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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05323734




Registration number
NCT05323734
Ethics application status
Date submitted
21/03/2022
Date registered
12/04/2022

Titles & IDs
Public title
Adjunctive GNX Treatment Compared With Placebo in Children and Adults With TSC-related Epilepsy
Scientific title
A Phase 3, Double-blind, Randomized, Placebo-controlled Trial of Adjunctive Ganaxolone (GNX) Treatment in Children and Adults With Tuberous Sclerosis Complex (TSC)-Related Epilepsy (TrustTSC)
Secondary ID [1] 0 0
1042-TSC-3001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Tuberous Sclerosis Complex 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Neurological 0 0 0 0
Other neurological disorders
Neurological 0 0 0 0
Epilepsy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ganaxalone
Treatment: Drugs - Placebo

Experimental: Ganaxalone (GNX) - oral suspension, 3 times a day (TID)

Placebo comparator: Placebo matching GNX - oral suspension, TID


Treatment: Drugs: Ganaxalone
GNX will be administered

Treatment: Drugs: Placebo
Placebo will be administered
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Double-blind phase: Percent change from Baseline in 28-day seizure frequency during titration and maintenance period
Timepoint [1] 0 0
Baseline (Day 1) through Week 16
Secondary outcome [1] 0 0
Double-blind phase: Percent change from Baseline in 28-day seizure frequency during maintenance period
Timepoint [1] 0 0
Baseline (Day 1) and Day 29 to Week 16
Secondary outcome [2] 0 0
Double-blind phase: Number of participants who will be considered as treatment responders during titration and maintenance phase
Timepoint [2] 0 0
Up to 16 weeks
Secondary outcome [3] 0 0
Double-blind phase: Number of participants who will be considered as treatment responders during maintenance phase
Timepoint [3] 0 0
Day 29 to Week 16
Secondary outcome [4] 0 0
Double-blind phase: Number of Participants with Clinical Global Impression of Improvement (CGI-I) during titration and maintenance phase
Timepoint [4] 0 0
Up to 16 weeks
Secondary outcome [5] 0 0
Double-blind phase: Change from Baseline in Anxiety, Depression, and Mood Scale (ADAMS) during titration and maintenance phase
Timepoint [5] 0 0
Baseline (Day 1) through Week 16
Secondary outcome [6] 0 0
Double-blind phase: Change from Baseline in Short Form-36 (SF-36) during titration and maintenance phase
Timepoint [6] 0 0
Baseline (Day 1) through 16 weeks
Secondary outcome [7] 0 0
Double-blind phase: Change from Baseline in Pediatric Quality of Life Inventory - Family Impact Module (Peds-QL-FIM) during titration and maintenance phase
Timepoint [7] 0 0
Baseline (Day 1) through 16 weeks
Secondary outcome [8] 0 0
Double-blind phase: Change from Baseline in Epilepsy and Learning Disabilities Quality of Life (ELDQOL) Scale during titration and maintenance phase
Timepoint [8] 0 0
Baseline (Day 1) through 16 weeks
Secondary outcome [9] 0 0
Double-blind phase: Change from Baseline in the percentage of seizure-free day during titration and maintenance phase
Timepoint [9] 0 0
Baseline (Day 1) through 16 weeks
Secondary outcome [10] 0 0
Double-blind phase: Change from Baseline in Caregiver Global Impression of Change in Seizure Intensity/Duration (CGI-CSID) during titration and maintenance phase
Timepoint [10] 0 0
Baseline (Day 1) through 16 weeks
Secondary outcome [11] 0 0
Double-blind phase: Number of participants with a = 25% and = 75% reduction from Baseline during titration and maintenance phase
Timepoint [11] 0 0
Up to 16 weeks
Secondary outcome [12] 0 0
Double-blind phase: Number of participants with a = 25%, = 50%, and = 75% reduction from Baseline during maintenance phase
Timepoint [12] 0 0
Day 29 to Week 16
Secondary outcome [13] 0 0
Double-blind phase: Number of participants with Responder Analysis using = 0%, > 0% to < 25%, = 25% to < 50%, = 50% to < 75%, and = 75% to 100% during titration and maintenance phase
Timepoint [13] 0 0
Up to 16 weeks
Secondary outcome [14] 0 0
Double-blind phase: Percent change in 28-day frequency of all seizures during titration and maintenance phase
Timepoint [14] 0 0
Up to 16 weeks
Secondary outcome [15] 0 0
Double-blind phase: Change from Baseline in percentage of Seizure-Free Days during titration and maintenance phase
Timepoint [15] 0 0
Baseline (Day 1) and through 16 weeks
Secondary outcome [16] 0 0
Double-blind phase: Change from Baseline in longest Seizure-Free Interval during titration and maintenance phase
Timepoint [16] 0 0
Baseline (Day 1) through 16 weeks

Eligibility
Key inclusion criteria
1. Clinical or mutational diagnosis of TSC consistent with:

1. Molecular confirmation of a pathogenic mutation in TSC1 or TSC2. A pathogenic mutation is defined as a mutation that clearly prevents protein synthesis and/or inactivates the function of the TSC1 or TSC2 proteins (eg, nonsense mutation or frameshift mutations, large genomic deletions) or is a missense mutation whose effect on protein function has been established by functional assessment. The Principal investigator (PI) or designee must review the results of the genetic analysis and confirm that the causal relationship to the epilepsy syndrome is likely. OR
2. Clinical diagnosis of definite TSC which includes 2 major features or 1 major feature with = 2 minor features.
2. Male or female participants aged 1 through 65 years, inclusive. For Europe (EU), Middle East and North Africa (MENA), and Oceania (OC) Male or Female participants aged 2 through 65 years, inclusive.
3. Participant/parent(s) or LAR(s) willing to give written informed consent/assent, after being properly informed of the nature and risks of the study and prior to engaging in any study related procedures. If the participant is not qualified nor able to provide written informed consent based on age, developmental stage, intellectual capacity, or other factors, parent(s)/LAR(s) must provide consent for study participation, if appropriate.
4. Failure to control seizures despite appropriate trial of 2 or more Anti-seizure medication (ASMs) at therapeutic doses and for adequate duration of treatment per PI judgment.
5. Participants should be on a stable regimen of ASMs (including moderate or strong inducer or inhibitor ASM eg, carbamazepine, phenytoin, etc.) at therapeutic doses for = 28 days prior to the screening visit, and without a foreseeable change in dosing for the duration of the study. (Note: Minor dose adjustment to address tolerability and safety events may be allowed on case-by-case basis and it should be discussed with the study medical monitor.)
6. A history of at least 8 countable seizures per month in the 2 months prior to screening with no more than 1 seizure free week in each month. This includes seizures of any kind.
7. Have at least 8 primary endpoint seizures in the first 28 days following the screening visit.

The primary endpoint seizure types are defined as the following:
1. focal motor seizures without impairment of consciousness or awareness
2. focal seizures with impairment of consciousness or awareness with motor features
3. focal seizures evolving to bilateral, tonic-clonic seizures
4. generalized motor seizures including tonic-clonic, bilateral tonic, bilateral clonic, or atonic/drop seizures.

Seizures that do not count towards the primary endpoint include:
1. Focal or generalized nonmotor seizures (eg, absence seizures or focal nonmotor seizures with or without impairment of awareness)
2. Infantile or epileptic spasms
3. Myoclonic seizures.
8. Participants with surgically implanted vagal nerve stimulator (VNS) will be allowed to enter the study provided that all of the following conditions are met:

