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

A Randomized, Double-blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of TAK-861 for the Treatment of Narcolepsy With Cataplexy (Narcolepsy Type 1)

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.

Study Overview

• Status: Completed
• Conditions: Narcolepsy Type 1
• Intervention / Treatment: Drug: Placebo; Drug: 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 Type: Interventional
• Enrollment (Actual): 112
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Glebe, New South Wales, Australia, 2037
      • Woolcock Institute of Medical Research, Sleep and Circadian Research Group
• Finland
  • Uusimaa
    • Helsinki, Uusimaa, Finland, 00380
      • Terveystalo Helsinki Sleep Clinic
• France
  • Paris, France, 75013
    • Hopital de la Pitie Salpetriere
  • Haute-Garonne
    • Toulouse, Haute-Garonne, France, 31000
      • Hôpital Pierre-Paul Riquet
  • Herault
    • Montpellier, Herault, France, 34090
      • CHU Gui de Chauliac
  • Isere
    • La Tronche, Isere, France, 38700
      • Chu de Grenoble
• Germany
  • Berlin, Germany, 10117
    • Charité - Universitätsmedizin Berlin
  • Hamburg, Germany, 20253
    • Klinische Forschung Hamburg
  • Bayern
    • Regensburg, Bayern, Germany, 93053
      • Universitaet Regensburg am Bezirksklinikum
  • Mecklenburg-Vorpommern
    • Schwerin, Mecklenburg-Vorpommern, Germany, 19053
      • Somni Bene Institut für Medizinische Forschung und Schlafmedizin Schwerin GmbH
• Italy
  • Bologna
    • Bellaria, Bologna, Italy, 40139
      • IRCCS Istituto delle Scienze Neurologiche di Bologna, Dipartimento di Scienze Biomediche e Neuromotorie
  • Lazio
    • Roma, Lazio, Italy, 00133
      • Fondazione PTV Policlinico Tor Vergata, Centro del Sonno e del Trattamento Neurologico delle Fragilta
  • Molise
    • Pozzilli, Molise, Italy, 86077
      • Istituto Neurologico Mediterraneo Neuromed, Centro Per La Diagnosi E la Cura Del Sonno
• Japan
  • Nagakute, Japan, 480-1195
    • Aichi Medical University Hospital
  • Yokohama, Japan, 222-0033
    • RESM respiratory and sleep medical-care clinic, Yokoharna Building, 4Floor
  • Akita
    • Akita-Shi, Akita, Japan, 010-8543
      • Akita University Hospital
  • Hukuoka
    • Kurume-Shi, Hukuoka, Japan, 830-0011
      • Kurume University Hospital
  • Kumamoto
    • Kumamoto-Shi, Kumamoto, Japan, 862-0954
      • Howakai Kuwamizu Hospital, Chuo-Ku
  • Osaka
    • Osaka-Shi, Osaka, Japan, 532-0003
      • Gokeikai Osaka Kaisei Hospital, Yodogawa-Ku
  • Tokyo
    • Bunkyo-Ku, Tokyo, Japan, 112-0012
      • Koishikawa Tokyo Hospital
    • Kodaira-Shi, Tokyo, Japan, 187-8551
      • National Center of Neurology and Psychiatry
    • Shibuya-Ku, Tokyo, Japan, 151-0053
      • Yoyogi Sleep Disorder Center
• Netherlands
  • Noord-Brabant
    • Heeze, Noord-Brabant, Netherlands, 5591 VE
      • Kempenhaeghe - PPDS
  • Noord-Holland
    • Heemstede, Noord-Holland, Netherlands, 2103 SW
      • Slaap-Waakcentrum SEIN Heemstede
• Norway
  • Oslo, Norway, 0450
    • University of Oslo
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron - PPDS
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona, Neurology Service, scale 8-4th floor
  • Madrid, Spain, 28036
    • Instituto de Investigaciones del Sueno
  • Madrid, Spain, 28046
    • Hospital Vithas Madrid Arturo Soria
  • Alava
    • Vitoria, Alava, Spain, 01004
      • Hospital Universitario Araba Santiago, Unidad Funcional de Sueno
  • Castellon
    • Castellón De La Plana, Castellon, Spain, 12004
      • Hospital General de Castello, Sleep Unit
  • Valencia
    • Alzira, Valencia, Spain, 46600
      • Hospital de La Ribera, Unidad de Sueno
• Sweden
  • Vastra Gotalands Lan
    • Goteborg, Vastra Gotalands Lan, Sweden, 413 46
      • Sahlgrenska Universitetssjukhuset
• Switzerland
  • Bern, Switzerland, 3010
    • Universitaetsspital Bern, Department of Neurology
  • Aargau (de)
    • Barmelweid, Aargau (de), Switzerland, 5017
      • Klinik Barmelweid AG
  • Ticino (it)
    • Lugano, Ticino (it), Switzerland, 6900
      • Neurocenter of Southern Switzerland
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35213-1966
      • Sleep Disorders Center of Alabama
  • California
    • Redwood City, California, United States, 94063-3132
      • Stanford Center for Sleep Sciences and Medicine
    • Santa Ana, California, United States, 92705-8519
      • SDS Clinical Trials, Inc.
