TAK-861 for Narcolepsy

Recruiting at 52 trial locations

Overseen By Takeda Contact

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Takeda

Disqualifiers: Heart disease, Cancer, Epilepsy, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

168 Participants Needed

Trial Summary

What is the purpose of this trial?

The main aim of this study is to learn how effective TAK-861 is in improving excessive sleepiness during the day (called excessive daytime sleepiness or EDS) after 3 months of treatment. Other aims are to learn how effective TAK-861 is in lowering the number of sudden, unexpected attacks of muscle weakness while staying conscious (cataplexy) in a week; to learn the effect TAK-861 has on participants' ability to maintain attention, participant's overall quality of life, the spectrum of narcolepsy symptoms, and daily life functions; and to learn about the safety of TAK-861.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

How is the drug TAK-861 different from other narcolepsy treatments?

TAK-861 is unique because it is an orexin 2 receptor agonist, which means it specifically targets and activates receptors in the brain that help regulate wakefulness, potentially offering a more targeted approach to treating narcolepsy compared to other treatments that may have broader effects or more side effects. ^{1 2 3 4 5}

Research Team

Study Director

Principal Investigator

Takeda

Eligibility Criteria

This trial is for individuals with Narcolepsy Type 1, who often feel extremely sleepy during the day or have sudden muscle weakness. Participants should be looking to improve these symptoms and their overall quality of life.

Inclusion Criteria

Participant has a body mass index (BMI) within the range 18 to 40 kg/m^2

I have been diagnosed with Narcolepsy Type 1.

I experience 4 or more episodes of sudden muscle weakness a week.

Exclusion Criteria

I have had cancer within the last 5 years.

Participant has a clinically significant history of head injury or trauma

I have had a stroke, mini-stroke, brain aneurysm, or blood vessel malformation in the last 5 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TAK-861 or placebo tablets orally for 12 weeks

12 weeks

Regular visits as per study protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• TAK-861

Trial Overview The study tests TAK-861's effectiveness in reducing daytime sleepiness and muscle weakness episodes over three months. It also examines attention span, life quality, symptom range, and daily function compared to a placebo.

Participant Groups

Group I: TAK-861 Dose 2 Experimental Treatment 1 Intervention

Participants will receive TAK-861 tablets at dose 2, orally, for 12 weeks.

Group II: TAK-861 Dose 1 Experimental Treatment 1 Intervention

Participants will receive TAK-861 tablets at dose 1, orally, for 12 weeks.

Group III: Placebo Placebo Group 1 Intervention

Participants will receive TAK-861-matching placebo tablets, orally, for 12 weeks.

Who Is Running the Clinical Trial?

Takeda

Lead Sponsor

Trials

1,255

Recruited

4,219,000+

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

Findings from Research

Danavorexton (TAK-925) is a promising new treatment for narcolepsy type 1 (NT1) that activates orexin 2 receptors, showing potential to improve wakefulness and reduce sleep fragmentation in preclinical models.

In tests on mice with NT1, danavorexton not only promoted wakefulness but also helped control body weight gain, suggesting it may address multiple symptoms of the disorder effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Danavorexton, a selective orexin 2 receptor agonist, provides a symptomatic improvement in a narcolepsy mouse model. Ishikawa, T., Hara, H., Kawano, A., et al.[2022]

In a study using narcoleptic mice, two HCRTR2 agonists, TAK-925 and ARN-776, were found to significantly promote wakefulness and eliminate cataplexy, a common symptom of narcolepsy, especially at higher doses.

Both compounds increased gamma EEG activity and gross motor activity, indicating their potential as effective treatments for narcolepsy, although they did not cause a rebound in NREM sleep, suggesting a targeted mechanism of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the efficacy of the hypocretin/orexin receptor agonists TAK-925 and ARN-776 in narcoleptic orexin/tTA; TetO-DTA mice. Sun, Y., Ranjan, A., Tisdale, R., et al.[2023]

The TAAR1 agonist RO5256390 significantly reduced rapid eye movement (REM) sleep and mitigated cataplexy in mouse models of narcolepsy, indicating its potential as a new treatment pathway for this disorder.

Both the full agonist RO5256390 and the partial agonist RO5263397 promoted wakefulness and reduced cataplexy episodes, suggesting that targeting TAAR1 could effectively address key symptoms of narcolepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trace Amine-Associated Receptor 1 Agonists as Narcolepsy Therapeutics. Black, SW., Schwartz, MD., Chen, TM., et al.[2018]

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]

TAK-925 is a selective agonist for the orexin 2 receptor (OX2R) that effectively promotes wakefulness in mice, indicating its potential as a treatment for narcolepsy and related sleep disorders.

The compound was developed through optimization of an earlier discovery and shows promise due to its ability to penetrate the brain and enhance wakefulness during sleep phases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery of TAK-925 as a Potent, Selective, and Brain-Penetrant Orexin 2 Receptor Agonist. Fujimoto, T., Rikimaru, K., Fukuda, K., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Danavorexton, a selective orexin 2 receptor agonist, provides a symptomatic improvement in a narcolepsy mouse model. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Evaluation of the efficacy of the hypocretin/orexin receptor agonists TAK-925 and ARN-776 in narcoleptic orexin/tTA; TetO-DTA mice. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Trace Amine-Associated Receptor 1 Agonists as Narcolepsy Therapeutics. [2018]

4. New Zealand pubmed.ncbi.nlm.nih.gov

New developments in the management of narcolepsy. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Discovery of TAK-925 as a Potent, Selective, and Brain-Penetrant Orexin 2 Receptor Agonist. [2022]