Clinical Trials Register

Summary
EudraCT Number:	2021-002481-40
Sponsor's Protocol Code Number:	TAK-935-3002
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-09-17
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Poland - Office for Medicinal Products

A.2

EudraCT number

2021-002481-40

A.3

Full title of the trial

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy, Safety, and Tolerability of Soticlestat as Adjunctive Therapy in Pediatric and Adult Subjects With Lennox-Gastaut Syndrome (LGS)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Study of Soticlestat as Adjunctive Therapy in Pediatric and Adult Subjects With Lennox-Gastaut Syndrome

A.4.1

Sponsor's protocol code number

TAK-935-3002

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/491/2021

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Takeda Development Center Americas, Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Takeda Development Center Americas, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Takeda Development Center Americas, Inc.
B.5.2	Functional name of contact point	Associate Medical Director
B.5.3	Address:
B.5.3.1	Street Address	95 Hayden Avenue
B.5.3.2	Town/ city	Lexington, MA
B.5.3.3	Post code	02421
B.5.3.4	Country	United States
B.5.4	Telephone number	+1 781 774 9968
B.5.6	E-mail	yasir.khan@takeda.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EMA/OD/0000066312
D.3 Description of the IMP
D.3.1	Product name	soticlestat
D.3.2	Product code	TAK-935
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Gastroenteral use Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	soticlestat
D.3.9.1	CAS number	1429505-03-2
D.3.9.2	Current sponsor code	TAK-935
D.3.9.4	EV Substance Code	SUB198078
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EMA/OD/0000066312
D.3 Description of the IMP
D.3.1	Product name	Soticlestat
D.3.2	Product code	TAK-935
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Gastroenteral use Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	soticlestat
D.3.9.1	CAS number	1429505-03-2
D.3.9.2	Current sponsor code	TAK-935
D.3.9.4	EV Substance Code	SUB198078
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Lennox-Gastaut Syndrome (LGS)

E.1.1.1

Medical condition in easily understood language

Seizures

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	PT
E.1.2	Classification code	10048816
E.1.2	Term	Lennox-Gastaut syndrome
E.1.2	System Organ Class	10029205 - Nervous system disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

- To assess the efficacy and safety of soticlestat in reducing MMD seizure frequency as add-on therapy to standard of care (SOC) as compared with placebo during the full treatment period (titration + maintenance).

For European Medicines Agency (EMA) registration:
- To assess the efficacy and safety of soticlestat in reducing MMD seizure frequency as add-on
therapy to SOC compared with placebo during the maintenance period only.

E.2.2

Secondary objectives of the trial

To assess the following in subjects taking soticlestat as compared with placebo during the full treatment period, unless otherwise noted:
- Proportion of treatment responders defined as those with ≥50% reduction in MMD seizures from baseline during the maintenance period and the full treatment period.
-Effect on total seizure frequency of all seizure types during the maintenance period and the full treatment period.
- Change from baseline in proportion of MMD seizure-free days.
- Longest MMD seizure-free interval.
- Number of days when rescue ASMs are used.
- Effect on the Clinical Global Impression of Improvement (CGI-I) (clinician) and Caregiver Global Impression of Improvement (Care GI-I).
- Effect on CGI-I Seizure Intensity and Duration.
- Effect on the CGI-I Nonseizure Symptoms completed by clinician with input from the caregiver.
- Effect on Quality of Life Inventory-Disability (QI-Disability).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Has documented clinical diagnosis of LGS.
2. Has had ≥8 MMD seizures each month in the 3 months prior to Screening based on the historical information and has had ≥8 MMD seizures per 28 days during the 4 to 6 week prospective Baseline Period.
3. Weighs ≥10 kg at the Screening Visit (Visit 1).
4. Failure to control seizures despite appropriate trials of at least 1 ASM based on historical information, and is currently on an antiseizure
therapy or other treatment options considered as standard of care (SOC).
5. Artisanal cannabidiols are allowed at a stable dose for at least 4 weeks before the screening visit (Visit 1); the dosing regimen and manufacturer should remain constant throughout the study. (Artisanal
cannabidiols will not be counted as ASMs.)
6. Currently taking 0 to 3 ASMs at stable doses for at least 4 weeks before the Screening Visit (Visit 1); Fenfluramine and cannabidiol
(Epidiolex) are allowed where available and counted as an ASM. ASM
dosing regimen must remain constant throughout the study.

E.4

Principal exclusion criteria

1. Admitted to a medical facility and intubated for treatment of status
epilepticus 2 or more times in the 3 months immediately before
Screening (Visit 1). For the purpose of this exclusion criterion, status is
defined as continuous seizure activity lasting longer than 5 minutes or
repeated seizures without return to Baseline in between seizures.
2. 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.
3. Considered by the investigator to be at imminent risk of suicide or
injury to self, others, or property, or the participant has attempted
suicide within 12 months before the Screening Visit (Visit 1).
Participants who have positive answers on item numbers 4 or 5 on the
Columbia suicide severity rating scale (C-SSRS) before dosing (Visit 2)
are excluded. This scale will only be administered to participants aged ≥
6 years.

E.5 End points

E.5.1

Primary end point(s)

- Percent change from baseline in MMD seizure frequency per 28 days in subjects receiving soticlestat as compared with placebo during the full treatment period.
For European Medicines Agency (EMA) registration:
- Percent change from baseline in MMD seizure frequency per 28 days in subjects receiving soticlestat as compared with placebo during the maintenance period.

E.5.1.1

Timepoint(s) of evaluation of this end point

Primary end points will be assessed throughout the study.

E.5.2

Secondary end point(s)

To assess the following in subjects receiving soticlestat as compared with placebo during the full treatment period, unless otherwise noted:
- Proportion of responders defined as those with ≥50% reduction from baseline in MMD seizures during the maintenance period and the full treatment period.
- Responder analysis of the proportion of subjects with ≤0%, >0% to ≤25%, >25% to ≤50%, >50% to ≤75%, and >75% to ≤100% reduction from baseline in MMD seizures in a cumulative response curve.
- Care GI-I (caregiver).
- CGI-I (clinician).
- CGI-I Nonseizure Symptoms.
- Change in QI-Disability score
- CGI-I Seizure Intensity and Duration.
- Percent change from baseline in frequency of all seizures per 28 days during the maintenance period and the full treatment period.
- Percent change from baseline in MMD seizure frequency per 28 days during the maintenance period.
- Change from baseline in proportion of MMD seizure-free days.
- Longest MMD seizure-free interval.
- Number of days when rescue ASM is used.

E.5.2.1

Timepoint(s) of evaluation of this end point

Secondary end points will be assessed throughout the study.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Ukraine

Australia

Canada

China

Japan

Russian Federation

Serbia

United States

Belgium

France

Germany

Greece

Hungary

Italy

Latvia

Netherlands

Poland

Spain

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The end of study for an individual subject who does not enroll in the OLE study on the same day as Visit 11/early termination is either: - The day of the scheduled safety follow-up phone call or visit. OR - Midnight of the day after Visit 11/early termination but before the scheduled safety follow-up phone call. The end of study for an individual subject who enrolls in the OLE study on the same day as Visit 11/early termination is midnight of that same day.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

164

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

105

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

children and adolescents between 2 -18 and adults incapable of giving
consent

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

234

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Study drug will not be available upon completion of the subject's participation in the study. The subject should be returned to the care of a physician and standard therapies initiated or resumed as required.
However, following completion of the study, subjects will have the option to enroll in an OLE study, as per the OLE study's inclusion/exclusion criteria.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-10-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-09-23

P. End of Trial
P.	End of Trial Status	Ongoing

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