TAK-861 for Narcolepsy

Recruiting at 64 trial locations

Overseen By Takeda Contact

Age: Any Age

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Takeda

Must be taking: TAK-861

Must not be taking: Antidepressants, Anticonvulsants

Disqualifiers: Suicide risk, Liver issues, 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: 1

Duration: Up to 5 years

500 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing TAK-861, a new drug, on people with type 1 and type 2 narcolepsy. The goal is to see if it can help reduce excessive daytime sleepiness and sudden muscle weakness. The study will involve up to 160 participants from previous studies and will last about two years.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude participants who need to take certain medications for conditions like anxiety, depression, heart disease, or significant liver, lung, or kidney disease.

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 people with narcolepsy who have already taken TAK-861 in earlier studies without serious side effects. They shouldn't have other sleep disorders, major depression recently, digestive issues affecting drug absorption, seizures, significant heart or liver diseases, recent strokes or cancer within the last 5 years.

Inclusion Criteria

I have narcolepsy, finished a TAK-861 study, and my doctor agrees I can join.

Exclusion Criteria

Participant has alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >1.5 times the upper limit of normal (ULN) at multiple visits in the parent study and the findings are of clinical significance, per investigator or sponsor opinion, or ALT/AST >1.5 times ULN during the screening period for participants with a dosing gap.

Participant has a positive urine screen for drugs of abuse (findings confirmed) and/or positive alcohol test during any visit in their prior TAK-861 study, or during the screening period for participants with a dosing gap.

I have had a stroke or mini-stroke 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 for up to approximately 5 years to evaluate safety and tolerability

Up to 5 years

Multiple visits (in-person and home health)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• TAK-861

Trial Overview The study tests the safety and tolerability of a drug called TAK-861 on individuals with type 1 and type 2 narcolepsy who participated in previous related trials. It aims to understand how well these patients can handle continued treatment.

Participant Groups

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

Participants will receive TAK-861 dose 2 for up to approximately 5 years.

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

Participants will receive TAK-861 dose 1 for up to approximately 5 years.

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

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]

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]

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]

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]

References

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

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

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

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

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

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

4. 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]

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

New developments in the management of narcolepsy. [2020]