1. The VNS has been in place for = 6 months prior to the screening visit.
2. The settings must have remained constant for 3 months prior to the screening visit and are expected to remain constant throughout the study.
3. The battery is expected to last for the duration of the study.
9. Parent(s)/caregiver(s)/LAR(s) or the participant, as appropriate, is (are) willing and able to maintain an accurate and complete daily seizure eDiary for the duration of the study.
10. Willing and able to take IP (suspension) as directed with food (TID).
11. Women of childbearing potential (WOCBP) must be using a medically acceptable method of birth control and have a negative quantitative serum beta-human chorionic growth hormone (ß-HCG) test collected at the initial screening and Baseline visits.Childbearing potential is defined as a female who is biologically capable of becoming pregnant. A medically acceptable method of birth control includes intrauterine devices (that have been in place for at least 1 month prior to the screening visit), hormonal contraceptives (eg, combined oral contraceptives, patch, vaginal ring, injectables, and implants), and surgical sterilization (such as oophorectomy or tubal ligation. When used consistently and correctly, "double-barrier" methods of contraception can be used as an effective alternative to highly effective contraception methods. Contraceptive measures such as Plan B™, sold for emergency use after unprotected sex, are not acceptable methods for routine use.
12. Male participants must agree to use highly effective contraceptive methods during the study and for 30 days after the last dose of IP. Highly effective methods of contraception include surgical sterilization (such as a vasectomy) and adequate "double-barrier" methods.
Minimum age
1 Year
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Previous exposure to GNX.
2. Pregnant or breastfeeding.
3. Participants who have been taking felbamate for less than 1 year prior to screening.
4. Participants taking cannabidiol (CBD) preparations other than Epidiolex.
5. A positive result on plasma drug screen for CBD or tetrahydrocannabinol (THC) at Visit 1 (screening), with the exception of results that are fully explained by Epidiolex, which can be adjusted by the investigator in the event of any Adverse events (AEs).
6. Concurrent use of adrenocorticotropic hormone (ACTH), prednisone or other glucocorticoid is not permitted, nor use of the strong inducers of cytochrome P450 3A4 (CYP3A4), rifampin and St John's Wort. Participants on ACTH, prednisone, or other systemically (non-inhaled or topical) administered steroids should be off the product > 28 days prior to screening. Rifampin and St John's Wort must be discontinued at least 28 days before Visit 2, study drug initiation.

