Clinical trial NCT06752668: A Study of ORX750 in Participants With Narcolepsy and Idiopathic Hypersomnia
Official title: A Phase 2a, Randomized, Double-blind, Placebo-controlled Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ORX750 in Subjects With Narcolepsy and Idiopathic Hypersomnia (CRYSTAL-1)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Narcolepsy Type 1
Narcolepsy Type 2
Idiopathic Hypersomnia
Lead sponsor: Centessa Pharmaceuticals plc
Sponsor class: INDUSTRY
First posted: 2024-12-31
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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. 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
timeFrame: Up to Day 49
measure: Number of Participants With Abnormal Changes From Baseline in Laboratory Tests
timeFrame: Up to Day 49
measure: Number of Participants With Abnormal Change From Baseline in Vital Signs
timeFrame: Up to Day 49
measure: Number of Participants With Abnormal Change From Baseline in Electrocardiograms (ECG)
timeFrame: Up to Day 49
measure: Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Up to Day 49
Secondary outcomes:
measure: Cmax: Maximum Observed Plasma Concentration for ORX750
timeFrame: Day 1
measure: Tmax: Time of Maximum Concentration for ORX750
timeFrame: Days 1, 14 and 28
measure: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for ORX750
timeFrame: Day 1
measure: Cmax,ss: Maximum Observed Concentration at Steady State for ORX750
timeFrame: Days 14 and 28
measure: AUCτ: Area Under the Concentration-time Curve During a Dosing Interval at Steady State for ORX750
timeFrame: Days 14 and 28
measure: Mean sleep latency (average of the first 4 trials) in the Maintenance of Wakefulness Test (MWT) for ORX750 versus placebo.
timeFrame: Baseline up to Day 42
measure: Change From Baseline in Epworth Sleepiness Scale (ESS)
timeFrame: Baseline up to Day 41
Other outcomes:
Locations:
city: Auburn
country: United States
facility: Auburn, Alabama
state: Alabama
city: Chandler
country: United States
facility: Chandler, Arizona
state: Arizona
city: Scottsdale
country: United States
facility: Scottsdale, Arizona
state: Arizona
city: Long Beach
country: United States
facility: Long Beach, California
state: California
city: Santa Ana
country: United States
facility: Santa Ana, California
state: California
city: Brandon
country: United States
facility: Brandon, Florida
state: Florida
city: Miami
country: United States
facility: Miami, Florida
state: Florida
city: Miami
country: United States
facility: Miami, Florida
state: Florida
city: Winter Park
country: United States
facility: Winter Park, Florida
state: Florida
city: Atlanta
country: United States
facility: Atlanta, Georgia
state: Georgia
city: Atlanta
country: United States
facility: Atlanta, Georgia
state: Georgia
city: New Orleans
country: United States
facility: New Orleans, Louisiana
state: Louisiana
city: Newton
country: United States
facility: Newton, Massachusetts
state: Massachusetts
city: Sterling Heights
country: United States
facility: Sterling Heights, Michigan
state: Michigan
city: Henderson
country: United States
facility: Henderson, Nevada
state: Nevada
city: Denver
country: United States
facility: Denver, North Carolina
state: North Carolina
city: Huntersville
country: United States
facility: Huntersville, North Carolina
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati, Ohio
state: Ohio
city: Dublin
country: United States
facility: Dublin, Ohio
state: Ohio
city: Willow Grove
country: United States
facility: Willow Grove, Pennsylvania
state: Pennsylvania
city: Columbia
country: United States
facility: Columbia, South Carolina
state: South Carolina
city: North Charleston
country: United States
facility: North Charleston, South Carolina
state: South Carolina
city: Austin
country: United States
facility: Austin, Texas
state: Texas
city: San Antonio
country: United States
facility: San Antonio, Texas
state: Texas
city: Toronto
country: Canada
facility: Toronto, Ontario
state: Ontario
Study officials:
References: