Recruiting

Phase 2

ORX750A Study of ORX750 in Participants With Narcolepsy and Idiopathic Hypersomnia

Sponsor:

Centessa Pharmaceuticals (UK) Limited

Code:

NCT06752668

Conditions

Narcolepsy Type 1

Narcolepsy Type 2

Idiopathic Hypersomnia

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

Interventions

ORX750

Placebo

Study Details

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

Study ID

NCT06752668

Start date

Dec 23, 2024

Status verified date

Apr, 2026

Completion date

Dec, 2026

Anticipated

Primary completion date

Dec, 2026

Anticipated

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

Inclusion Criteria:

18-65 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

Exclusion Criteria:

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

Study Design

Enrollment

248 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Narcolepsy Type 1: ORX750 and Placebo

experimental: Narcolepsy Type 2: ORX750 and Placebo

experimental: Idiopathic Hypersomnia: ORX750 and Placebo

Interventions

ORX750

ORX750 capsule.

Placebo

ORX750 matching placebo capsule.

Primary outcome measure

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs [ Time Frame: Up to Day 35 ]
Number of Participants With Abnormal Changes From Baseline in Laboratory Tests [ Time Frame: Up to Day 35 ]
Number of Participants With Abnormal Change From Baseline in Vital Signs [ Time Frame: Up to Day 35 ]
Number of Participants With Abnormal Change From Baseline in Electrocardiograms (ECG) [ Time Frame: Up to Day 35 ]
Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Up to Day 35 ]

Central Contacts and Locations

Central contacts

Centessa Pharmaceuticals

+1 617-468-5770 CRYSTAL-1@centessa.com

Locations

Auburn, Alabama

Recruiting

Auburn, Alabama, United States, 36832

Chandler, Arizona

Recruiting

Chandler, Arizona, United States, 85224

Scottsdale, Arizona

Recruiting

Scottsdale, Arizona, United States, 85253

Long Beach, California

Recruiting

Long Beach, California, United States, 90805

Santa Ana, California

Recruiting

Santa Ana, California, United States, 92705

Brandon, Florida

Recruiting

Brandon, Florida, United States, 33511

Miami, Florida

Recruiting

Miami, Florida, United States, 33155

Miami, Florida

Recruiting

Miami, Florida, United States, 33176

Orlando, FL

Recruiting

Orlando, Florida, United States, 32807

Winter Park, Florida

Recruiting

Winter Park, Florida, United States, 32789

Atlanta, Georgia

Recruiting

Atlanta, Georgia, United States, 30281

Atlanta, Georgia

Recruiting

Atlanta, Georgia, United States, 30328

Riverdale, Georgia

Recruiting

Riverdale, Georgia, United States, 30274

New Orleans, Louisiana

Recruiting

New Orleans, Louisiana, United States, 70127

Newton, Massachusetts

Recruiting

Newton, Massachusetts, United States, 02459

Southfield, Michigan

Recruiting

Southfield, Michigan, United States, 48075

Sterling Heights, Michigan

Recruiting

Sterling Heights, Michigan, United States, 48314

Henderson, Nevada

Recruiting

Henderson, Nevada, United States, 89052

Denver, North Carolina

Recruiting

Denver, North Carolina, United States, 28037

Huntersville, North Carolina

Recruiting

Huntersville, North Carolina, United States, 28078

Cincinnati, Ohio

Recruiting

Cincinnati, Ohio, United States, 45245

Cleveland, OH

Recruiting

Cleveland, Ohio, United States, 44106

Dublin, Ohio

Recruiting

Dublin, Ohio, United States, 43017

Willow Grove, Pennsylvania

Recruiting

Willow Grove, Pennsylvania, United States, 19090

Columbia, South Carolina

Recruiting

Columbia, South Carolina, United States, 29201

North Charleston, South Carolina

Recruiting

North Charleston, South Carolina, United States, 29406

Austin, Texas

Recruiting

Austin, Texas, United States, 78731

El Paso, TX

Recruiting

El Paso, Texas, United States, 79912

San Antonio, Texas

Recruiting

San Antonio, Texas, United States, 78229

Toronto, Ontario

Recruiting

Toronto, Ontario, Canada, M5S 3A3

More Information

Sponsor

Centessa Pharmaceuticals (UK) Limited

Last update posted

Apr 27, 2026

Last verified

Apr, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-10. This information was provided to ClinicalTrials.gov by Centessa Pharmaceuticals (UK) Limited on 2026-04-27. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.