Trial Outcomes & Findings for Adjunctive GNX Treatment Compared With Placebo in Children and Adults With TSC-related Epilepsy (NCT NCT05323734)

Last Updated: 2025-07-11

Results Overview

Primary seizures include atonic/drop, bilateral clonic, bilateral tonic, focal motor with altered awareness, focal motor with intact awareness, focal to bilateral tonic-clonic seizures, focal with hypotonia impaired awareness, and generalized tonic-clonic. Seizure frequency was calculated as the total number of seizures divided by the number of days with seizure data in the period, multiplied by 28. Percent change from Baseline in 28-day seizure frequency was calculated as follows for each participant: post-baseline 28-day seizure frequency minus baseline 28-day seizure frequency whole divided by baseline 28-day seizure frequency and multiplied by 100.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

129 participants

Primary outcome timeframe

Baseline (Day 1), Day 28

Results posted on

2025-07-11

Participant Flow

This was a Phase 3, global, double-blind, randomized, placebo-controlled study of adjunctive Ganaxolone treatment in children and adults with TSC-related epilepsy.

A total of 129 participants were enrolled in the study.

Participant milestones

Participant milestones
Measure	Ganaxolone Participants were randomized to receive an oral suspension of Ganaxolone based on their body weight. Ganaxolone 63 milligrams/kilograms/day (mg/kg/day) was administered orally three times a day (TID) to participants weighing 28 kg or less. Ganaxolone 1800 mg/day TID was administered orally to participants weighing more than 28 kg.	Placebo Participants were administered with matching placebo as oral suspension TID based on the body weight.
Overall Study STARTED	64	65
Overall Study COMPLETED	55	60
Overall Study NOT COMPLETED	9	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Ganaxolone Participants were randomized to receive an oral suspension of Ganaxolone based on their body weight. Ganaxolone 63 milligrams/kilograms/day (mg/kg/day) was administered orally three times a day (TID) to participants weighing 28 kg or less. Ganaxolone 1800 mg/day TID was administered orally to participants weighing more than 28 kg.	Placebo Participants were administered with matching placebo as oral suspension TID based on the body weight.
Overall Study Adverse Event	5	2
Overall Study Physician Decision	1	0
Overall Study Lack of Efficacy	1	2
Overall Study Withdrawal by Subject	2	0
Overall Study Participant Withdrawn Due	0	1

Baseline Characteristics

Adjunctive GNX Treatment Compared With Placebo in Children and Adults With TSC-related Epilepsy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ganaxolone n=64 Participants Participants were randomized to receive an oral suspension of Ganaxolone based on their body weight. Ganaxolone 63 milligrams/kilograms/day (mg/kg/day) was administered orally three times a day (TID) to participants weighing 28 kg or less. Ganaxolone 1800 mg/day TID was administered orally to participants weighing more than 28 kg.	Matching Placebo n=65 Participants Participants were administered with matching placebo as oral suspension TID based on the body weight.	Total n=129 Participants Total of all reporting groups
Age, Continuous	14.7 Years STANDARD_DEVIATION 11.0 • n=5 Participants	16.1 Years STANDARD_DEVIATION 11.2 • n=7 Participants	15.4 Years STANDARD_DEVIATION 11.1 • n=5 Participants
Sex: Female, Male Female	36 Participants n=5 Participants	29 Participants n=7 Participants	65 Participants n=5 Participants
Sex: Female, Male Male	28 Participants n=5 Participants	36 Participants n=7 Participants	64 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	52 Participants n=5 Participants	55 Participants n=7 Participants	107 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	12 Participants n=5 Participants	11 Participants n=7 Participants	23 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants	2 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) White	41 Participants n=5 Participants	48 Participants n=7 Participants	89 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1), Day 28

Population: Intent-to-treat (ITT) Set comprises of randomized participants who dosed and had at least one post-baseline efficacy assessment.

Outcome measures

Outcome measures
Measure	Ganaxolone n=64 Participants Participants were randomized to receive oral suspension of Ganaxolone 63 milligrams/kilograms/day (mg/kg/day) for those weighing 28 kg or less and 1800 mg/day for those weighing more than 28 kg three times a day.	Matching Placebo n=65 Participants Participants were administered with matching placebo as oral suspension 3 times a day.
Percent Change From Baseline in 28-day Seizure Frequency for Primary Seizure Type During Double Blind Period	-7.50 Percent change Standard Deviation 60.430	13.57 Percent change Standard Deviation 77.374

SECONDARY outcome

Timeframe: Up to 16 weeks

Population: ITT Set.

