A Study of TAK-861 in Participants With Narcolepsy Type 1

Phase 2

Completed

• Conditions: Narcolepsy Type 1
• Interventions: Drug: Placebo; Drug: TAK-861

• Registration Number: NCT05687903
• Lead Sponsor: Takeda

Brief Summary

The main aim of this study is to see how TAK-861 works on symptoms of narcolepsy, including excessive daytime sleepiness and cataplexy. Approximately 100 participants will take part in the study across North America, Europe and Asia Pacific.

The treatment (TAK-861 or placebo) will be administered for 8 or 12 weeks. After this treatment period the participant will have the option to participate in a separate, long- term extension study during which all participants will be treated with TAK-861.

Detailed Description

The drug being tested in this study is called TAK-861. This study will look at the effect of TAK-861 on improvement in narcolepsy symptoms, including excessive daytime sleepiness (EDS) and number of cataplexy episodes.

The study will enroll approximately 100 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the five treatment groups which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):

* TAK-861 Dose 1

* TAK-861 Dose 2

* TAK-861 Dose 3

* TAK-861 Dose 4

* Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient

This multi-center trial will be conducted worldwide. The overall time to participate in this study is up to 23 weeks. Participants will make multiple visits to the clinic during the treatment period and then will either enroll in a long-term extension study in which all participants will receive TAK-861 or have 2 final visits 7 and 28 days after last dose of study drug for follow-up assessments.

Study Timeline

• Study Start: 2023-01-09
• Study First Submitted: 2023-01-09
• Study First Submitted QC: 2023-01-09
• Study First Posted: 2023-01-18
• Primary Completion: 2023-12-14
• Study Completion: 2023-12-14
• Status Verified: 2024-12
• Results First Submitted: 2024-12-13
• Results First Submitted QC: 2024-12-13
• Last Update Submitted: 2024-12-13
• Results First Posted: 2025-01-09
• Last Update Posted: 2025-01-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 112

Inclusion Criteria

1. The participant is aged 18 to 70 years, inclusive, at the time of signing the informed consent form (ICF).

   Note: In Japan, participants aged 16 to 70 years, inclusive, may be included.

2. The participant has body mass index (BMI) within the range 18 to 40 kilogram per square meter [kg/m^2] (inclusive).

3. The participant has an International Classification of Sleep Disorders, 3rd Edition (ICSD-3) diagnosis of narcolepsy type 1 (NT1) by polysomnography (PSG)/Multiple Sleep Latency Test (MSLT), performed within the past 10 years.

4. The participant is positive for the human leukocyte antigen (HLA) genotype HLA-DQB1*06:02 or results from cerebrospinal fluid (CSF) testing indicate the participant's CSF orexin (OX)/hypocretin-1 concentration is <110 picograms per milliliter ([pg/mL] (or less than one-third of the mean values obtained in normal participants within the same standardized assay).

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Exclusion Criteria

1. The participant has a current medical disorder, other than narcolepsy with cataplexy, associated with EDS.

2. The participant has medically significant hepatic or thyroid disease.

3. 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 cancer).

4. The participant has clinically significant coronary artery disease, a history of myocardial infarction, clinically significant angina, clinically significant cardiac rhythm abnormality, or heart failure.

5. The participant has a clinically significant history of head injury or head trauma.

6. The participant has history of epilepsy, seizure, or convulsion, or has a family history of inherited disorders associated with seizure (except for a single febrile seizure in childhood).

7. The participant has one or more of the following psychiatric disorders:

   1. Any current unstable psychiatric disorder.
   2. Current or history of manic or hypomanic episode, schizophrenia or any other psychotic disorder, including schizoaffective disorder, major depression with psychotic features, bipolar depression with psychotic features, obsessive compulsive disorder, intellectual disability, organic mental disorders, or mental disorders due to a general medical condition as defined in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5).
   3. Current diagnosis or history of substance use disorder as defined in the DSM-5.
   4. Current active major depressive episode (MDE) or who have had an active MDE in the past 6 months.

8. The participant has a history of cerebral ischemia, transient ischemic attack (<5 years ago), intracranial aneurysm, or arteriovenous malformation.

9. The participant has a positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency virus (HIV) antibody/antigen.

10. The participant's renal creatinine clearance (Cockcroft-Gault Equation) is ≤50 mL/minute.

11. The participant has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) values >1.5 times the upper limit of normal (ULN).

12. The participant is 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 the past year.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants received placebo tablets matching TAK-861, orally, twice daily (BID), from Days 1 to 56.
TAK-861 0.5 mg BID	TAK-861	Participants received TAK-861 0.5 milligrams (mg), orally, BID, from Days 1 to 56.
TAK-861 2 mg BID	TAK-861	Participants received TAK-861 2 mg, orally, BID, from Days 1 to 56.
TAK-861 2 mg and 5 mg	TAK-861	Participants received TAK-861 2 mg followed by 5 mg dose, orally, BID, from Days 1 to 56.
TAK-861 7 mg QD	TAK-861	Participants received TAK-861 7 mg, orally, once daily (QD), from Day 1 to 56. Placebo was given as the second dose.
TAK-861 7 mg QD	Placebo	Participants received TAK-861 7 mg, orally, once daily (QD), from Day 1 to 56. Placebo was given as the second dose.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in the Average Sleep Latency as Determined From the MWT at Week 8	Baseline, Week 8	The MWT is a validated, objective measure that evaluates a participant's ability to remain awake under soporific conditions for a defined period. During each MWT session (1 session = 40 minutes), participants were instructed to sit quietly and remain awake for as long as possible. Sleep latency in each session was recorded on EEG. If no sleep was observed according to these rules, then the latency was defined as 40 minutes. The linear mixed effects model for repeated measures (MMRM) was used for analysis.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Epworth Sleepiness Scale (ESS) Total Score at Week 8	Baseline, Week 8	The ESS is a subjective, self-administered, validated scale (scored 0 to 3) to respond to each of the 8 questions of daily life that asks participants how likely they are to fall asleep in those situations. The scores are summed to give an overall score of 0 to 24. Higher scores indicate stronger subjective daytime sleepiness, and scores below 10 are considered to be within the normal range. The MMRM was used for analysis.
Weekly Cataplexy Rate (WCR) at Week 8	Week 8	Participants completed a daily patient-reported sleep diary to record self-reported narcolepsy symptoms. Participants recorded episodes of cataplexy attacks in the diary. The total number of events averaged for a week were reported. WCR = (total number of cataplexy attacks over a number of non-missing diary days for a given duration/number of non-missing diary days in that duration)\*7. The generalized estimating equations (GEE) model was used for analysis.
Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE)	From first dose of the study drug up to end of the study (up to 3 months)	An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of the study intervention, whether or not the occurrence was considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE was defined as an AE with an onset that occurred after receiving study drug.

Trial Locations

Locations (57)

Woolcock Institute of Medical Research, Sleep and Circadian Research Group; 🇦🇺 Glebe, New South Wales, Australia

Kurume University Hospital; 🇯🇵 Kurume-Shi, Hukuoka, Japan

Koishikawa Tokyo Hospital; 🇯🇵 Bunkyo-Ku, Tokyo, Japan

Akita University Hospital; 🇯🇵 Akita-Shi, Akita, Japan

CHU de Grenoble; 🇫🇷 La Tronche, Isere, France

Research Carolina Elite; 🇺🇸 Denver, North Carolina, United States

Slaap-Waakcentrum SEIN Heemstede; 🇳🇱 Heemstede, Noord-Holland, Netherlands

IRCCS Istituto delle Scienze Neurologiche di Bologna, Dipartimento di Scienze Biomediche e Neuromotorie; 🇮🇹 Bellaria, Bologna, Italy

ARSM Research, LLC; 🇺🇸 Huntersville, North Carolina, United States

Howakai Kuwamizu Hospital, Chuo-Ku; 🇯🇵 Kumamoto-Shi, Kumamoto, Japan

Hospital Vithas Madrid Arturo Soria; 🇪🇸 Madrid, Spain

Fondazione PTV Policlinico Tor Vergata, Centro del Sonno e del Trattamento Neurologico delle Fragilta; 🇮🇹 Roma, Lazio, Italy

Klinische Forschung Hamburg; 🇩🇪 Hamburg, Germany

Hospital de La Ribera, Unidad de Sueno; 🇪🇸 Alzira, Valencia, Spain

Universitaet Regensburg am Bezirksklinikum; 🇩🇪 Regensburg, Bayern, Germany

Hospital Clinic de Barcelona, Neurology Service, scale 8-4th floor; 🇪🇸 Barcelona, Spain

Aichi Medical University Hospital; 🇯🇵 Nagakute, Japan

Hospital General de Castello, Sleep Unit; 🇪🇸 Castellón De La Plana, Castellon, Spain

Kempenhaeghe - PPDS; 🇳🇱 Heeze, Noord-Brabant, Netherlands

Universitaetsspital Bern, Department of Neurology; 🇨🇭 Bern, Switzerland

Neurotrials Research; 🇺🇸 Atlanta, Georgia, United States

Ohio Sleep Medicine Institute; 🇺🇸 Dublin, Ohio, United States

Intrepid Research; 🇺🇸 Cincinnati, Ohio, United States

The Cleveland Clinic Foundation; 🇺🇸 Cleveland, Ohio, United States

Bogan Sleep Consultants, LLC; 🇺🇸 Columbia, South Carolina, United States

Comprehensive Sleep Medicine Associates - Sugar Land; 🇺🇸 Houston, Texas, United States

University of Kansas Medical Center Research Institute, Inc.; 🇺🇸 Kansas City, Kansas, United States

Istituto Neurologico Mediterraneo Neuromed, Centro Per La Diagnosi E la Cura Del Sonno; 🇮🇹 Pozzilli, Molise, Italy

Gokeikai Osaka Kaisei Hospital, Yodogawa-Ku; 🇯🇵 Osaka-Shi, Osaka, Japan

Yoyogi Sleep Disorder Center; 🇯🇵 Shibuya-Ku, Tokyo, Japan

Delta Waves LLC - Hunt - PPDS, Sleep Disorder and Research Center; 🇺🇸 Colorado Springs, Colorado, United States

Stanford Center for Sleep Sciences and Medicine; 🇺🇸 Redwood City, California, United States

Sleep Disorders Center of Alabama; 🇺🇸 Birmingham, Alabama, United States

Georgia Neuro Center; 🇺🇸 Gainesville, Georgia, United States

Neurocare Inc; 🇺🇸 Newton, Massachusetts, United States

Henry Ford Medical Center - Columbus; 🇺🇸 Novi, Michigan, United States

Children's Specialty Group; 🇺🇸 Norfolk, Virginia, United States

Sleep Therapy and Research Center; 🇺🇸 San Antonio, Texas, United States

Hopital Pierre-Paul Riquet; 🇫🇷 Toulouse, Haute-Garonne, France

Hopital de la Pitie Salpetriere; 🇫🇷 Paris, France

CHU Gui De Chauliac; 🇫🇷 Montpellier, Herault, France

Somni Bene Institut fur Medizinische Forschung und Schlafmedizin Schwerin GmbH; 🇩🇪 Schwerin, Mecklenburg-Vorpommern, Germany

Instituto de Investigaciones del Sueno; 🇪🇸 Madrid, Spain

RESM respiratory and sleep medical-care clinic, Yokoharna Building, 4Floor; 🇯🇵 Yokohama, Japan

Hospital Universitario Araba Santiago, Unidad Funcional de Sueno; 🇪🇸 Vitoria, Alava, Spain

Klinik Barmelweid AG; 🇨🇭 Barmelweid, Aargau (de), Switzerland

Sahlgrenska Universitetssjukhuset; 🇸🇪 Goteborg, Vastra Gotalands Lan, Sweden

Charite - Universitatsmedizin Berlin; 🇩🇪 Berlin, Germany

SDS Clinical Trials, Inc.; 🇺🇸 Santa Ana, California, United States

St. Lukes Sleep Medicine and Research Center; 🇺🇸 Chesterfield, Missouri, United States

Hospital Universitario Vall d'Hebron - PPDS; 🇪🇸 Barcelona, Spain

National Center of Neurology and Psychiatry; 🇯🇵 Kodaira-Shi, Tokyo, Japan

Neurocenter of Southern Switzerland; 🇨🇭 Lugano, Ticino (it), Switzerland

Terveystalo Helsinki Sleep Clinic; 🇫🇮 Helsinki, Uusimaa, Finland

University of Oslo; 🇳🇴 Oslo, Norway

Florida Pediatric Research Institute; 🇺🇸 Orlando, Florida, United States

Medical University of South Carolina - PPDS; 🇺🇸 Charleston, South Carolina, United States