EpilepsyPhase 2NCT02358538

Open-Label PoC Trial of Ganaxolone in Children With PCDH19 Female Pediatric Epilepsy and Other Rare Genetic Epilepsies

A Phase 2 study testing Ganaxolone in people with Epilepsy, run by Marinus Pharmaceuticals at 10 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

To evaluate the efficacy of open-label ganaxolone as adjunctive therapy for uncontrolled seizures in female children with PCDH19 mutation and other rare genetic epilepsies in an open-label proof-of-concept study. Read more about this study

Who is it for?: Ages 2 to 18 years
Conditions the study is for: Epilepsy
What is being tested?: Ganaxolone
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 30 participants
Where: 10 sitesin 2 countries
Study dates: 6 Nov 2015to 4 Jan 2019
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 18 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

Have parent or legal guardian available and willing to give written informed consent.
Male and female outpatients between 2 and 18 years of age years of age at time of consent.
Have any of the following epilepsy syndromes: PCDH19; CDKL5; Dravet Syndrome; Lennox Gastaut Syndrome (LGS); Continuous Spikes and Waves during Sleep (CSWS)
Have uncontrolled cluster seizures and/or non-clustered seizures.
Subjects should be on a stable regimen of anti-epileptic medication, and generally in good health.
Parent or guardian is able and willing to maintain an accurate and complete daily written seizure calendar.
Able and willing to take study medication with food, two or three times daily.

Who cannot join

Have had previous exposure to ganaxolone.
Known sensitivity or allergy to any component in the study drug, progesterone, or other related steroid compounds.
Exposure to any investigational drug or device < 90 days prior to screening, or plans to participate in another drug or device trial at any time during the study.
Concurrent use of vigabatrin, tiagabine, or ezogabine is not permitted.
Have any medical condition that, in the investigator's judgment, is considered to be clinically significant and could potentially affect subject safety or study outcome, including but not limited to: clinically significant cardiac, renal, pulmonary, gastrointestinal, hematologic or hepatic conditions; or a condition that affects the absorption, distribution, metabolism or excretion of drugs.
Have active suicidal plan/intent, or have had active suicidal thoughts in the past 6 months or a suicide attempt in the past 3 years.
Have Alanine transferase (ALT; SGPT) or Aspartate transferase (AST; SGOT) levels > 3 times upper limits of normal (ULN), or total bilirubin >1.5 time ULN at the screening and baseline visits.

Trial locations and contacts

10 sites in 2 countries.

Country

City, postcode or hospital

10 sites in 2 countries

United States9 sites

Boston Children's Hospital
Boston, Massachusetts, 02115
Nationwide Children's Hospital
Columbus, Ohio, 43205
Northeast Regional Epilepsy Group
Hackensack, New Jersey, 07601
JWM Neurology
Indianapolis, Indiana, 46239
Institute of Neurology and Neurosurgery at St. Barnabas
Livingston, New Jersey, 07039
Center for Rare Neurological Diseases
Norcross, Georgia, 30093
Phoenix Children's Hospital
Phoenix, Arizona, 85016
Sutter Institute for Medical Research
Sacramento, California, 95816
University of California San Francisco
San Francisco, California, 94143

Other trials in United States

Italy1 site

Bambino Gesu Children's Hospital, IRCCS
Rome, 00165

Other trials in Italy

About this study

Official title: A Multicenter, Open-Label Proof-of-Concept Trial of Ganaxolone in Children With PCDH19 Female Pediatric Epilepsy and Other Rare Genetic Epilepsies Followed by 52 Week Open-Label Treatment

Read the detailed description

The purpose of this proof-of-concept study is to evaluate ganaxolone as adjunctive therapy for uncontrolled seizures in female children with PCDH19 mutations and other rare genetic epilepsies. After establishing baseline seizure frequency, qualifying subjects will enter the study and be treated with open-label ganaxolone for up to six months.