Treatment responders are defined as those participants with ≥ 50% reduction from Baseline in primary seizure type frequency during the given period.

Outcome measures

Outcome measures
Measure	Ganaxolone n=64 Participants Participants were randomized to receive oral suspension of Ganaxolone 63 milligrams/kilograms/day (mg/kg/day) for those weighing 28 kg or less and 1800 mg/day for those weighing more than 28 kg three times a day.	Matching Placebo n=65 Participants Participants were administered with matching placebo as oral suspension 3 times a day.
Number of Participants Who Were Considered as Treatment Responders During Double Blind Period	12 Participants	8 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) through 16 weeks

Population: ITT Set. Only those participants who responded to CGI-I scale has been presented.

The CGI-I is a 7-point Likert scale that the parent(s)/caregiver(s)/ legally authorized representative (LAR) and clinician uses to rate the change in overall seizure control, behavior, safety, and tolerability after initiation of the IP relative to baseline (prior to treatment with the IP). The participant was rated as follows: 1 - very much improved, 2 - much improved, 3 - minimally improved, 4 - no change, 5 - minimally worse, 6 - much worse, and 7 - very much worse. Higher scores indicated worse condition. Number of responders to each score on the scale has been presented.

Outcome measures

Outcome measures
Measure	Ganaxolone n=58 Participants Participants were randomized to receive oral suspension of Ganaxolone 63 milligrams/kilograms/day (mg/kg/day) for those weighing 28 kg or less and 1800 mg/day for those weighing more than 28 kg three times a day.	Matching Placebo n=58 Participants Participants were administered with matching placebo as oral suspension 3 times a day.
Number of Responders to Clinical Global Impression of Improvement (CGI-I) Scale as Assessed by Parent/Caregiver Very Much Improved	5 Participants	8 Participants
Number of Responders to Clinical Global Impression of Improvement (CGI-I) Scale as Assessed by Parent/Caregiver Much Improved	16 Participants	15 Participants
Number of Responders to Clinical Global Impression of Improvement (CGI-I) Scale as Assessed by Parent/Caregiver Minimally Improved	14 Participants	12 Participants
Number of Responders to Clinical Global Impression of Improvement (CGI-I) Scale as Assessed by Parent/Caregiver No Change	19 Participants	19 Participants
Number of Responders to Clinical Global Impression of Improvement (CGI-I) Scale as Assessed by Parent/Caregiver Minimally Worse	2 Participants	4 Participants
Number of Responders to Clinical Global Impression of Improvement (CGI-I) Scale as Assessed by Parent/Caregiver Much Worse	2 Participants	0 Participants
Number of Responders to Clinical Global Impression of Improvement (CGI-I) Scale as Assessed by Parent/Caregiver Very Much Worse	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) through 16 weeks

Population: ITT Set. Only those participants who responded to CGI-I scale has been presented.

The CGI-I is a 7-point Likert scale that the parent(s)/caregiver(s)/ LAR and clinician uses to rate the change in overall seizure control, behavior, safety, and tolerability after initiation of the IP relative to baseline (prior to treatment with the IP). The participant was rated as follows: 1 - very much improved, 2 - much improved, 3 - minimally improved, 4 - no change, 5 - minimally worse, 6 - much worse, and 7 - very much worse. Number of responders to each score on the scale has been presented.

Outcome measures

Outcome measures
Measure	Ganaxolone n=51 Participants Participants were randomized to receive oral suspension of Ganaxolone 63 milligrams/kilograms/day (mg/kg/day) for those weighing 28 kg or less and 1800 mg/day for those weighing more than 28 kg three times a day.	Matching Placebo n=53 Participants Participants were administered with matching placebo as oral suspension 3 times a day.
Number of Responders to Clinical Global Impression of Improvement (CGI-I) Scale as Assessed by Clinician Very Much Improved	0 Participants	3 Participants
Number of Responders to Clinical Global Impression of Improvement (CGI-I) Scale as Assessed by Clinician Much Improved	14 Participants	13 Participants
Number of Responders to Clinical Global Impression of Improvement (CGI-I) Scale as Assessed by Clinician Minimally Improved	12 Participants	11 Participants
Number of Responders to Clinical Global Impression of Improvement (CGI-I) Scale as Assessed by Clinician No Change	22 Participants	25 Participants
Number of Responders to Clinical Global Impression of Improvement (CGI-I) Scale as Assessed by Clinician Minimally Worse	2 Participants	1 Participants
Number of Responders to Clinical Global Impression of Improvement (CGI-I) Scale as Assessed by Clinician Much Worse	1 Participants	0 Participants
Number of Responders to Clinical Global Impression of Improvement (CGI-I) Scale as Assessed by Clinician Very Much Worse	0 Participants	0 Participants

Adverse Events

Ganaxolone

Serious events: 5 serious events

Other events: 58 other events

Deaths: 0 deaths

Matching Placebo

Serious events: 6 serious events

Other events: 49 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ganaxolone n=64 participants at risk Participants were randomized to receive oral suspension of Ganaxolone 63 milligrams/kilograms/day (mg/kg/day) for those weighing 28 kg or less and 1800 mg/day for those weighing more than 28 kg three times a day.	Matching Placebo n=65 participants at risk Participants were administered with matching placebo as oral suspension 3 times a day.
Infections and infestations Erysipelas	1.6% 1/64 • Up to 16 Weeks Serious treatment emergent adverse events and treatment emergent adverse events were collected in Safety Analysis Set which comprises of all randomized participants who received at least 1 dose of the IP.	0.00% 0/65 • Up to 16 Weeks Serious treatment emergent adverse events and treatment emergent adverse events were collected in Safety Analysis Set which comprises of all randomized participants who received at least 1 dose of the IP.
Infections and infestations Influenza	1.6% 1/64 • Up to 16 Weeks Serious treatment emergent adverse events and treatment emergent adverse events were collected in Safety Analysis Set which comprises of all randomized participants who received at least 1 dose of the IP.	1.5% 1/65 • Up to 16 Weeks Serious treatment emergent adverse events and treatment emergent adverse events were collected in Safety Analysis Set which comprises of all randomized participants who received at least 1 dose of the IP.
Infections and infestations Pneumonia	1.6% 1/64 • Up to 16 Weeks Serious treatment emergent adverse events and treatment emergent adverse events were collected in Safety Analysis Set which comprises of all randomized participants who received at least 1 dose of the IP.	1.5% 1/65 • Up to 16 Weeks Serious treatment emergent adverse events and treatment emergent adverse events were collected in Safety Analysis Set which comprises of all randomized participants who received at least 1 dose of the IP.
Infections and infestations Pneumonia Aspiration	1.6% 1/64 • Up to 16 Weeks Serious treatment emergent adverse events and treatment emergent adverse events were collected in Safety Analysis Set which comprises of all randomized participants who received at least 1 dose of the IP.	1.5% 1/65 • Up to 16 Weeks Serious treatment emergent adverse events and treatment emergent adverse events were collected in Safety Analysis Set which comprises of all randomized participants who received at least 1 dose of the IP.
Infections and infestations Cellulitis	0.00% 0/64 • Up to 16 Weeks Serious treatment emergent adverse events and treatment emergent adverse events were collected in Safety Analysis Set which comprises of all randomized participants who received at least 1 dose of the IP.	1.5% 1/65 • Up to 16 Weeks Serious treatment emergent adverse events and treatment emergent adverse events were collected in Safety Analysis Set which comprises of all randomized participants who received at least 1 dose of the IP.
Nervous system disorders Seizure	1.6% 1/64 • Up to 16 Weeks Serious treatment emergent adverse events and treatment emergent adverse events were collected in Safety Analysis Set which comprises of all randomized participants who received at least 1 dose of the IP.	1.5% 1/65 • Up to 16 Weeks Serious treatment emergent adverse events and treatment emergent adverse events were collected in Safety Analysis Set which comprises of all randomized participants who received at least 1 dose of the IP.
Injury, poisoning and procedural complications Craniocerebral Injury	0.00% 0/64 • Up to 16 Weeks Serious treatment emergent adverse events and treatment emergent adverse events were collected in Safety Analysis Set which comprises of all randomized participants who received at least 1 dose of the IP.	1.5% 1/65 • Up to 16 Weeks Serious treatment emergent adverse events and treatment emergent adverse events were collected in Safety Analysis Set which comprises of all randomized participants who received at least 1 dose of the IP.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	0.00% 0/64 • Up to 16 Weeks Serious treatment emergent adverse events and treatment emergent adverse events were collected in Safety Analysis Set which comprises of all randomized participants who received at least 1 dose of the IP.	1.5% 1/65 • Up to 16 Weeks Serious treatment emergent adverse events and treatment emergent adverse events were collected in Safety Analysis Set which comprises of all randomized participants who received at least 1 dose of the IP.

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

Restriction type: LTE60