A Study to Evaluate the Efficacy and Safety of TAK-861 for the Treatment of Narcolepsy with Cataplexy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Takeda Development Center Americas 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

3 Sep 2024 → 4 Jun 2025

Decision date (initial)

2024-08-13

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Takeda Development Center Americas, Inc.

External identifiers

EU CT number

2023-508465-32-00

ClinicalTrials.gov

NCT06470828

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To assess the effect of TAK-861 on EDS as measured by the Epworth Sleepiness Scale (ESS) total score.

Secondary objectives 8

1. To assess the effect of TAK-861 on excessive daytime sleepiness (EDS) as measured by the Maintenance of Wakefulness Test (MWT).
2. To assess the effect of TAK-861 on cataplexy as measured by the weekly cataplexy rate (WCR).
3. To assess the effect of TAK-861 on sustained attention as measured by the psychomotor vigilance test (PVT).
4. To assess the effect of TAK-861 on overall narcolepsy symptoms measured by the Patient Global Impression of Change (PGI-C) scale.
5. To assess the effect of TAK-861 on overall severity of narcolepsy symptoms measured by the Narcolepsy Severity Scale for Clinical Trials (NSS-CT).
6. To assess the efficacy of TAK-861 on functional impacts of narcolepsy as assessed by the Functional Impacts of Narcolepsy Instrument (FINI).
7. To assess the effect of TAK-861 on quality of life of participants, as assessed by the Short Form-36 Survey (SF-36).
8. To evaluate the safety of TAK-861 as measured by treatment-emergent adverse event (TEAE) incidence.

Conditions and MedDRA coding

Narcolepsy with Cataplexy (Narcolepsy Type 1)

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

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 6

1. Male or female participants aged 18 to 70 years, inclusive, at the time of signing the ICF.
2. The participant has a body mass index within the range 18 to 40 kg/m2 (inclusive).
3. The participant has an ICSD-3 or ICSD-3-TR diagnosis of NT1.
4. The participant has ≥4 partial or complete episodes of cataplexy/week (WCR).
5. The participant is positive for the human leukocyte antigen (HLA) genotype HLA-DQB1*06:02 or results from radioimmunoassay indicate the participant’s CSF OX/hypocretin-1 concentration is <110 pg/mL
6. The participant is judged by the investigator to be sufficiently healthy to participate in the study, based on clinical evaluations including laboratory safety tests, medical history, physical examination, 12-lead electrocardiogram (ECG), and vital sign measurements performed at the screening visit and before the first dose of study drug.

Exclusion criteria 10

1. The participant has a current medical disorder, other than narcolepsy with cataplexy, associated with EDS.
2. The participant has a history of myocardial infarction, has a history of clinically significant hepatic disease, thyroid disease, coronary artery disease, cardiac rhythm abnormality or heart failure; or has any medical condition (such as unstable cardiovascular, pulmonary, renal or gastrointestinal disease
3. The participant has current or recent (within 6 months) gastrointestinal disease that is expected to influence the absorption of drugs.
4. The participant has a history of cancer in the past 5 years (does not apply to participants with carcinoma in situ that has been resolved without further treatment or basal cell carcinoma; these participants may be included after approval by the sponsor or designee).
5. The participant has a clinically significant history of head injury or head trauma.
6. The participant has a history of epilepsy, seizure, or convulsion.
7. The participant has any current unstable psychiatric disorder or current active major depressive episode (MDE) or an active MDE in the past 6 months.
8. The participant has a current history of significant multiple or severe allergies (eg, food, drug, latex allergy) or has had an anaphylactic reaction or significant intolerance to prescription or nonprescription drugs or food.
9. The participant has a known hypersensitivity to any component of the formulation of TAK-861 or related compounds.
10. The participant has had major surgery or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks before the screening visit.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline to Week 12 in ESS total score

Secondary endpoints 8

1. Change from baseline to Week 12 in mean sleep latency from the 4 MWT wake trials.
2. WCR at Week 12
3. Change from baseline to Week 12 in mean number of lapses on the PVT
4. PGI-C score at Week 12.
5. Change from baseline to Week 12 in NSS-CT total score
6. Change from baseline to Week 12 in FINI domain scores for: Tiredness, Cognitive Functioning, Cataplexy, Social Activities, Everyday Activities, and Everyday Responsibilities.
7. Change from baseline to Week 12 in SF-36 mental and physical component summary scores
8. Occurrence of at least 1 TEAE during the study including the follow-up period, as applicable

Investigational products

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

Test 2

Placebo 1

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

Takeda

Public contact point

Organisation

Takeda Development Center Americas Inc.

Contact name

Takeda

Third parties 12

Locations

6 EU/EEA countries · 18 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 78 files

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

Application history

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