Clinical trial NCT05687903: A Study of TAK-861 in Participants With Narcolepsy Type 1
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Narcolepsy Type 1
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2023-01-18
Enrollment: 112
Sex: ALL
Minimum age (years): 16
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in the Average Sleep Latency as Determined From the MWT at Week 8
timeFrame: Baseline, Week 8
Secondary outcomes:
measure: Change From Baseline in Epworth Sleepiness Scale (ESS) Total Score at Week 8
timeFrame: Baseline, Week 8
measure: Weekly Cataplexy Rate (WCR) at Week 8
timeFrame: Week 8
measure: Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE)
timeFrame: From first dose of the study drug up to end of the study (up to 3 months)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Sleep Disorders Center of Alabama
state: Alabama
city: Redwood City
country: United States
facility: Stanford Center for Sleep Sciences and Medicine
state: California
city: Santa Ana
country: United States
facility: SDS Clinical Trials, Inc.
state: California
city: Colorado Springs
country: United States
facility: Delta Waves LLC - Hunt - PPDS, Sleep Disorder and Research Center
state: Colorado
city: Orlando
country: United States
facility: Florida Pediatric Research Institute
state: Florida
city: Atlanta
country: United States
facility: Neurotrials Research
state: Georgia
city: Gainesville
country: United States
facility: Georgia Neuro Center
state: Georgia
city: Kansas City
country: United States
facility: University of Kansas Medical Center Research Institute, Inc.
state: Kansas
city: Newton
country: United States
facility: Neurocare Inc
state: Massachusetts
city: Novi
country: United States
facility: Henry Ford Medical Center - Columbus
state: Michigan
city: Chesterfield
country: United States
facility: St. Lukes Sleep Medicine and Research Center
state: Missouri
city: Denver
country: United States
facility: Research Carolina Elite
state: North Carolina
city: Huntersville
country: United States
facility: ARSM Research, LLC
state: North Carolina
city: Cincinnati
country: United States
facility: Intrepid Research
state: Ohio
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Dublin
country: United States
facility: Ohio Sleep Medicine Institute
state: Ohio
city: Charleston
country: United States
facility: Medical University of South Carolina - PPDS
state: South Carolina
city: Columbia
country: United States
facility: Bogan Sleep Consultants, LLC
state: South Carolina
city: Houston
country: United States
facility: Comprehensive Sleep Medicine Associates - Sugar Land
state: Texas
city: San Antonio
country: United States
facility: Sleep Therapy and Research Center
state: Texas
city: Norfolk
country: United States
facility: Children's Specialty Group
state: Virginia
city: Glebe
country: Australia
facility: Woolcock Institute of Medical Research, Sleep and Circadian Research Group
state: New South Wales
city: Helsinki
country: Finland
facility: Terveystalo Helsinki Sleep Clinic
state: Uusimaa
city: Toulouse
country: France
facility: Hopital Pierre-Paul Riquet
state: Haute-Garonne
city: Montpellier
country: France
facility: CHU Gui De Chauliac
state: Herault
city: La Tronche
country: France
facility: CHU de Grenoble
state: Isere
city: Paris
country: France
facility: Hopital de la Pitie Salpetriere
city: Regensburg
country: Germany
facility: Universitaet Regensburg am Bezirksklinikum
state: Bayern
city: Schwerin
country: Germany
facility: Somni Bene Institut fur Medizinische Forschung und Schlafmedizin Schwerin GmbH
state: Mecklenburg-Vorpommern
city: Berlin
country: Germany
facility: Charite - Universitatsmedizin Berlin
city: Hamburg
country: Germany
facility: Klinische Forschung Hamburg
city: Bellaria
country: Italy
facility: IRCCS Istituto delle Scienze Neurologiche di Bologna, Dipartimento di Scienze Biomediche e Neuromotorie
state: Bologna
city: Roma
country: Italy
facility: Fondazione PTV Policlinico Tor Vergata, Centro del Sonno e del Trattamento Neurologico delle Fragilta
state: Lazio
city: Pozzilli
country: Italy
facility: Istituto Neurologico Mediterraneo Neuromed, Centro Per La Diagnosi E la Cura Del Sonno
state: Molise
city: Akita-Shi
country: Japan
facility: Akita University Hospital
state: Akita
city: Kurume-Shi
country: Japan
facility: Kurume University Hospital
state: Hukuoka
city: Kumamoto-Shi
country: Japan
facility: Howakai Kuwamizu Hospital, Chuo-Ku
state: Kumamoto
city: Osaka-Shi
country: Japan
facility: Gokeikai Osaka Kaisei Hospital, Yodogawa-Ku
state: Osaka
city: Bunkyo-Ku
country: Japan
facility: Koishikawa Tokyo Hospital
state: Tokyo
city: Kodaira-Shi
country: Japan
facility: National Center of Neurology and Psychiatry
state: Tokyo
city: Shibuya-Ku
country: Japan
facility: Yoyogi Sleep Disorder Center
state: Tokyo
city: Nagakute
country: Japan
facility: Aichi Medical University Hospital
city: Yokohama
country: Japan
facility: RESM respiratory and sleep medical-care clinic, Yokoharna Building, 4Floor
city: Heeze
country: Netherlands
facility: Kempenhaeghe - PPDS
state: Noord-Brabant
city: Heemstede
country: Netherlands
facility: Slaap-Waakcentrum SEIN Heemstede
state: Noord-Holland
city: Oslo
country: Norway
facility: University of Oslo
city: Vitoria
country: Spain
facility: Hospital Universitario Araba Santiago, Unidad Funcional de Sueno
state: Alava
city: Castellón De La Plana
country: Spain
facility: Hospital General de Castello, Sleep Unit
state: Castellon
city: Alzira
country: Spain
facility: Hospital de La Ribera, Unidad de Sueno
state: Valencia
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron - PPDS
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona, Neurology Service, scale 8-4th floor
city: Madrid
country: Spain
facility: Instituto de Investigaciones del Sueno
city: Madrid
country: Spain
facility: Hospital Vithas Madrid Arturo Soria
city: Goteborg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset
state: Vastra Gotalands Lan
city: Barmelweid
country: Switzerland
facility: Klinik Barmelweid AG
state: Aargau (de)
city: Lugano
country: Switzerland
facility: Neurocenter of Southern Switzerland
state: Ticino (it)
city: Bern
country: Switzerland
facility: Universitaetsspital Bern, Department of Neurology
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: