ORX750 for Narcolepsy and Idiopathic Hypersomnia

(CRYSTAL-1 Trial)

Recruiting at 28 trial locations

Overseen By Centessa Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Centessa Pharmaceuticals (UK) Limited

Disqualifiers: Cardiovascular, Pulmonary, Neurological, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

96 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ORX750, designed to reduce daytime sleepiness in people with narcolepsy and idiopathic hypersomnia (IH). The trial evaluates the safety of ORX750 and its effects on these conditions, which cause excessive daytime sleepiness (EDS) and, in some cases, sudden muscle weakness (cataplexy). Participants will receive either ORX750 or a placebo (a pill with no active medication) for comparison. Individuals diagnosed with Narcolepsy Type 1, Narcolepsy Type 2, or IH who are willing to stop their current medications might be suitable for this study. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant advancements in treatment.

Will I have to stop taking my current medications?

Yes, you will need to stop taking all medications used for treating narcolepsy or idiopathic hypersomnia to participate in this trial.

Is there any evidence suggesting that ORX750 is likely to be safe for humans?

Research shows that ORX750 is a new treatment being tested for people with narcolepsy and idiopathic hypersomnia. Early studies have examined the safety of ORX750 in humans. Initial results suggest that most participants did not experience serious side effects, indicating the treatment is generally well-tolerated.

ORX750 is designed to mimic orexin, a brain protein that helps maintain wakefulness during the day. Although more research is needed, the current phase of testing suggests that ORX750 is promising in terms of safety. This stage of research typically checks for serious side effects and helps determine how the treatment affects the body.

For those considering joining a trial, this information may provide insight into the safety of ORX750. Always consult a healthcare provider to discuss any concerns or questions about participating in a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for narcolepsy and idiopathic hypersomnia?

Most treatments for narcolepsy and idiopathic hypersomnia typically focus on stimulating the central nervous system to reduce excessive daytime sleepiness. However, ORX750 works differently by targeting the orexin system, which plays a crucial role in regulating wakefulness and sleep. This new mechanism of action is what excites researchers, as it has the potential to address the root cause of these sleep disorders more directly than current stimulant-based therapies. Additionally, ORX750 may offer a more targeted approach with possibly fewer side effects compared to traditional treatments like modafinil or amphetamines.

What evidence suggests that ORX750 might be an effective treatment for narcolepsy and idiopathic hypersomnia?

Research has shown that ORX750, a new treatment under study in this trial, appears promising for individuals with narcolepsy and idiopathic hypersomnia. In earlier studies, ORX750 helped participants stay awake longer during the day. Specifically, it increased the time it took for participants to fall asleep by more than 10 minutes compared to a placebo. Additionally, ORX750 was well tolerated, with most participants experiencing no major side effects. This trial will evaluate ORX750 in separate arms for narcolepsy type 1, narcolepsy type 2, and idiopathic hypersomnia. These early results suggest that ORX750 could help reduce excessive daytime sleepiness in these conditions. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with a BMI between 17 and 37 who have narcolepsy or idiopathic hypersomnia. Participants must be able to follow the study rules and stop taking their current narcolepsy or hypersomnia meds. They can't join if they have serious health issues like heart, lung, liver diseases, or other conditions causing excessive sleepiness.

Inclusion Criteria

BMI ≥17 and ≤37 kg/m2

Is willing and able to adhere to additional protocol requirements

I can stop my narcolepsy or hypersomnia medication.

Exclusion Criteria

I have a serious heart, lung, liver, kidney, blood, cancer, hormone, nerve, or mental health condition.

I have a condition causing excessive daytime sleepiness not diagnosed as NT1, NT2, or IH.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ORX750 or placebo to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics

6 weeks

Regular visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ORX750

Trial Overview

The trial is testing ORX750 against a placebo to see how safe it is and how it affects the body (PK/PD) in people with narcolepsy or idiopathic hypersomnia. It aims to understand if ORX750 can help manage symptoms better than an inactive substance.

How Is the Trial Designed?

Group I: Narcolepsy Type 2: ORX750 and Placebo Experimental Treatment 2 Interventions

Group II: Narcolepsy Type 1: ORX750 and Placebo Experimental Treatment 2 Interventions

Group III: Idiopathic Hypersomnia: ORX750 and Placebo Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

Centessa Pharmaceuticals (UK) Limited

Lead Sponsor

Trials

2

Recruited

100+

Published Research Related to This Trial

Patients with idiopathic hypersomnia (IH) experience more consolidated nocturnal sleep and report feeling more refreshed after naps compared to those with narcoleptic syndrome (NLS), indicating differences in sleep quality between the two conditions.