Conditions: Epilepsy
Being tested: Ganaxolone
Keywords: PCDH19, ganaxolone, neurosteroid, CDKL5, LGS, CSWS
Medical subject headings: Epilepsy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

GanaxoloneDrug
Also called CCD 1042
oral suspension or capsules

Study groups in NCT02358538
Study group	Role	What they receive
Ganaxolone	Experimental	Maximum of 1800 mg/day or 63 mg/kg/day 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 for Sum of Individual Seizures and Clusters for 52-week OLE Period (Mean Percent Change & Standard Deviation)
Percentage change from baseline in 28-day seizure frequency at 3 months (day 91), 26 weeks, 52 week OLE (Mean Percent Change \& Standard Deviation)
Measured: Baseline through 52 week open label period
Summary of 28-day Seizure Frequency for Sum of Individual Seizures and Clusters Through 52-week OLE (Median Percent Change)
Percentage change from baseline in 28-day seizure frequency at 3 months (day 91), 26 weeks, 52 week OLE (Median Percent Change)
Measured: Baseline through 52-week open- label period

Secondary outcomes (4)

Summary of CGII-C
Clinician Global Impression of Change score as assessed by questionnaire. [ Time Frame: 78 Weeks ] CGII-C scale is qualitative values and not quantitative.
Measured: End of Week 4, End of Week 8, End of Week 17, End of Week 26, Week 44, Week 62, Week 78
Summary of CGII-P
Patient Global Impression of Change score as assessed by questionnaire. [ Time Frame: 78 Weeks ] CGII-P scale is qualitative values and not quantitative.
Measured: Patient Global Impression of Change score as assessed by questionnaire. [ Time Frame: 78 Weeks ]
Number of Participants With Responder Rate of Seizure Frequency
Responder Rate in Terms of 28-day Seizure Frequency Based on the Sum of Individual Seizures and Clusters
Measured: Month 3 and Week 26
Mean Percentage Change of Individual Seizure-free Days
Mean Percentage Change of Individual Seizure-free days per 28-day period (through 52-week OLE) period relative to baseline
Measured: Baseline, Day 91, Week 26, 52-week OLE through month 6, 52-week OLE Period

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

6 Nov 20154 Jan 2019

First posted9 Feb 2015 (estimated)
Study start6 Nov 2015
Primary completion16 Jan 2018
Study completion4 Jan 2019

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 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: Prevention
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 30 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02358538
Sponsor's protocol ID: 1042-900
Status last verified: Mar 2023
First submitted: 30 Jan 2015
Last updated: 21 Mar 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruiting
Clinical Trial of SEEG for Drug-resistant Epilepsy
Drug-Resistant Epilepsy
RecruitingPhase 3
Investigate Efficacy and Safety of Carisbamate as Adjunctive Treatment for Seizures Associated With LGS in Children and Adults
Seizures, Lennox Gastaut Syndrome
RecruitingPhase 3
Study Evaluating the Efficacy and Safety of RAP-219 in Adult Participants With Focal Seizures
Focal Seizure, Epilepsy
Active, not recruitingObservational study
Transforming Research and Clinical Knowledge in Traumatic Brain Injury Epileptogenesis Project (TRACK-TBI EPI)
Traumatic Brain Injury, Post-traumatic Epilepsy
RecruitingPhase 3
Study Evaluating the Efficacy and Safety of RAP-219 in Adult Participants With Focal Seizures FOCUS-1
Focal Seizure, Epilepsy

All Epilepsy trials

Study at a glance

From the registry record, last updated by the sponsor on 21 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multicenter, Open-Label Proof-of-Concept Trial of Ganaxolone in Children With PCDH19 Female Pediatric Epilepsy and Other Rare Genetic Epilepsies Followed by 52 Week Open-Label Treatment
ClinicalTrials.gov ID: NCT02358538
Acronym / sponsor ID: 1042-900
Conditions: Epilepsy
Keywords: PCDH19, ganaxolone, neurosteroid, CDKL5, LGS, CSWS
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 30 participants (actual)
Lead sponsor: Marinus PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: 6 Nov 2015 (actual)
Primary completion: 16 Jan 2018 (actual)
Study completion: 4 Jan 2019 (actual)
First posted: 9 Feb 2015 (estimated)
Results: Posted 7 Sep 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Prevention
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Ganaxolone	Experimental	Drug: GanaxoloneMaximum of 1800 mg/day or 63 mg/kg/day

Who may qualify

Ages: 2 to 18 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (7 listed)

Have parent or legal guardian available and willing to give written informed consent.
Male and female outpatients between 2 and 18 years of age years of age at time of consent.
Have any of the following epilepsy syndromes: PCDH19; CDKL5; Dravet Syndrome; Lennox Gastaut Syndrome (LGS); Continuous Spikes and Waves during Sleep (CSWS)
Have uncontrolled cluster seizures and/or non-clustered seizures.
Subjects should be on a stable regimen of anti-epileptic medication, and generally in good health.

Key exclusion criteria (7 listed)

Have had previous exposure to ganaxolone.
Known sensitivity or allergy to any component in the study drug, progesterone, or other related steroid compounds.
Exposure to any investigational drug or device < 90 days prior to screening, or plans to participate in another drug or device trial at any time during the study.
Concurrent use of vigabatrin, tiagabine, or ezogabine is not permitted.
Have any medical condition that, in the investigator's judgment, is considered to be clinically significant and could potentially affect subject safety or study outcome, including but not limited to: clinically significant cardiac, renal, pulmonary, gastrointestinal, hematologic or hepatic conditions; or a condition that affects the absorption, distribution, metabolism or excretion of drugs.

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
GanaxoloneAlso: CCD 1042oral suspension or capsules	Drug	Ganaxolone

Primary outcome

Summary of 28-day Seizure Frequency for Sum of Individual Seizures and Clusters for 52-week OLE Period (Mean Percent Change & Standard Deviation)
Time frame: Baseline through 52 week open label period
Percentage change from baseline in 28-day seizure frequency at 3 months (day 91), 26 weeks, 52 week OLE (Mean Percent Change \& Standard Deviation)
Summary of 28-day Seizure Frequency for Sum of Individual Seizures and Clusters Through 52-week OLE (Median Percent Change)
Time frame: Baseline through 52-week open- label period
Percentage change from baseline in 28-day seizure frequency at 3 months (day 91), 26 weeks, 52 week OLE (Median Percent Change)

4 secondary outcomes

Summary of CGII-C
Time frame: End of Week 4, End of Week 8, End of Week 17, End of Week 26, Week 44, Week 62, Week 78
Summary of CGII-P
Time frame: Patient Global Impression of Change score as assessed by questionnaire. [ Time Frame: 78 Weeks ]
Number of Participants With Responder Rate of Seizure Frequency
Time frame: Month 3 and Week 26
Mean Percentage Change of Individual Seizure-free Days
Time frame: Baseline, Day 91, Week 26, 52-week OLE through month 6, 52-week OLE Period

Results and safety

Results posted to the registry on 7 Sep 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
CDKL5	7	4
CSWS	2	0
Lennox-Gastaut	10	5
PCDH19	11	6

Primary outcome: Summary of 28-day Seizure Frequency for Sum of Individual Seizures and Clusters for 52-week OLE Period (Mean Percent Change & Standard Deviation)

Time frame: Baseline through 52 week open label period. Mean (Standard Deviation). Unit: percentage of change of frequency

Measure	CDKL5 n = 7	CSWS n = 2	Lennox- Gastaut n = 10	PCDH19 n = 11
Percent Change from baseline (at day 91)	-31.23 (41.438)	NA (NA)	122.10 (321.124)	52.83 (234.084)
Percent Change from baseline (at week 26)	-20.55 (60.588)	NA (NA)	125.38 (319.051)	46.36 (235.661)
Percent change from baseline (52 week OLE through month 6)	-54.41 (40.286)	NA (NA)	-38.74 (9.292)	-19.98 (63.644)
Percent change from baseline (52 week OLE period)	-49.20 (50.206)	NA (NA)	-37.75 (7.891)	-19.95 (63.571)

