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NCT Number: NCT07598708

A Study to Investigate the Effects of Cleminorexton Compared With Placebo in the Treatment of 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.

Recruiting

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Key information

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Miami, Florida, Miami, Florida, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

cleminorexton

Drug

Oral cleminorexton capsule

Placebo

Drug

matching placebo capsule

Primary outcomes

  1. 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

Secondary outcomes

  1. Change from baseline in Epworth Sleepiness Scale (ESS) total score

    Time frame: Baseline to Week 12

  2. Weekly Cataplexy Rate (WCR)

    Time frame: Week 12

    Measurement specific to Group A

  3. Change from baseline in Narcolepsy Severity Scale for Clinical Trials (NSS-CT)

    Time frame: Baseline to Week 12

    Measurement specific to Group A

  4. 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

  5. Incidence, Severity, and casual relationship of participants with Treatment Emergent Adverse Events (TEAEs)

    Time frame: Baseline to Week 12

  6. Number of participants with abnormal changes from baseline in clinical laboratory tests

    Time frame: Baseline to Week 12

  7. Number of participants with abnormal changes from baseline in vital signs

    Time frame: Baseline to Week 12

  8. Number of participants with abnormal changes from baseline in 12-lead electrocardiograms (ECGs)

    Time frame: Baseline to Week 12

  9. 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

  10. Cmax: Maximum observed plasma concentration

    Time frame: Baseline to Week 12

  11. Tmax: Time of Maximum Concentration for cleminorexton

    Time frame: Baseline to Week 12

  12. AUC: Area under the plasma concentration-time curve

    Time frame: Baseline to Week 12

Study contacts

Contact information is provided by the study sponsor or research team.

Centessa Pharmaceuticals

CONTACT

[email protected]

617-468-5770

Sponsors and collaborators

Lead sponsor

Centessa Pharmaceuticals (UK) Limited

Industry

Registry information

Official study title

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

Important dates

Study start
2026
Primary completion
2027
Study completion
2027
First posted
May 20, 2026
Registry last updated
Jul 13, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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