ORX750 for Narcolepsy | Idiopathic hypersomnia

Inclusion criteria

• {"criterion_text":"- All Participants: •\tParticipants with narcolepsy (NT1 or NT2) or IH who have completed the full treatment period in Study ORX750-0201.\n- All Participants: •\tParticipants must be able and willing to participate in all scheduled evaluations and procedures per protocol and must agree to be available to complete all study measurements and comply with study restrictions.\n- All Participants: •\tMale and female participants must comply with contraception requirements described in the protocol.\n- Returning Participants Only: o\t18-65 years of age\n- Returning Participants Only: o\tBMI ≥17.0 and ≤37 kg/m2\n- Returning Participants Only: o\tEstimated glomerular filtration rate ≥60 mL/min/1.73 m2\n- Returning Participants Only: o\tIs willing and able to discontinue all medications used for the treatment of narcolepsy or idiopathic hypersomnia\n- Returning Participants Only: o\tIs willing and able to adhere to additional protocol requirements\n- Rollover Participants Only: o\tEach participant must provide written informed consent by the final treatment visit (Day 42) in Study ORX750-0201, before the performance of any study-related procedures in the LTE study"}

Exclusion criteria

• {"criterion_text":"- Returning Participants Only: •\tParticipant has a medical condition(s) other than NT1, NT2, or IH for which excluded medications should not be discontinued.\n- Returning Participants Only: •\tParticipant has participated in a study with an investigational drug other than ORX750 within the previous 30 days or within 5 half-lives of the investigational drug administration, whichever is longer, calculated from the last dose of the investigational drug or any AE related to the prior study to the screening day.\n- Returning Participants Only: •\tPresence of significant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, hematological, malignancy, endocrine, neurological or psychiatric disease.\n- Rollover Participants Only: o\tDevelopment of any new disease/disorder that in the opinion of the investigator would make the participant unable to continue the study."}

Primary endpoints

• {"endpoint_text":"- Incidence, severity, and causal relationship of treatment emergent adverse events (TEAEs), including serious TEAEs","definition_or_measurement_approach":"Incidence, severity, and causal relationship of treatment emergent adverse events (TEAEs), including serious TEAEs"}
• {"endpoint_text":"- Changes from baseline in laboratory tests, including biochemistry, hematology, and urinalysis","definition_or_measurement_approach":"Changes from baseline in laboratory tests, including biochemistry, hematology, and urinalysis"}
• {"endpoint_text":"- Changes from baselinea in vital signs and weight","definition_or_measurement_approach":"Changes from baseline in vital signs and weight"}
• {"endpoint_text":"- Changes from baseline in 12-lead electrocardiograms (ECGs)","definition_or_measurement_approach":"Changes from baseline in 12-lead electrocardiograms (ECGs)"}
• {"endpoint_text":"- Columbia-Suicide Severity Rating Scale (C-SSRS) scores","definition_or_measurement_approach":"Assessment using the Columbia-Suicide Severity Rating Scale (C-SSRS) scores"}

Secondary endpoints

• {"endpoint_text":"- PK: - Predose and post dose PK concentrations of ORX750 - Other PK parameters as appropriate","definition_or_measurement_approach":"Predose and post-dose pharmacokinetic concentrations of ORX750 and other PK parameters as appropriate"}
• {"endpoint_text":"- Efficacy: o\tMean sleep latency (changes from baseline to Day 63) in the MWT (average of the first 4 trials) o Subjective daytime sleepiness (changes from baseline to specified post dose timepoints) using the ESS","definition_or_measurement_approach":"Mean sleep latency measured by the Maintenance of Wakefulness Test (MWT; average of first 4 trials) change from baseline to Day 63; subjective daytime sleepiness measured by the Epworth Sleepiness Scale (ESS) change from baseline at specified post-dose timepoints"}

Methods

• Site-based recruitment via participating hospitals/clinics in France, Italy and Spain (K1 Recruitment arrangements documents referenced).
• Vendor-hosted recruitment portal and site training/education developed and hosted by Neonstone Limited (vendor developing and hosting site training, education, and recruitment portal).
• Patient brochures and visit flowcharts (K2 recruitment materials) in ES/FR/IT.
• PatientGo app materials and associated information (PatientGO EULA, privacy policy) referenced for participant information and engagement.

France

Earliest CTIS Part Ii Submission Date

02-02-2026

Latest Decision Or Authorization Date

17-03-2026

Processing Time Days

43

Number Of Sites

2

Number Of Participants

15

Spain

Earliest CTIS Part Ii Submission Date

06-02-2026

Latest Decision Or Authorization Date

17-03-2026

Processing Time Days

40

Number Of Sites

3

Number Of Participants

20

Italy

Earliest CTIS Part Ii Submission Date

31-10-2025

Latest Decision Or Authorization Date

17-03-2026

Processing Time Days

137

Number Of Sites

3

Number Of Participants

20

Primary sponsor

Full Name

Centessa Pharmaceuticals UK Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

United Kingdom

Contract research organisations

Name

Syneos Health UK Limited

Responsibilities

codes: 1,10,11,12,13,2,3,5,6,7

Name

Neonstone Limited

Responsibilities

15: Vendor developing and hosting site training, education, and recruitment portal

Name

Millmount Healthcare Limited

Responsibilities

14; 15: Package and label, QP Release

Name

PCI Pharma Services Germany GmbH

Responsibilities

14; 15: Package and label, QP Release

Name

Clinilabs LLC

Responsibilities

15: Central Polysomnography and MWT scoring

Name

Celerion Inc.

Responsibilities

15: PK analysis; 4

Name

Labcorp Central Laboratory Services SARL

Responsibilities

4

Name

Cambridge Cognition Limited

Responsibilities

15: Cognitive Assessment Vendor for collection of PerfRO data

Name

CliniChain B.V.

Responsibilities

15: Supply of Equipment / devices

Name

Eresearchtechnology Inc.

Responsibilities

15: Central ECG reading

Name

Fortrea Inc.

Responsibilities

8

Third parties

• {"country":"United Kingdom","full_name":"Syneos Health UK Limited","duties_or_roles":"codes: 1,10,11,12,13,2,3,5,6,7","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Millmount Healthcare Limited","duties_or_roles":"14; 15: Package and label, QP Release","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Cambridge Cognition Limited","duties_or_roles":"15: Cognitive Assessment Vendor for collection of PerfRO data","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Clinilabs LLC","duties_or_roles":"15: Central Polysomnography and MWT scoring","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"PCI Pharma Services Germany GmbH","duties_or_roles":"14; 15: Package and label, QP Release","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Celerion Inc.","duties_or_roles":"15: PK analysis; 4","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"CliniChain B.V.","duties_or_roles":"15: Supply of Equipment / devices","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Neonstone Limited","duties_or_roles":"15: Vendor developing and hosting site training, education, and recruitment portal","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"15: Central ECG reading","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"8","organisation_type":"Pharmaceutical company"}