Randomized Study of XEN1101 Versus Placebo in Focal-Onset Seizures (X-TOLE2)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Xenon Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

11 Aug 2023 → 3 Feb 2026

Decision date (initial)

2023-04-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Xenon Pharmaceuticals Inc.

External identifiers

EU CT number

2022-502000-73-00

ClinicalTrials.gov

NCT05614063

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Others, Safety

To assess the effect of XEN1101 versus placebo on reducing focal seizure frequency.

Secondary objectives 2

1. To assess the early treatment effect of XEN1101 versus placebo on focal seizure frequency
2. To assess the effect of XEN1101 versus placebo on seizure impact.

Conditions and MedDRA coding

Focal Onset Seizures

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Subject is properly informed of the nature and risks of the study and gives informed consent in writing prior to entering the study.
2. Subject has a diagnosis (≥2 years) of focal epilepsy according to the International League Against Epilepsy 2017 classification criteria. Subject must have had adequate trials of at least 2 ASMs, which were given (and tolerated) at adequate therapeutic doses, without achieving sustained seizure freedom.
3. Subject is on a stable dose of 1 to 3 allowable current ASMs for at least 1 month prior to screening (Visit 1), during screening/baseline, and throughout the DBP.
4. Subject is able to keep accurate seizure diaries.

Exclusion criteria 9

1. Subject has previously documented electroencephalogram which shows any pattern not consistent with focal etiology of seizures.
2. Subject has history of focal aware non-motor seizures only
3. Subject has a history of non-epileptic psychogenic seizures.
4. Subject has history of a primary generalized seizure.
5. Subject has presence or history of a developmental and epileptic encephalopathy, including Lennox-Gastaut syndrome.
6. Subject has seizures secondary to drug or alcohol use, ongoing infection, neoplasia, demyelinating disease, degenerative neurological disease, metabolic illness, progressive structural lesion, encephalopathy, or progressive CNS disease.
7. Subject has history of status epilepticus or repetitive seizures within the 12-month period preceding Visit 1 where the individual seizures cannot be counted.
8. Subject has history of neurosurgery for seizures <1 year prior to Visit 1, or radiosurgery <2 years prior to enrollment.
9. Any medical condition or personal circumstance that, in the opinion of the investigator, exposes the subject to unacceptable risk by participating in the study or prevents adherence to the protocol

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of subjects experiencing ≥50% reduction in monthly (28 days) focal seizure frequency from baseline through the DBP for XEN1101 versus placebo

Secondary endpoints 3

1. MPC in monthly (28 days) focal seizure frequency from baseline through the DBP for XEN1101 versus placebo
2. Proportion of subjects experiencing ≥50% reduction in weekly (7 days) focal seizure frequency from baseline to Week 1.
3. Proportion of subjects experiencing “at least much improved” (including “much” and “very much improved”) in PGI-C at Week 12.

Investigational products

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

Test 4

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Xenon Pharmaceuticals Inc.

Sponsor organisation

Xenon Pharmaceuticals Inc.

Address

3650 Gilmore Way

City

Burnaby

Postcode

V5G 4W8

Country

Canada

Scientific contact point

Organisation

Xenon Pharmaceuticals Inc.

Contact name

Daniela Nenciu

Public contact point

Organisation

Xenon Pharmaceuticals Inc.

Contact name

Xenon Medical Affairs

Third parties 11

Locations

9 EU/EEA countries · 38 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

Documents 206 files

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

Application history

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