A Study to Investigate the Effects of Cleminorexton Compared With Placebo in the Treatment of Participants With Central Disorders of Hypersomnolence

June 1, 2026 updated by: Centessa Pharmaceuticals (UK) Limited

A Randomized, Double-blind, 3-Arm Parallel Design Study to Investigate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Cleminorexton Compared With Placebo in Participants With Central Disorders of Hypersomnolence

Narcolepsy Type 1 (NT1) and Narcolepsy Type 2 (NT2) are rare conditions that make people feel very sleepy during the day (often referred to as excessive daytime sleepiness [EDS]). People living with these conditions might find it hard to stay alert and pay attention when they are at school, working, driving, or performing other daily activities.

While all conditions result in feeling sleepy, there are some differences in other common symptoms:

  • NT1: People with NT1 often feel very tired during the day and experience cataplexy. Cataplexy is a sudden loss of muscle strength, which can cause someone to collapse or lose control of their muscles for a short time. This is often triggered by strong emotions, such as laughter or surprise. They may also have trouble sleeping well at night.
  • NT2: People with NT2 feel sleepy during the day, just like NT1, but they do not have cataplexy.

Orexin is a protein in the brain that helps coordinate a system that plays an important role in helping people to stay awake during the daytime. Cleminorexton is designed to mimic the action of orexin. The purpose of this study is to see how safe and tolerable cleminorexton is in NT1 and NT2 and learn about what the drug does to the body. Another goal of the study is to see if cleminorexton can help people with NT1 and NT2 feel less sleepy and make other symptoms better.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The SAPPHIRE Clinical Trial

The Sponsor may in the future, through a protocol amendment, expand the protocol to include participants with idiopathic hypersomnia (IH) in Cohort C.

Study Type

Interventional

Enrollment (Estimated)

222

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • South Carolina
      • Columbia, South Carolina, United States, 29201
        • Recruiting
        • Columbia, South Carolina

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  • 18-70 years of age
  • Body Mass Index (BMI) within the range ≥ 17.0 and ≤ 45 kg/m^2 (inclusive)
  • Meets the diagnostic criteria of Narcolepsy Type 1 (NT1) or Type 2 (NT2) according to International Classification of Sleep Disorders, 3rd edition, Text Revision edition (ICSD-3-TR) criteria
  • Is willing and able to discontinue all medications used for the treatment of narcolepsy
  • Is willing and able to adhere to additional protocol requirements

Key Exclusion Criteria:

  • Medical disorder other than NT1 or NT2, that is associated with excessive daytime sleepiness (EDS)
  • Presence of significant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, hematological, malignancy, endocrine, neurological or psychiatric disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group A - Narcolepsy Type 1 (Dose 1)
Drug: cleminorexton
Oral cleminorexton capsule
Experimental: Group A - Narcolepsy Type 1 (Dose 2)
Drug: cleminorexton
Oral cleminorexton capsule
Placebo Comparator: Group A - Narcolepsy Type 1 (placebo)
Drug: Placebo
matching placebo capsule
Experimental: Group B - Narcolepsy Type 2 (Dose 1)
Drug: cleminorexton
Oral cleminorexton capsule
Experimental: Group B - Narcolepsy Type 2 (Dose 2)
Drug: cleminorexton
Oral cleminorexton capsule
Placebo Comparator: Group B - Narcolepsy Type 2 (placebo)
Drug: Placebo
matching placebo capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change from baseline in mean sleep latency (average of the first 4 trials) on the Maintenance of Wakefulness Test (MWT)
Time Frame: Baseline to week 12
Baseline to week 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline in Epworth Sleepiness Scale (ESS) total score
Time Frame: Baseline to Week 12
Baseline to Week 12
Weekly Cataplexy Rate (WCR)
Time Frame: Week 12
Measurement specific to Group A
Week 12
Change from baseline in Narcolepsy Severity Scale for Clinical Trials (NSS-CT)
Time Frame: Baseline to Week 12
Measurement specific to Group A
Baseline to Week 12
Change from baseline in Narcolepsy Severity Scale-2 for Clinical Trials (NSS2-CT) total score
Time Frame: Baseline to Week 12
Measurement specific to Group B
Baseline to Week 12
Incidence, Severity, and casual relationship of participants with Treatment Emergent Adverse Events (TEAEs)
Time Frame: Baseline to Week 12
Baseline to Week 12
Number of participants with abnormal changes from baseline in clinical laboratory tests
Time Frame: Baseline to Week 12
Baseline to Week 12
Number of participants with abnormal changes from baseline in vital signs
Time Frame: Baseline to Week 12
Baseline to Week 12
Number of participants with abnormal changes from baseline in 12-lead electrocardiograms (ECGs)
Time Frame: Baseline to Week 12
Baseline to Week 12
Number of participants with at least 1 endorsement of Item 4 or 5 on Columbia-Suicide Severity Rating Scale (C-SSRS)
Time Frame: Baseline to Week 12
Baseline to Week 12
Cmax: Maximum observed plasma concentration
Time Frame: Baseline to Week 12
Baseline to Week 12
Tmax: Time of Maximum Concentration for cleminorexton
Time Frame: Baseline to Week 12
Baseline to Week 12
AUC: Area under the plasma concentration-time curve
Time Frame: Baseline to Week 12
Baseline to Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centessa Pharmaceuticals (UK) Limited

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 15, 2026

Primary Completion (Estimated)

September 30, 2027

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

April 27, 2026

First Submitted That Met QC Criteria

May 13, 2026

First Posted (Actual)

May 20, 2026

Study Record Updates

Last Update Posted (Actual)

June 3, 2026

Last Update Submitted That Met QC Criteria

June 1, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ORX750-004

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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