A Study of ORX750 in Participants With Narcolepsy and Idiopathic Hypersomnia

NCT06752668 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: ORX750-02012024-518929-15-00
• Study Type: interventional
• Target: 248
• Locations: 5 countries
• Sites: 37

Brief Summary

Narcolepsy Type 1 (NT1), Narcolepsy Type 2 (NT2), and Idiopathic Hypersomnia (IH) 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.
• IH: People with IH feel tired during the day, even after sleeping a lot at night. They may sleep for long periods, take long naps, and find it hard to wake up. 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 (also known as ORX750) is designed to mimic the action of orexin. The purpose of this study is to see how safe and tolerable ORX750 is in NT1, NT2, and IH, and learn about what the drug does to the body. Another goal of the study is to see if ORX750 can help people with NT1, NT2, and IH feel less sleepy and make other symptoms better.

Conditions

Narcolepsy Type 1; Narcolepsy Type 2; Idiopathic Hypersomnia

Outcome Measures

Primary Outcomes (5)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs

  Up to Day 35

• Number of Participants With Abnormal Changes From Baseline in Laboratory Tests

  Up to Day 35

• Number of Participants With Abnormal Change From Baseline in Vital Signs

  Up to Day 35

• Number of Participants With Abnormal Change From Baseline in Electrocardiograms (ECG)

  Up to Day 35

• Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS)

  Up to Day 35

Secondary Outcomes (7)

• Cmax: Maximum Observed Plasma Concentration for ORX750

  Day 1, 15, 28

• Tmax: Time of Maximum Concentration for ORX750

  Day 1, 15, 28

• AUC0last: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for ORX750

  up to Day 28

• Cmax,ss: Maximum Observed Concentration at Steady State for ORX750

  Day 1, 15, 28

• AUCτ: Area Under the Concentration-time Curve During a Dosing Interval at Steady State for ORX750

  Day 1, 15, 28

Study Arms (3)

Narcolepsy Type 1: ORX750 and Placebo

EXPERIMENTAL

Drug: ORX750; Drug: Placebo

Narcolepsy Type 2: ORX750 and Placebo

EXPERIMENTAL

Drug: ORX750; Drug: Placebo

Idiopathic Hypersomnia: ORX750 and Placebo

EXPERIMENTAL

Drug: ORX750; Drug: Placebo

Interventions

ORX750 DRUG

ORX750 capsule.

Idiopathic Hypersomnia: ORX750 and Placebo; Narcolepsy Type 1: ORX750 and Placebo; Narcolepsy Type 2: ORX750 and Placebo

Placebo DRUG

ORX750 matching placebo capsule.

Idiopathic Hypersomnia: ORX750 and Placebo; Narcolepsy Type 1: ORX750 and Placebo; Narcolepsy Type 2: ORX750 and Placebo

Eligibility Criteria

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

You may qualify if:

• years of age
• BMI ≥17 and ≤37 kg/m2
• Meets the diagnostic criteria of Narcolepsy Type 1 (NT1), Type 2 (NT2) or Idiopathic Hypersomnia (IH) according to ICSD-3-TR criteria
• Is willing and able to discontinue all medications used for the treatment of narcolepsy or idiopathic hypersomnia
• Is willing and able to adhere to additional protocol requirements

You may not qualify if:

• A medical disorder other than NT1, NT2, or IH 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

Study Sites (37)

Auburn, Alabama

Auburn, Alabama, 36832, United States

RECRUITING

Chandler, Arizona

Chandler, Arizona, 85224, United States

RECRUITING

Scottsdale, Arizona

Scottsdale, Arizona, 85253, United States

RECRUITING

Long Beach, California

Long Beach, California, 90805, United States

RECRUITING

Santa Ana, California

Santa Ana, California, 92705, United States

RECRUITING

Brandon, Florida

Brandon, Florida, 33511, United States

RECRUITING

Miami, Florida

Miami, Florida, 33155, United States

RECRUITING

Miami, Florida

Miami, Florida, 33176, United States

RECRUITING

Orlando, FL

Orlando, Florida, 32807, United States

RECRUITING

Winter Park, Florida

Winter Park, Florida, 32789, United States

RECRUITING

Atlanta, Georgia

Atlanta, Georgia, 30281, United States

RECRUITING

Atlanta, Georgia

Atlanta, Georgia, 30328, United States

RECRUITING

Riverdale, Georgia

Riverdale, Georgia, 30274, United States

RECRUITING

New Orleans, Louisiana

New Orleans, Louisiana, 70127, United States

RECRUITING

Newton, Massachusetts

Newton, Massachusetts, 02459, United States

RECRUITING

Southfield, Michigan

Southfield, Michigan, 48075, United States

RECRUITING

Sterling Heights, Michigan

Sterling Heights, Michigan, 48314, United States

RECRUITING

Henderson, Nevada

Henderson, Nevada, 89052, United States

RECRUITING

Denver, North Carolina

Denver, North Carolina, 28037, United States

RECRUITING

Huntersville, North Carolina

Huntersville, North Carolina, 28078, United States

RECRUITING

Cincinnati, Ohio

Cincinnati, Ohio, 45245, United States

RECRUITING

Cleveland, OH

Cleveland, Ohio, 44106, United States

RECRUITING

Dublin, Ohio

Dublin, Ohio, 43017, United States

RECRUITING

Willow Grove, Pennsylvania

Willow Grove, Pennsylvania, 19090, United States

RECRUITING

Columbia, South Carolina

Columbia, South Carolina, 29201, United States

RECRUITING

North Charleston, South Carolina

North Charleston, South Carolina, 29406, United States

RECRUITING

Austin, Texas

Austin, Texas, 78731, United States

RECRUITING

El Paso, TX

El Paso, Texas, 79912, United States

RECRUITING

San Antonio, Texas

San Antonio, Texas, 78229, United States

RECRUITING

Toronto, Ontario

Toronto, Ontario, M5S 3A3, Canada

RECRUITING

Leon, France

Léon, Bordeaux, 33000, France

RECRUITING

Bologna, Italy

Bologna, 40139, Italy

RECRUITING

Pozzilli, Italy

Pozzilli, 86077, Italy

RECRUITING

Verona, Italy

Verona, 37134, Italy

RECRUITING

Madrid, Spain

Madrid, 28036, Spain

RECRUITING

Madrid, Spain

Madrid, 28043, Spain

RECRUITING

Vitoria-Gasteiz, Spain

Vitoria-Gasteiz, 01009, Spain

RECRUITING

MeSH Terms

Conditions

Idiopathic Hypersomnia

Condition Hierarchy (Ancestors)

Disorders of Excessive Somnolence; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders

Central Study Contacts

Centessa Pharmaceuticals

CONTACT

+1 617-468-5770; CRYSTAL-1@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: December 23, 2024
• First Posted: December 31, 2024
• Study Start: December 23, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (3); ES (3); FR (1); CA (1); US (29)