Narcolepsy Type 1Phase 2CRYSTAL-1NCT06752668
A Study of ORX750 in Participants With Narcolepsy and Idiopathic Hypersomnia
A Phase 2 study testing ORX750 in people with Narcolepsy Type 1 and Narcolepsy Type 2, run by Centessa Pharmaceuticals (UK) Limited at 37 sites in 5 countries.
Trial 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]). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Narcolepsy Type 1, Narcolepsy Type 2, Idiopathic Hypersomnia
- What is being tested?
- ORX750
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 248 participants
- Where
- 37 sitesin 5 countries
- Study dates
- 23 Dec 2024to Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
37 sites in 5 countries. Contact the study team or a site near you to ask about taking part.
37 sites in 5 countries
United States29 sites, 29 recruiting
- Recruiting
Atlanta, Georgia
Atlanta, Georgia, 30281
- Recruiting
Atlanta, Georgia
Atlanta, Georgia, 30328
- Recruiting
Auburn, Alabama
Auburn, Alabama, 36832
- Recruiting
Austin, Texas
Austin, Texas, 78731
- Recruiting
Brandon, Florida
Brandon, Florida, 33511
- Recruiting
Chandler, Arizona
Chandler, Arizona, 85224
- Recruiting
Cincinnati, Ohio
Cincinnati, Ohio, 45245
- Recruiting
Cleveland, OH
Cleveland, Ohio, 44106
- Recruiting
Columbia, South Carolina
Columbia, South Carolina, 29201
- Recruiting
Denver, North Carolina
Denver, North Carolina, 28037
- Recruiting
Dublin, Ohio
Dublin, Ohio, 43017
- Recruiting
El Paso, TX
El Paso, Texas, 79912
- Recruiting
Henderson, Nevada
Henderson, Nevada, 89052
- Recruiting
Huntersville, North Carolina
Huntersville, North Carolina, 28078
- Recruiting
Long Beach, California
Long Beach, California, 90805
- Recruiting
Miami, Florida
Miami, Florida, 33155
- Recruiting
Miami, Florida
Miami, Florida, 33176
- Recruiting
New Orleans, Louisiana
New Orleans, Louisiana, 70127
- Recruiting
Newton, Massachusetts
Newton, Massachusetts, 02459
- Recruiting
North Charleston, South Carolina
North Charleston, South Carolina, 29406
- Recruiting
Orlando, FL
Orlando, Florida, 32807
- Recruiting
Riverdale, Georgia
Riverdale, Georgia, 30274
- Recruiting
San Antonio, Texas
San Antonio, Texas, 78229
- Recruiting
Santa Ana, California
Santa Ana, California, 92705
- Recruiting
Scottsdale, Arizona
Scottsdale, Arizona, 85253
- Recruiting
Southfield, Michigan
Southfield, Michigan, 48075
- Recruiting
Sterling Heights, Michigan
Sterling Heights, Michigan, 48314
- Recruiting
Willow Grove, Pennsylvania
Willow Grove, Pennsylvania, 19090
- Recruiting
Winter Park, Florida
Winter Park, Florida, 32789
Italy3 sites, 3 recruiting
- Recruiting
Bologna, Italy
Bologna, 40139
- Recruiting
Pozzilli, Italy
Pozzilli, 86077
- Recruiting
Verona, Italy
Verona, 37134
Spain3 sites, 3 recruiting
- Recruiting
Madrid, Spain
Madrid, 28036
- Recruiting
Madrid, Spain
Madrid, 28043
- Recruiting
Vitoria-Gasteiz, Spain
Vitoria-Gasteiz, 01009
Canada1 site, 1 recruiting
- Recruiting
Toronto, Ontario
Toronto, Ontario, M5S 3A3
About this study
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)
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:
Read more
- 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
- Being tested
- ORX750, Placebo
- Medical subject headings
- Idiopathic Hypersomnia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ORX750Drug
ORX750 capsule.
PlaceboDrug
ORX750 matching placebo capsule.
| Study group | Role | What they receive |
|---|---|---|
| Narcolepsy Type 1: ORX750 and Placebo | Experimental | Not described Receives: Drug: ORX750; Drug: Placebo |
| Narcolepsy Type 2: ORX750 and Placebo | Experimental | Not described Receives: Drug: ORX750; Drug: Placebo |
| Idiopathic Hypersomnia: ORX750 and Placebo | Experimental | Not described Receives: Drug: ORX750; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
Measured: Up to Day 35
Number of Participants With Abnormal Changes From Baseline in Laboratory Tests
Measured: Up to Day 35
Number of Participants With Abnormal Change From Baseline in Vital Signs
Measured: Up to Day 35
Number of Participants With Abnormal Change From Baseline in Electrocardiograms (ECG)
Measured: Up to Day 35
Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS)
Measured: Up to Day 35
Secondary outcomes (7)
Cmax: Maximum Observed Plasma Concentration for ORX750
Measured: Day 1, 15, 28
Tmax: Time of Maximum Concentration for ORX750
Measured: 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
Measured: up to Day 28
Cmax,ss: Maximum Observed Concentration at Steady State for ORX750
Measured: Day 1, 15, 28
AUCτ: Area Under the Concentration-time Curve During a Dosing Interval at Steady State for ORX750
Measured: Day 1, 15, 28
Mean sleep latency (average of the first 4 trials) in the Maintenance of Wakefulness Test (MWT) for ORX750 versus placebo.
Mean sleep latency is determined by averaging the time to falling asleep across trials
Measured: Baseline up to Day 28
Change From Baseline in Epworth Sleepiness Scale (ESS)
Measured: Baseline up to Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Dec 2024
- Study start23 Dec 2024
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Narcolepsy Type 1Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 248 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centessa Pharmaceuticals (UK) Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06752668
- Sponsor's protocol ID
- ORX750-0201
- Other IDs
- 2024-518929-15-00
- Acronym
- CRYSTAL-1
- Status last verified
- Apr 2026
- First submitted
- 23 Dec 2024
- Last updated
- 27 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT06752668
- Acronym / sponsor ID
- CRYSTAL-1 / ORX750-0201
- Conditions
- Narcolepsy Type 1, Narcolepsy Type 2, Idiopathic Hypersomnia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 248 participants (estimated)
- Lead sponsor
- Centessa Pharmaceuticals (UK) LimitedIndustry (pharma, biotech, devices)
- Study start
- 23 Dec 2024 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 31 Dec 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (2 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ORX750ORX750 capsule. | Drug | Idiopathic Hypersomnia: ORX750 and Placebo, Narcolepsy Type 1: ORX750 and Placebo, Narcolepsy Type 2: ORX750 and Placebo |
| PlaceboORX750 matching placebo capsule. | Drug | Idiopathic Hypersomnia: ORX750 and Placebo, Narcolepsy Type 1: ORX750 and Placebo, Narcolepsy Type 2: ORX750 and Placebo |
Primary outcome
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
7 secondary outcomes
Cmax: Maximum Observed Plasma Concentration for ORX750
Time frame: Day 1, 15, 28
Tmax: Time of Maximum Concentration for ORX750
Time frame: 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
Time frame: up to Day 28
Cmax,ss: Maximum Observed Concentration at Steady State for ORX750
Time frame: Day 1, 15, 28
AUCτ: Area Under the Concentration-time Curve During a Dosing Interval at Steady State for ORX750
Time frame: Day 1, 15, 28
Mean sleep latency (average of the first 4 trials) in the Maintenance of Wakefulness Test (MWT) for ORX750 versus placebo.
Time frame: Baseline up to Day 28
Change From Baseline in Epworth Sleepiness Scale (ESS)
Time frame: Baseline up to Day 28
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2026.
- Individual participant dataSharing planned: No
Related trials for Narcolepsy Type 1
RecruitingPhase 2/3
A Study of TAK-360 in People With Narcolepsy or Idiopathic Hypersomnia
Idiopathic Hypersomnia, Narcolepsy Type 1
RecruitingPhase 2/3
A Study to Investigate the Effects of Cleminorexton Compared With Placebo in the Treatment of Participants With Central Disorders of Hypersomnolence
Narcolepsy Type 1, Narcolepsy Type 2
Active, not recruitingObservational study
Epidemiology of Narcolepsy Type 1 and Type 2 in Spain
Narcolepsy Type 1, Narcolepsy Type 2
Active, not recruitingPhase 3
A Trial of TAK-861 for the Treatment of Narcolepsy With Cataplexy
Narcolepsy Type 1 (NT1), Narcolepsy With Cataplexy
Not yet recruitingObservational study
A Study About Treatment Use in Adults With Narcolepsy Type 1 (NT1) in Europe and Canada
Narcolepsy Type 1
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
37 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ORX750 in people with Narcolepsy Type 1 and Narcolepsy Type 2, run by Centessa Pharmaceuticals (UK) Limited at 37 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 37 sites in United States, Italy, Spain, Canada, France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Centessa Pharmaceuticals (+1 617-468-5770, CRYSTAL-1@centessa.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs (time frame: Up to Day 35). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2026.