TAK-861 for Narcolepsy

No longer recruiting at 57 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called TAK-861 to determine its effectiveness in reducing excessive daytime sleepiness and unexpected muscle weakness (cataplexy) in individuals with narcolepsy. Participants will receive varying doses of the treatment or a placebo (a pill with no active medicine) for 12 weeks. The trial also examines how TAK-861 affects attention, quality of life, and daily activities. Individuals who frequently experience sudden muscle weakness episodes and have a specific diagnosis of narcolepsy with cataplexy may be suitable candidates for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

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.

Is there any evidence suggesting that TAK-861 is likely to be safe for humans?

Research has shown that TAK-861 is generally safe for humans. One study found that TAK-861, a drug that helps maintain wakefulness, effectively keeps people alert during the day. In trials, participants did not report major side effects, suggesting its safety. However, as with any treatment, some side effects might occur, so discussing these with the trial team is important. Overall, current evidence supports TAK-861's safety in treating narcolepsy symptoms. ^{1 2 3 4 5}

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

Unlike the standard treatments for narcolepsy, which often include stimulants like modafinil or sodium oxybate that work to promote wakefulness, TAK-861 offers a novel approach. TAK-861 is unique because it targets the orexin system, which plays a key role in regulating wakefulness and sleep. This new mechanism of action could potentially lead to improved wakefulness with fewer side effects compared to current options. Researchers are excited about TAK-861 because it could provide a more targeted and effective treatment for narcolepsy, addressing the root cause of the disorder rather than just managing symptoms.

What evidence suggests that TAK-861 could be an effective treatment for narcolepsy?

Research has shown that TAK-861 may help treat narcolepsy symptoms. In earlier studies, participants who took TAK-861 stayed awake more easily and felt less sleepy during the day. The medication also reduced the number of cataplexy attacks, which are sudden episodes of muscle weakness. In this trial, participants will receive either TAK-861 at one of two doses or a placebo. Compared to a placebo, TAK-861 improved attention and reduced brief, unintended sleep episodes known as microsleeps. These findings suggest that TAK-861 could effectively manage narcolepsy symptoms. ^{1 2 3 4 6}

Who Is on the Research Team?

Study Director

Principal Investigator

Takeda

Are You a Good Fit for This Trial?

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 am positive for a specific genetic marker or have low levels of a certain brain hormone.

I have been diagnosed with Narcolepsy Type 1.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. takeda.com takeda.com/newsroom/newsreleases/2025/takeda-orexin-data-oveporexton-phase-3-narcolepsy-world-sleep-2025/

Takeda Presents Orexin Data from Landmark Oveporexton ... Discover how Takeda's Oveporexton (TAK-861) Phase 3 studies reveal significant improvements in narcolepsy type 1 symptoms, marking a ...

2. neurology.org neurology.org/doi/10.1212/WNL.0000000000208433

Efficacy and Safety of TAK-861, an Oral Orexin Receptor 2 ... Compared with placebo, improvements from baseline to week 8 were achieved with TAK-861 doses in SOL-MWT (LS means change 12.5–25.4 vs −1.2 ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05687903

A Study of TAK-861 in Participants With Narcolepsy Type 1 This study will look at the effect of TAK-861 on improvement in narcolepsy symptoms, including excessive daytime sleepiness (EDS) and number of cataplexy ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40367374/

Oveporexton, an Oral Orexin Receptor 2-Selective Agonist, ... In this phase 2 trial involving participants with narcolepsy type 1, oveporexton significantly improved measures of wakefulness, sleepiness, ...

5. neurologylive.com neurologylive.com/view/investigational-therapy-tak-861-reduces-microsleeps-phase-2-trial-nt1

Investigational Therapy TAK-861 Reduces Microsleeps in ... TAK-861 significantly reduced microsleep rates and delayed microsleep onset in NT1 patients, demonstrating its potential as an effective ...

6. nature.com nature.com/articles/s41598-024-70594-1

TAK-861, a potent, orally available orexin receptor 2 ... Thus, TAK-861 has potential as an effective treatment for individuals with hypersomnia disorders including narcolepsy, potentially with a ...