  • Colorado
    • Colorado Springs, Colorado, United States, 80918
      • Delta Waves LLC - Hunt - PPDS, Sleep Disorder and Research Center
  • Florida
    • Orlando, Florida, United States, 32803-1468
      • Florida Pediatric Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30342-1743
      • NeuroTrials Research
    • Gainesville, Georgia, United States, 30501-3883
      • Georgia Neuro Center
  • Kansas
    • Kansas City, Kansas, United States, 66160-0001
      • University of Kansas Medical Center Research Institute, Inc.
  • Massachusetts
    • Newton, Massachusetts, United States, 02459-3233
      • Neurocare Inc
  • Michigan
    • Novi, Michigan, United States, 48377
      • Henry Ford Medical Center - Columbus
  • Missouri
    • Chesterfield, Missouri, United States, 63017-3406
      • St. Lukes Sleep Medicine and Research Center
  • North Carolina
    • Denver, North Carolina, United States, 28037
      • Research Carolina Elite
    • Huntersville, North Carolina, United States, 28078-5082
      • ARSM Research, LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45227-2172
      • Intrepid Research
    • Cleveland, Ohio, United States, 44195-0001
      • The Cleveland Clinic Foundation
    • Dublin, Ohio, United States, 43017-3521
      • Ohio Sleep Medicine Institute
  • South Carolina
    • Charleston, South Carolina, United States, 29425-5712
      • Medical University of South Carolina - PPDS
    • Columbia, South Carolina, United States, 29201-2923
      • Bogan Sleep Consultants, LLC
  • Texas
    • Houston, Texas, United States, 77030-2042
      • Comprehensive Sleep Medicine Associates - Sugar Land
    • San Antonio, Texas, United States, 78229-4849
      • Sleep Therapy and Research Center
  • Virginia
    • Norfolk, Virginia, United States, 23510-1021
      • Children's Specialty Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants received placebo tablets matching TAK-861, orally, twice daily (BID), from Days 1 to 56.	Drug: Placebo; Placebo oral tablets matching TAK-861
Experimental: TAK-861 0.5 mg BID; Participants received TAK-861 0.5 milligrams (mg), orally, BID, from Days 1 to 56.	Drug: TAK-861; TAK-861 oral tablets
Experimental: TAK-861 2 mg BID; Participants received TAK-861 2 mg, orally, BID, from Days 1 to 56.	Drug: TAK-861; TAK-861 oral tablets
Experimental: TAK-861 2 mg and 5 mg; Participants received TAK-861 2 mg followed by 5 mg dose, orally, BID, from Days 1 to 56.	Drug: TAK-861; TAK-861 oral tablets
Experimental: TAK-861 7 mg QD; Participants received TAK-861 7 mg, orally, once daily (QD), from Day 1 to 56. Placebo was given as the second dose.	Drug: Placebo; Placebo oral tablets matching TAK-861; Drug: TAK-861; TAK-861 oral tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Average Sleep Latency as Determined From the MWT at 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.	Baseline, Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Epworth Sleepiness Scale (ESS) Total Score at 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.	Baseline, Week 8
Weekly Cataplexy Rate (WCR) at 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.	Week 8
Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE)	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.	From first dose of the study drug up to end of the study (up to 3 months)

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Study Director, Takeda

Publications and helpful links

Helpful Links

• To obtain more information on the study, click here/on this link

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2023
• Primary Completion (Actual): December 14, 2023
• Study Completion (Actual): December 14, 2023

Study Registration Dates

• First Submitted: January 9, 2023
• First Submitted That Met QC Criteria: January 9, 2023
• First Posted (Actual): January 18, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 13, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Nervous System Diseases; Mental Disorders; Sleep Wake Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Disorders of Excessive Somnolence; Narcolepsy
• Other Study ID Numbers: TAK-861-2001; U1111-1277-4261 (Other Identifier: WHO); 2022-001654-38 (EudraCT Number); jRCT2031220644 (Registry Identifier: jRCT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (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.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No