Population analysed: MITT Population

Primary outcome: Summary of 28-day Seizure Frequency for Sum of Individual Seizures and Clusters Through 52-week OLE (Median Percent Change)

Time frame: Baseline through 52-week open- label period. Median (Full Range). Unit: Median Percent Change in Frequency

Measure	CDKL5 n = 7	Lennox-Gastaut n = 10	PCDH19 n = 11	CSWS n = 2
Percent change from baseline (at Day 91)	-47.34 (-80.9 to 36.8)	-10.22 (-68.1 to 904.3)	-25.98 (-100.00 to 723.2)	NA (NA to NA)
Percent change from baseline (at week 26)	-37.70 (-85.3 to 99.9)	-9.19 (-71.2 to 904.3)	-24.59 (-100.00 to 723.2)	NA (NA to NA)
Percent change from baseline (at week 26) - with 6 duplicate diary entries removed	-44.4 (-85.3 to 99.9)	NA (NA to NA)	NA (NA to NA)	NA (NA to NA)
Percent change from baseline (52 week OLE through month 6)	-58.94 (-89.4 to -10.4)	-38.74 (-45.3 to -32.2)	-13.48 (-100.0 to 59.6)	NA (NA to NA)
Percent change from baseline (52 week OLE period)	-61.93 (-89.5 to 16.6)	-37.75 (-43.3 to -32.2)	-13.48 (-99.0 to 59.6)	NA (NA to NA)

Population analysed: MITT Population

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Combined 26-week open label period and 52-week open label extension period. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
CDKL5	1 of 7 (14.3%)	7 of 7 (100%)	0 of 7
CSWS	1 of 2 (50%)	1 of 2 (50%)	0 of 2
Lennox-Gastaut	2 of 10 (20%)	7 of 10 (70%)	0 of 10
PCDH19	3 of 11 (27.3%)	11 of 11 (100%)	0 of 11

Limitations and caveats (from the sponsor): CSWS cohort was not included in efficacy summaries as only 2 subjects were enrolled in cohort; however, cohort was included in the subject data listings. Overall number of participants affected is associated with all TEAEs and not \>-5%. Individual AEs are associated with \>-5%. One patient in the CDKL5 cohort had duplication of data on 6 days, which appeared to PI and sponsor to be erroneous. This datapoint is represented accordingly in outcome measure

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Related trials for Epilepsy

Not yet recruiting
Clinical Trial of SEEG for Drug-resistant Epilepsy
Drug-Resistant Epilepsy
RecruitingPhase 3
Investigate Efficacy and Safety of Carisbamate as Adjunctive Treatment for Seizures Associated With LGS in Children and Adults
Seizures, Lennox Gastaut Syndrome
RecruitingPhase 3
Study Evaluating the Efficacy and Safety of RAP-219 in Adult Participants With Focal Seizures
Focal Seizure, Epilepsy
Active, not recruitingObservational study
Transforming Research and Clinical Knowledge in Traumatic Brain Injury Epileptogenesis Project (TRACK-TBI EPI)
Traumatic Brain Injury, Post-traumatic Epilepsy
RecruitingPhase 3
Study Evaluating the Efficacy and Safety of RAP-219 in Adult Participants With Focal Seizures FOCUS-1
Focal Seizure, Epilepsy

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.

10 sites in 2 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 Epilepsy, run by Marinus Pharmaceuticals at 10 sites in 2 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 7 inclusion and 7 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 21 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States, Italy. 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 7 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 for Sum of Individual Seizures and Clusters for 52-week OLE Period (Mean Percent Change & Standard Deviation) (time frame: Baseline through 52 week open label period). The study lists 2 primary outcomes in all. 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 NCT02358538.

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 21 Mar 2023.