The onset of excessive daytime sleepiness in IH is often linked to familial factors or viral illnesses, while key variables like the number of awakenings during sleep and changes in sleepiness since onset help distinguish IH from NLS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of idiopathic hypersomnia and narcolepsy-cataplexy using self report measures and sleep diary data. Bruck, D., Parkes, JD.[2019]

Narcolepsy is a distinct sleep disorder characterized by excessive daytime sleepiness and cataplexy, which involves sudden loss of muscle tone and can lead to sleep paralysis and hallucinations.

Treatment for narcolepsy includes lifestyle adjustments and medications, such as stimulants for daytime sleepiness and tricyclic drugs to manage cataplexy, highlighting the need for a comprehensive approach to care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Narcoleptic syndrome]. Hess, CW.[2015]

Idiopathic hypersomnia can present in two forms: a polysymptomatic form with excessive daytime sleepiness and long nocturnal sleep, and a monosymptomatic form characterized only by excessive daytime sleepiness.

Diagnosis can be challenging due to the potential for overdiagnosis and the need to exclude other disorders; treatment typically involves stimulants, which may be less effective and well tolerated compared to treatments for narcolepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Idiopathic hypersomnia. Billiard, M.[2019]

Narcolepsy affects a small percentage of the population and is linked to genetic factors and the loss of hypocretin-producing neurons, suggesting an autoimmune component that may be triggered by environmental factors.

Current treatments like sodium oxybate and modafinil effectively manage symptoms such as excessive daytime sleepiness and cataplexy, while emerging therapies focus on both non-hypocretin-based and hypocretin-based approaches to improve outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New developments in the management of narcolepsy. Abad, VC., Guilleminault, C.[2020]

Modafinil is recommended as the first-line treatment for excessive daytime sleepiness (EDS) in central hypersomnias like narcolepsy and idiopathic hypersomnia, with other stimulants available for patients who do not respond to it.

New therapies are being developed that aim to restore hypocretin levels or address the autoimmune processes involved in narcolepsy, which could lead to more effective treatments in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

French consensus. Management of patients with hypersomnia: Which strategy? Lopez, R., Arnulf, I., Drouot, X., et al.[2017]

Citations

1.

neurology.org

neurology.org/doi/10.1212/WNL.0000000000209036

Phase 1 Clinical Data with Orexin Receptor 2 (OX2R) ...

Conclusions: Results support that ORX750 was well tolerated across the evaluated dose range, and clinically meaningful and statistically significant ...

2.

investors.centessa.com

investors.centessa.com/news-releases/news-release-details/centessa-pharmaceuticals-reports-financial-results-third-0

Release Details

In the 4.0 mg cohort (n=10), ORX750 achieved a >10 minute change from baseline in mean sleep latency compared with placebo on the MWT at Week 2 ...

3.

academic.oup.com

academic.oup.com/sleep/article-abstract/48/Supplement_1/A373/8134737

0861 A Phase 2a, Double-blind, Placebo-controlled Study of ...

This study will evaluate the safety, tolerability, efficacy, and PK of multiple doses of ORX750 for the first time in patients with NT1, NT2, ...

4.

investors.centessa.com

investors.centessa.com/static-files/36250139-54c5-4287-ab84-832eef25f705

CRYSTAL-1 Study Design

Narcolepsy types 1 (NT1) and 2 (NT2) and idiopathic hypersomnia (IH) are rare, debilitating central disorders of hypersomnolence ...

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06752668

NCT06752668 | A Study of ORX750 in Participants With ...

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 ...

6.

academic.oup.com

academic.oup.com/sleep/article/48/Supplement_1/A373/8134737

0861 A Phase 2a, Double-blind, Placebo-controlled Study of ...

This study will evaluate the safety, tolerability, efficacy, and PK of multiple doses of ORX750 for the first time in patients with NT1, NT2, and IH.

7.

clinicaltrials.eu

clinicaltrials.eu/trial/study-on-the-safety-and-effects-of-orx750-for-patients-with-narcolepsy-and-idiopathic-hypersomnia/

Study on the Safety and Effects of ORX750 for Patients ...

This study investigates the safety and effects of the drug ORX750 on patients suffering from sleep disorders, specifically narcolepsy and ...