Trial Outcomes & Findings for Adjunctive Ganaxolone Treatment (Part A) in TSC Followed by Long-term Treatment (Part B) (NCT NCT04285346)

Last Updated: 2023-04-04

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

23 participants

Primary outcome timeframe

Baseline and Up to Week 12

Results posted on

2023-04-04

Participant Flow

This was an open label proof of concept study of adjunctive Ganaxolone treatment in participants with a confirmed clinical diagnosis of Tuberous Sclerosis Complex (TSC). The trial consisted of two parts: 12-Week Treatment period and an open label extension period.

A total of 23 participants were enrolled in the study.

Participant milestones

Participant milestones
Measure	Treatment Period: Ganaxolone Participants \>28 kilograms (kg) were administered with Ganaxolone 1800 milligrams per day (mg/day). Following the Treatment period, participants with a seizure reduction of \>=35 percent compared to the Baseline period and who did not have any other contraindications continued to be treated with Ganaxolone in the Open label period.	Open Label: Ganaxolone Following the Treatment period, participants with a seizure reduction of \>=35 percent compared to the Baseline period and who did not have any other contraindications continued to be treated with Ganaxolone in the Open label period.
Treatment Period (Up to 12 Weeks) STARTED	23	0
Treatment Period (Up to 12 Weeks) COMPLETED	17	0
Treatment Period (Up to 12 Weeks) NOT COMPLETED	6	0
Open Label Period (Week 12 to 38) STARTED	0	9
Open Label Period (Week 12 to 38) COMPLETED	0	9
Open Label Period (Week 12 to 38) NOT COMPLETED	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment Period: Ganaxolone Participants \>28 kilograms (kg) were administered with Ganaxolone 1800 milligrams per day (mg/day). Following the Treatment period, participants with a seizure reduction of \>=35 percent compared to the Baseline period and who did not have any other contraindications continued to be treated with Ganaxolone in the Open label period.	Open Label: Ganaxolone Following the Treatment period, participants with a seizure reduction of \>=35 percent compared to the Baseline period and who did not have any other contraindications continued to be treated with Ganaxolone in the Open label period.
Treatment Period (Up to 12 Weeks) Adverse Event	4	0
Treatment Period (Up to 12 Weeks) Lack of Efficacy	1	0
Treatment Period (Up to 12 Weeks) Withdrawal by Subject	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment Period: Ganaxolone n=23 Participants Participants \>28 kg were administered with Ganaxolone 1800 milligrams per day (mg/day). Following the Treatment period, participants with a seizure reduction of \>=35 percent compared to the Baseline period and who did not have any other contraindications continued to be treated with Ganaxolone in the Open label extension period.
Age, Continuous	13.7 Years STANDARD_DEVIATION 8.86 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian	3 Participants n=5 Participants
Race/Ethnicity, Customized White	17 Participants n=5 Participants
Race/Ethnicity, Customized Declined to answer	1 Participants n=5 Participants
Race/Ethnicity, Customized Other-Unspecified	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Up to Week 12

Population: Intention to Treat (ITT) Population comprised of all participants who received at least one dose of Ganaxolone and have at least one post-Baseline efficacy assessment.

Outcome measures

Outcome measures
Measure	Treatment Period: Ganaxolone n=23 Participants Participants \>28 kilograms (kg) were administered with Ganaxolone 1800 milligrams per day (mg/day). Following the Treatment period, participants with a seizure reduction of \>=35 percent compared to the Baseline period and who did not have any other contraindications continued to be treated with Ganaxolone in the Open label period.
Percent Change From Baseline in 28-day Seizure Frequency Through the End of 12-Week Treatment Period	-16.61 Percent change Interval -56.4 to 14.86

SECONDARY outcome

Timeframe: Baseline and up to 12 Weeks

Population: ITT Population.

Outcome measures

Outcome measures
Measure	Treatment Period: Ganaxolone n=23 Participants Participants \>28 kilograms (kg) were administered with Ganaxolone 1800 milligrams per day (mg/day). Following the Treatment period, participants with a seizure reduction of \>=35 percent compared to the Baseline period and who did not have any other contraindications continued to be treated with Ganaxolone in the Open label period.
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	30.4 Percentage of participants

Adverse Events

Treatment Period: Ganaxolone

Serious events: 3 serious events

Other events: 20 other events

Deaths: 0 deaths

Open Label: Ganaxolone

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment Period: Ganaxolone n=23 participants at risk Participants \>28 kilograms (kg) were administered with Ganaxolone 1800 milligrams per day (mg/day). Following the Treatment period, participants with a seizure reduction of \>=35 percent compared to the Baseline period and who did not have any other contraindications continued to be treated with Ganaxolone in the Open label period.	Open Label: Ganaxolone n=9 participants at risk Following the Treatment period, participants with a seizure reduction of \>=35 percent compared to the Baseline period and who did not have any other contraindications continued to be treated with Ganaxolone in the Open label extension period.
Nervous system disorders Seizure	4.3% 1/23 • Number of events 1 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	0.00% 0/9 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
Respiratory, thoracic and mediastinal disorders Aspiration	4.3% 1/23 • Number of events 1 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	0.00% 0/9 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
Skin and subcutaneous tissue disorders Angioedema	4.3% 1/23 • Number of events 1 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	0.00% 0/9 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
Nervous system disorders Thalamic infarction	0.00% 0/23 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	11.1% 1/9 • Number of events 1 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.

Other adverse events

Additional Information

Marinus Clinical Trials Submission Manager

Marinus Pharmaceuticals, Inc.

Phone: 484-801-4670

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Treatment Period: Ganaxolone n=23 participants at risk Participants \>28 kilograms (kg) were administered with Ganaxolone 1800 milligrams per day (mg/day). Following the Treatment period, participants with a seizure reduction of \>=35 percent compared to the Baseline period and who did not have any other contraindications continued to be treated with Ganaxolone in the Open label period.	Open Label: Ganaxolone n=9 participants at risk Following the Treatment period, participants with a seizure reduction of \>=35 percent compared to the Baseline period and who did not have any other contraindications continued to be treated with Ganaxolone in the Open label extension period.
Nervous system disorders Somnolence	43.5% 10/23 • Number of events 13 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	0.00% 0/9 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
Nervous system disorders Sedation	13.0% 3/23 • Number of events 3 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	0.00% 0/9 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
Nervous system disorders Dizziness	8.7% 2/23 • Number of events 2 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	0.00% 0/9 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
Nervous system disorders Seizure	4.3% 1/23 • Number of events 1 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	0.00% 0/9 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
Nervous system disorders Ataxia	4.3% 1/23 • Number of events 1 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	0.00% 0/9 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
Nervous system disorders Balance disorder	4.3% 1/23 • Number of events 1 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	0.00% 0/9 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
Nervous system disorders Coordination abnormal	4.3% 1/23 • Number of events 1 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	0.00% 0/9 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
Nervous system disorders Hydrocephalus	4.3% 1/23 • Number of events 1 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	0.00% 0/9 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
Nervous system disorders Insomnia	4.3% 1/23 • Number of events 1 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	0.00% 0/9 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
Nervous system disorders Lethargy	4.3% 1/23 • Number of events 1 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	0.00% 0/9 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
Nervous system disorders Tremor	0.00% 0/23 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	11.1% 1/9 • Number of events 1 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
General disorders Fatigue	13.0% 3/23 • Number of events 3 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	0.00% 0/9 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
General disorders Asthenia	8.7% 2/23 • Number of events 3 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	0.00% 0/9 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
General disorders Gait disturbance	4.3% 1/23 • Number of events 1 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	0.00% 0/9 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
Infections and infestations Cellulitis	4.3% 1/23 • Number of events 1 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	0.00% 0/9 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
Infections and infestations Ear infection	4.3% 1/23 • Number of events 1 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	0.00% 0/9 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
Infections and infestations Gastroenteritis viral	4.3% 1/23 • Number of events 1 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	0.00% 0/9 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
Infections and infestations Viral infection	4.3% 1/23 • Number of events 1 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	0.00% 0/9 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
Gastrointestinal disorders Diarrhoea	4.3% 1/23 • Number of events 1 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	0.00% 0/9 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
Gastrointestinal disorders Gastrointestinal disorder	4.3% 1/23 • Number of events 1 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	0.00% 0/9 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
Gastrointestinal disorders Lip dry	4.3% 1/23 • Number of events 1 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	0.00% 0/9 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
Gastrointestinal disorders Duodenal ulcer	0.00% 0/23 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	11.1% 1/9 • Number of events 1 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
Injury, poisoning and procedural complications Burns second degree	4.3% 1/23 • Number of events 1 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	0.00% 0/9 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
Injury, poisoning and procedural complications Contusion	4.3% 1/23 • Number of events 1 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	0.00% 0/9 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
Injury, poisoning and procedural complications Skin wound	4.3% 1/23 • Number of events 1 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	0.00% 0/9 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
Injury, poisoning and procedural complications Tooth fracture	4.3% 1/23 • Number of events 1 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	0.00% 0/9 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
Injury, poisoning and procedural complications Skin abrasion	0.00% 0/23 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	11.1% 1/9 • Number of events 1 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
Injury, poisoning and procedural complications Tibia fracture	0.00% 0/23 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	11.1% 1/9 • Number of events 1 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
Metabolism and nutrition disorders Hyponatraemia	8.7% 2/23 • Number of events 2 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	0.00% 0/9 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
Metabolism and nutrition disorders Decreased appetite	4.3% 1/23 • Number of events 1 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	0.00% 0/9 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
Skin and subcutaneous tissue disorders Pruritus	4.3% 1/23 • Number of events 1 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	0.00% 0/9 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
Skin and subcutaneous tissue disorders Rash	4.3% 1/23 • Number of events 1 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	0.00% 0/9 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
Psychiatric disorders Abnormal behaviour	4.3% 1/23 • Number of events 1 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	0.00% 0/9 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
Psychiatric disorders Aggression	4.3% 1/23 • Number of events 1 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	0.00% 0/9 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	4.3% 1/23 • Number of events 2 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	0.00% 0/9 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
Respiratory, thoracic and mediastinal disorders Sneezing	4.3% 1/23 • Number of events 1 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	0.00% 0/9 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
Eye disorders Diplopia	4.3% 1/23 • Number of events 1 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	0.00% 0/9 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.
Investigations Immunosuppressant drug level increased	4.3% 1/23 • Number of events 1 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.	0.00% 0/9 • Up to Week 12 in Treatment period and From Week 12 to Week 38 in Open label period. Safety population comprised of all participants who received at least one dose of Ganaxolone.