Note:
1. Use of concomitant intranasal or pro re nata (PRN) topical steroids for dermatologic reactions and allergic rhinitis are allowed during the study.
2. This exclusion criterion does not prohibit the use of approved ASMs.
7. Changes in any chronic medications within the 4 weeks prior to the screening visit. All chronic concomitant medications must be relatively stable in dose for at least 4 weeks prior to the screening visit unless otherwise noted. Small dose adjustment to manage tolerability and safety events is permitted and should be discussed with the study medical monitor.
8. Participants who have epilepsy surgery planned during the study or who have undergone surgery for epilepsy within the 6 months prior to screening.
9. An active central nervous system (CNS) infection, demyelinating disease, degenerative neurological disease, or CNS disease deemed progressive as evaluated by brain magnetic resonance imaging (MRI). This includes tumor growth which in the opinion of the investigator could affect primary endpoint seizure control.
10. Any disease or condition (medical or surgical; other than TSC) at the screening visit that might compromise the hematologic, cardiovascular (including any cardiac conduction defect), pulmonary, renal, gastrointestinal, or hepatic systems; or other conditions that might interfere with the absorption, distribution, metabolism, or excretion of the IP, or would place the participant at increased risk or interfere with the assessment of safety/efficacy. This may include any illness in the past 4 weeks which in the opinion of the investigator may affect seizure frequency.
11. Hepatic impairment sufficient to affect participant safety, or an aspartate aminotransferase (AST)/ serum glutamic oxaloacetic transaminase (SGOT) or alanine aminotransferase (ALT)/ serum glutamic pyruvic transaminase (SGPT) > 3 × the upper limit of normal (ULN) at screening or Baseline visits and confirmed by a repeat test.
12. Biliary impairment sufficient to affect participant safety, or total bilirubin levels > 1.5 × ULN at screening or Baseline visit and confirmed by a repeat test. In cases of Gilbert's Syndrome, resulting in stable levels of total bilirubin greater than ULN, the medical monitor can determine if a protocol exception can be made
13. Renal impairment sufficient to affect participant safety, or estimated glomerular filtration rate (eGFR) < 30 milliliter per minute (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. Cases of temporary renal insufficiency should be discussed with the medical monitor to determine the participant's study continuation.
14. Exposed to any other investigational drug or investigational device within 30 days or fewer than 5 half-lives prior to the screening visit. For therapies in which half-life cannot be readily established, the Sponsor's Medical Monitor should be consulted.
15. Unwillingness to avoid excessive alcohol use throughout the study.
16. Have active suicidal plan/intent, active suicidal thoughts or a suicide attempt in the past 6 months.
17. Known sensitivity or allergy to any component in the IP(s), progesterone, or other related steroid compounds.
18. Participants deprived of their liberty by a judicial or administrative decision, or for psychiatric treatment, or participants admitted to a health or social services facility for purposes other than research.
19. Participants receiving traditional Chinese medicine therapies within the prior 28 days of the screening.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/04/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
14/10/2024
Sample size
Target
Accrual to date
Final
128
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [2] 0 0
Austin Health - Heidelberg
Recruitment hospital [3] 0 0
Alfred Health - Melbourne
Recruitment hospital [4] 0 0
Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
4029 - Herston
Recruitment postcode(s) [2] 0 0
3084 - Heidelberg
Recruitment postcode(s) [3] 0 0
3004 - Melbourne
Recruitment postcode(s) [4] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Delaware
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
Tennessee
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
United States of America
State/province [15] 0 0
Utah
Country [16] 0 0
United States of America
State/province [16] 0 0
Washington
Country [17] 0 0
Canada
State/province [17] 0 0
Montreal
Country [18] 0 0
Canada
State/province [18] 0 0
Montréal
Country [19] 0 0
Canada
State/province [19] 0 0
Toronto
Country [20] 0 0
Canada
State/province [20] 0 0
Vancouver
Country [21] 0 0
China
State/province [21] 0 0
Jilin
Country [22] 0 0
China
State/province [22] 0 0
Nanchang City
Country [23] 0 0
China
State/province [23] 0 0
Xicheng District
Country [24] 0 0
China
State/province [24] 0 0
Yunyan District
Country [25] 0 0
China
State/province [25] 0 0
Beijing
Country [26] 0 0
China
State/province [26] 0 0
Chengdu
Country [27] 0 0
France
State/province [27] 0 0
Bron
Country [28] 0 0
France
State/province [28] 0 0
Rennes
Country [29] 0 0
France
State/province [29] 0 0
Strasbourg
Country [30] 0 0
Germany
State/province [30] 0 0
Bielefeld
Country [31] 0 0
Germany
State/province [31] 0 0
Bonn
Country [32] 0 0
Germany
State/province [32] 0 0
Frankfurt
Country [33] 0 0
Germany
State/province [33] 0 0
Freiburg
Country [34] 0 0
Germany
State/province [34] 0 0
Herdecke
Country [35] 0 0
Germany
State/province [35] 0 0
Radeberg
Country [36] 0 0
Israel
State/province [36] 0 0
Petah Tikva
Country [37] 0 0
Israel
State/province [37] 0 0
Tel Hashomer
Country [38] 0 0
Italy
State/province [38] 0 0
Bari
Country [39] 0 0
Italy
State/province [39] 0 0
Genova
Country [40] 0 0
Italy
State/province [40] 0 0
Rome
Country [41] 0 0
Spain
State/province [41] 0 0
Barcelona
Country [42] 0 0
Spain
State/province [42] 0 0
Madrid
Country [43] 0 0
Spain
State/province [43] 0 0
Málaga
Country [44] 0 0
Spain
State/province [44] 0 0
Valencia
Country [45] 0 0
United Kingdom
State/province [45] 0 0
Bristol
Country [46] 0 0
United Kingdom
State/province [46] 0 0
Oxford
Country [47] 0 0
United Kingdom
State/province [47] 0 0
Salford
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Marinus Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05323734