.
12 sites in 5 countries: 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 PCDH19-Related Epilepsy, run by Marinus Pharmaceuticals at 12 sites in 5 countries.
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 5 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 26 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States, Italy, Netherlands, Hungary, Poland. 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. Some participants in this study may receive a placebo. 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 8 Sep 2022). 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?
Summary of 28-day Seizure Frequency Through 17 Week Post-Baseline Phase (Median Percent Change) (time frame: End of the double-blind 17 week treatment period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03865732, which also lists 1 linked publication.
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 26 Jun 2023.