A Phase 3, Open-label Study of Adjunctive Ganaxolone (GNX) Treatment in Children and Adults with Tuberous Sclerosis Complex (TSC)-related Epilepsy (TrustTSC OLE)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Marinus Pharmaceuticals Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

2 Oct 2023 → 25 Nov 2024

Decision date (initial)

2023-07-06

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Marinus Pharmaceutical, Inc

External identifiers

EU CT number

2022-503067-15-00

ClinicalTrials.gov

NCT05604170

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety

To assess the long -term safety and tolerability of GNX as adjunctive therapy for seizures associate with TSC in children and adults.

Secondary objectives 5

1. For the first year, to determine the percentage of change from baseline in 28day seizure frequency during open-label treatment.
2. For the first year, to assess the change in frequency of countable focal seizures frequency from baseline during open-label treatment.
3. For the first year, to assess changes in mood, behavior, and quality of life using SF-36
4. To assess overall clinical outcome using CGI-I scores by the clinician and the parent(s)/caregiver(s)/LAR(s).
5. To evaluate the changes in seizure intensity and duration using the CGI-CSID.

Conditions and MedDRA coding

Tuberous Sclerosis Complex (TSC) related epilepsy

Study design 1 period

Regulatory references

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Completion of Study 1042-TSC-3001 or participants who continue to meet study requirements in Study 1042-TSC-2001.
2. Participant/parent(s)/LAR(s) willing and able 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 or able to provide written informed consent based on age, developmental stage, intellectual capacity, or other factors, parent(s)/LAR(s) must provide assent for study participation, if appropriate.
3. Parents/caregivers is (are) willing and able to maintain an accurate and complete daily seizure diary for the duration of the study.
4. Willing and able to take IP (suspension) as directed with food 3 times a day (tid).
5. WOCBP must be using a medically acceptable method of birth control and have a negative quantitative serum β-human chorionic growth hormone (β-HCG) test collected at the initial visit. Childbearing potential is defined as a female who is biologically capable of becoming pregnant. Medically acceptable methods of birth control include 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 BTM, sold for emergency use after unprotected sex, are not acceptable methods for routine use.
6. 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.

Exclusion criteria 8

1. Pregnant or breastfeeding.
2. An active central nervous system (CNS) infection, demyelinating disease, or degenerative neurological disease.
3. History of psychogenic nonepileptic seizures.
4. Any disease or condition (other than TSC) at the initial visit that could 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.
5. Unwillingness to avoid excessive alcohol use or cannabis use throughout the study.
6. Have active suicidal plan/intent or have had active suicidal thoughts in the past 6 months or a suicide attempt in the past 6 months.
7. Known sensitivity or allergy to any component in the IP(s), progesterone, or other related steroid compounds.
8. Exposed to any other investigational drug (except for GNX in Study 1042-TSC-2001 or Study 1042-TSC-3001) or investigational device within 30 days or fewer than 5 half-lives prior to Visit 1 (first visit of the OLE). For therapies in which half-life cannot be readily established, the Sponsor’s medical monitor should be consulted.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 6

1. Incidence and severity of AEs, SAEs and withdrawals and dose-reductions due to AEs.
2. Vital sign measurements including blood pressure, heart rate, respiratory rate, body temperature, height, and body weight.
3. Physical, neurological, and developmental examination.
4. 12-lead ECG.
5. Clinical laboratory tests.
6. C-SSRS.

Secondary endpoints 7

1. Percentage change from baseline in 28-day seizure frequency during open-label treatment. (first year only)
2. Percentage change from baseline in 28-day seizure frequency during the long-term treatment. (first year only)
3. Number (%) of participants considered treatment responders. (first year only)
4. CGI-I at the last scheduled study visit.
5. Change from baseline in the quality-of-life scale SF-36. (first year only)
6. Change from baseline in the percentage of seizure-free days during treatment, based on seizure type. (first year only)
7. Change from baseline of CGI-CSID.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Marinus Pharmaceuticals Inc.

Sponsor organisation

Marinus Pharmaceuticals Inc.

Address

5 Radnor Corporate Center Suite 500

City

Wayne

Postcode

19087-4535

Country

United States

Scientific contact point

Organisation

Marinus Pharmaceuticals Inc.

Contact name

Senior Manager, Regulatory Affairs

Public contact point

Organisation

Marinus Pharmaceuticals Inc.

Contact name

Senior Manager, Regulatory Affairs

Third parties 13

Locations

5 EU/EEA countries · 25 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Urgent safety measures 1 · Art. 54 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications