A Study of ORX750 in Participants With Narcolepsy and Idiopathic Hypersomnia (CRYSTAL-1)

Centessa Pharmaceuticals

Status and phase: Enrolling; Phase 2

Conditions: Narcolepsy Type 2; Idiopathic Hypersomnia; Narcolepsy Type 1

Treatments: Drug: Placebo; Drug: ORX750

Study type: Interventional

Funder types: Industry

Identifiers

NCT06752668

ORX750-0201

2024-518929-15-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

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. 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.

Enrollment: 78 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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78 participants in 3 patient groups

Narcolepsy Type 1: ORX750 and Placebo

Experimental group

Treatment:

Drug: ORX750

Drug: Placebo

Narcolepsy Type 2: ORX750 and Placebo

Experimental group

Treatment:

Drug: ORX750

Drug: Placebo

Idiopathic Hypersomnia: ORX750 and Placebo

Experimental group

Treatment:

Drug: ORX750

Drug: Placebo

Sponsor of this trial

Lead Sponsor

Centessa Pharmaceuticals