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

NCT07598708 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: ORX750-004
• Study Type: interventional
• Target: 222
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Narcolepsy Type 1; Narcolepsy Type 2

Keywords

NT1; NT2; Excessive Daytime Sleepiness; Orexin Receptor 2 agonist; Central Disorders of Hypersomnia; Disorders of Excessive Somnolence; Dyssomnias; Nervous System Diseases; Mental Disorders; Hypersomnia; Hypersomnolence; Sleep Wake Disorders; Sleep Disorder; Sleep; Sleepiness; Cataplexy; Narcolepsy Type 1; Narcolepsy Type 2; Orexin; ORX750; Cleminorexton; Narcolepsy; SAPPHIRE

Outcome Measures

Primary Outcomes (1)

• Change from baseline in mean sleep latency (average of the first 4 trials) on the Maintenance of Wakefulness Test (MWT)

  Baseline to week 12

Secondary Outcomes (12)

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

  Baseline to Week 12

• Weekly Cataplexy Rate (WCR)

  Week 12

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

  Baseline to Week 12

• Change from baseline in Narcolepsy Severity Scale-2 for Clinical Trials (NSS2-CT) total score

  Baseline to Week 12

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

  Baseline to Week 12

Study Arms (6)

Group A - Narcolepsy Type 1 (Dose 1)

EXPERIMENTAL

Drug: cleminorexton

Group A - Narcolepsy Type 1 (Dose 2)

EXPERIMENTAL

Drug: cleminorexton

Group A - Narcolepsy Type 1 (placebo)

PLACEBO COMPARATOR

Drug: Placebo

Group B - Narcolepsy Type 2 (Dose 1)

EXPERIMENTAL

Drug: cleminorexton

Group B - Narcolepsy Type 2 (Dose 2)

EXPERIMENTAL

Drug: cleminorexton

Group B - Narcolepsy Type 2 (placebo)

PLACEBO COMPARATOR

Drug: Placebo

Interventions

cleminorexton DRUG

Oral cleminorexton capsule

Group A - Narcolepsy Type 1 (Dose 1); Group A - Narcolepsy Type 1 (Dose 2); Group B - Narcolepsy Type 2 (Dose 1); Group B - Narcolepsy Type 2 (Dose 2)

Placebo DRUG

matching placebo capsule

Group A - Narcolepsy Type 1 (placebo); Group B - Narcolepsy Type 2 (placebo)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centessa Pharmaceuticals (UK) Limited: lead

MeSH Terms

Conditions

Disorders of Excessive Somnolence; Dyssomnias; Nervous System Diseases; Mental Disorders; Sleep Wake Disorders; Sleepiness; Cataplexy; Narcolepsy

Condition Hierarchy (Ancestors)

Sleep Disorders, Intrinsic; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Centessa Pharmaceuticals

CONTACT

617-468-5770; ORX750trials@centessa.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2026
• First Posted: May 20, 2026
• Study Start: May 15, 2026
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: May 20, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share