Open-label extesnion study of soticlestat in Dravet and Lennox-Gastaut Syndromes

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Takeda Development Center Americas Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

5 Apr 2022 → 24 Sep 2025

Decision date (initial)

2024-02-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Takeda Development Center Americas, Inc.

External identifiers

EU CT number

2022-502802-34-00

EudraCT number

2021-002482-17

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Others, Efficacy

To asses the long-term safety and tolerability of soticlestat when administered as adjunctive therapy to SOC (eg ASMs, vagus nerve stimulation, ketogenic diet, modified Atkins diet) in subjects with DS or LGS.

Secondary objectives 5

1. To assess the effect of soticlestat on seizure frequency (convulsive seizures for the DS cohort, MMD seizures for the LGS cohort, and total seizure count for each cohort).
2. To assess the effect of soticlestat on the Clinical Global Impression of Improvement (CGI-I) (clinician) and Caregiver Global Impression of Improvement (Care GI-I).
3. To assess the effect of soticlestat on CGI-I Seizure Intensity and Duration.
4. To assess the effect of soticlestat on the CGI-I Nonseizure Symptoms completed by clinician with input from the caregiver.
5. To assess the effect on Quality of Life Inventory-Disability (QI-Disability).

Conditions and MedDRA coding

Dravet and Lennox-Gastaut Syndromes

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002572-PIP02-19

Plan to share IPD

Yes

IPD plan description

Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 01. Subject must have: been previously enrolled in a phase 3 soticlestat clinical study; received at least 12 weeks of treatment (combined Titration and Maintenance Periods) with the study drug in the antecedent study and not have a serious or severe AE that, in the investigator’s or sponsor’s opinion, was related to the study drug and would make it unsafe for the patient to continue receiving the study drug.
2. 02. In the opinion of the investigator, the subject has the potential to benefit from the administration of soticlestat.
3. "03. In the opinion of the investigator, the subject and/or the subject’s parent or legal guardian or caregiver is capable of understanding and complying with protocol requirements including completion of appropriate assessments, maintaining an accurate and complete daily seizure diary, and taking study drug for the duration of the study. If the subject is living in a residential facility, a minimally possible number of staff member(s) at the facility who are the subject’s primary caretaker(s) may be identified as caregivers who (per investigator’s judgment) are capable of complying with protocol requirements as indicated above."
4. "04. The subject or the subject’s parent or legal guardian is willing and able to read, understand, and sign and date an informed consent form (ICF), assent form (if applicable), and any required privacy authorization before the initiation of any study procedures. In the opinion of the investigator, the subject and/or the subject’s parent or legal guardian or caregiver is capable of understanding and complying with protocol requirements including completion of appropriate assessments, maintaining an accurate and complete daily seizure diary, and taking study drug for the duration of the study. If the subject is living in a residential facility, a minimally possible number of staff member(s) at the facility who are the subject’s primary caretaker(s) may be identified as caregivers who (per investigator’s judgment) are capable of complying with protocol requirements as indicated above."
5. "05. Female subjects of childbearing potential (defined as first menarche) must have a negative pregnancy test and agree to use an effective (not applicable for Germany) or highly effective method of birth control during the study and for 30 days following the last dose of study drug. Effective contraceptive methods include the following (not applicable for Germany): • Double-barrier method (contraceptive sponge, diaphragm, or cervical cap with spermicidal jellies or creams PLUS male condom). • Progestogen-only hormonal contraception, where inhibition of ovulation is not the primary mode of action, PLUS condom with or without spermicide. Highly effective contraceptive methods include the following: • Nonhormonal methods: – Intrauterine device. – Bilateral tubal occlusion. – Vasectomized partner (provided that partner is the sole sexual partner of the trial participant and that the vasectomized partner has received medical assessment of the surgical success). Sexual abstinence: Sexual abstinence may be considered as a method only if defined as refraining from heterosexual intercourse and determined to be the usual lifestyle before entering the study with reliability of abstinence for the duration of the study participation and for 30 days after last dose of study drug. • Hormonal methods: – Combined (estrogen and progestogen) hormonal contraception associated with inhibition of ovulation, initiated at least 3 months before the first dose of study drug OR combined with a barrier method (male condom, female condom or diaphragm) if for shorter duration until she has been on contraceptive for 3 months. – Progestogen-only hormonal contraception associated with inhibition of ovulation, initiated at least 3 months before the first dose of study drug OR combined with a barrier method (male condom, female condom or diaphragm) if shorter until she has been on the contraceptive for 3 months."

Exclusion criteria 4

1. 01. Unstable, clinically significant neurologic (other than the disease being studied), psychiatric, cardiovascular, ophthalmologic, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, hematopoietic, endocrine disease, malignancy including progressive tumors, or other abnormality that may impact the ability to participate in the study or that may potentially confound the study results. It is the responsibility of the investigator to assess the clinical significance; however, consultation with the medical monitor may be warranted.
2. 02. Abnormal and clinically significant ECG abnormality at Visit 1 including QT interval with Fridericia correction method (QTcF) >450 ms confirmed with a repeat ECG using manual measurement of QTcF. Clinically significant ECG abnormalities should be discussed with the medical monitor.
3. 03. Subject is currently pregnant or breastfeeding or is planning to become pregnant during the study or within 30 days of the last dose of study drug.
4. 04. Subject is considered by the investigator to be at imminent risk of suicide or injury to self, others, or property. Subjects who have positive answers on item numbers 4 or 5 on the C SSRS before dosing are excluded. This scale will only be administered to subjects aged ≥6 years.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 6

1. 01. Incidence of TEAEs.
2. 02. Incidence of abnormal values for clinical laboratory tests and electrocardiogram (ECG) evaluations.
3. 03. Change from baseline in clinical laboratory test values, vital signs, Columbia-Suicide Severity Rating Scale (C-SSRS), and ECG parameters
4. 04. Change from baseline in height and weight for all age groups.
5. 05. Absolute value for Tanner stage for children 6 to 17 years of age during the study
6. 06. Absolute values for IGF-1 for children 2 to 17 years of age during the study

Secondary endpoints 7

1. 01. Percent change from baseline in total seizure frequency per 28 days for each (DS and LGS) cohort.
2. 02. Percent change from baseline in convulsive seizure frequency (DS) per 28 days
3. 03. Percent change from baseline in MMD seizure frequency (LGS) per 28 days
4. 04. Effect on the CGI-I and Care GI-I.
5. 05. Effect on CGI-I Seizure Intensity and Duration.
6. 06. Effect on the CGI-I Nonseizure Symptoms completed by clinician with input from the caregivers.
7. 07. Effect on QI-Disability.

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Takeda Development Center Americas Inc.

Sponsor organisation

Takeda Development Center Americas Inc.

Address

95 Hayden Avenue

City

Lexington

Postcode

02421-7942

Country

United States

Scientific contact point

Organisation

Takeda Development Center Americas Inc.

Contact name

Yasir Khan

Public contact point

Organisation

Takeda Development Center Americas Inc.

Contact name

Takeda

Third parties 17

Locations

10 EU/EEA countries · 35 investigational sites

By country

Investigational sites

Country notifications

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

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 15 files

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

Application history

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