TAK-781 for Primary Sclerosing Cholangitis

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Takeda

Must not be taking: Antiretrovirals, Ursodeoxycholic acid

Disqualifiers: Cirrhosis, Cholecystectomy, HIV, others

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to test the safety and tolerability of a new drug, TAK-781, in both healthy individuals and those with primary sclerosing cholangitis (PSC), a liver disease that inflames and scars bile ducts. The trial will also examine how the body processes TAK-781 and the immune system's response to it. This study is open to healthy individuals and those diagnosed with PSC who do not have cirrhosis (severe liver scarring). Participants will be involved in the study for about 36 weeks. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial protocol does not clearly specify if you must stop taking your current medications. However, it mentions that participants should refrain from using prohibited or excluded medications and complete any required washout period before starting the trial. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that TAK-781 is likely to be safe for humans?

Research on TAK-781 remains in the early stages, focusing on its use for primary sclerosing cholangitis (PSC). As a Phase 1 study, this marks the first time the treatment is tested in humans. This phase determines if TAK-781 is safe and how well people tolerate it.

In these initial studies, both healthy volunteers and people with PSC receive TAK-781 to check for any side effects, which are closely monitored. At this stage, there may be limited information on how people react to TAK-781. However, reaching this phase indicates that early lab tests and animal studies suggested it could be safe enough for human trials.

Since TAK-781 is not yet approved for any condition, the main focus is on ensuring its safety before further testing. Participants in this trial help researchers gather important safety information. ^{1 2 3 4 5}

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

Most current treatments for Primary Sclerosing Cholangitis (PSC), like ursodeoxycholic acid, primarily aim to manage symptoms and slow disease progression, but they don't target the root cause. TAK-781 is unique because it offers a new approach by targeting specific pathways involved in the disease process, potentially offering more effective management. Researchers are excited about TAK-781 because it might not only address symptoms but also modify the underlying disease mechanism, offering hope for better outcomes in PSC patients.

What evidence suggests that TAK-781 might be an effective treatment for PSC?

Research is investigating TAK-781 as a potential treatment for primary sclerosing cholangitis (PSC), a liver disease affecting the bile ducts. Although limited information exists on TAK-781's effectiveness for PSC, the drug targets processes believed to be involved in the disease. In this trial, some participants will receive TAK-781, while others will receive a placebo. Early studies examine the body's handling of the drug, its safety, and its effects on both healthy individuals and those with PSC. These initial studies aim to lay the groundwork for future research on TAK-781's potential benefits for PSC patients. More information is needed to confirm its effectiveness specifically for PSC. ^{1 3 6 7 8}

Who Is on the Research Team?

Study Director

Principal Investigator

Takeda

Are You a Good Fit for This Trial?

This trial is for healthy individuals and those with a liver condition called non-cirrhotic Primary Sclerosing Cholangitis (PSC). Participants will be involved in the study for approximately 36 weeks. Specific eligibility criteria details are not provided, but typically include age, health status, and no conflicting medications or conditions.

Inclusion Criteria

I am considering joining an early phase clinical trial.

The participant must not be a person of childbearing potential.

I am a man and will use effective birth control during and for 6 months after the trial.

Exclusion Criteria

The participant is an employee of the sponsor or trial site, or an immediate family member of an employee of the sponsor or trial site who is directly involved in the conduct of the trial.

The participant has a known hypersensitivity to any component of the formulation of TAK-781 or related compounds.

The participant has a history of significant multiple and/or severe allergies or anaphylactic reactions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1a Part 1 (SAD)

Healthy participants receive a single dose of TAK-781 or placebo

Up to 20 weeks

Multiple visits for dose administration and monitoring

Phase 1a Part 2 (MAD)

Healthy participants receive multiple doses of TAK-781 or placebo

Up to 32 weeks

Multiple visits for dose administration and monitoring

Phase 1b (Part 3)

Participants with non-cirrhotic PSC receive a single dose of TAK-781

Up to 20 weeks

Multiple visits for dose administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• TAK-781

Trial Overview The study tests TAK-781's safety and how it's processed by the body in both healthy volunteers and PSC patients. It has two phases: Phase 1a gives single or multiple doses to healthy people; Phase 1b gives a single dose to PSC patients. A placebo group is included for comparison.

How Is the Trial Designed?

Group I: Phase 1b (Part 3): TAK-781 Experimental Treatment 1 Intervention

Participants with non-cirrhotic PSC will receive a single dose of TAK-781 injection on Day 1 during the pre-defined treatment period.

Group II: Phase 1a (Part 2): TAK-781 MAD Experimental Treatment 1 Intervention

Healthy participants will receive multiple doses levels of TAK-781 injection across five cohorts (1 to 5), with or without a loading dose during the pre-defined treatment period. An additional cohort may be added to repeat a selected dose level and/or dosing regimen from one of the previously tested dose levels and/or dosing regimens in order to assess safety and tolerability, and/or to verify the level of TE.

Group III: Phase 1a (Part 1): TAK-781 SAD Experimental Treatment 1 Intervention

Healthy participants will receive a single dose of TAK-781 injection at different dose level cohorts (1-6) on Day 1 of the pre-defined treatment period. An additional cohort may be added to repeat a selected dose from one of the previously tested dose levels in order to assess safety and tolerability and/or to verify the level of target engagement (TE).

Group IV: Phase 1a (Part 1): Placebo SAD Placebo Group 1 Intervention

Healthy participants will receive TAK-781 matching placebo injection on Day 1 of the pre-defined treatment period.

Group V: Phase 1a (Part 2): Placebo MAD Placebo Group 1 Intervention

Healthy participants will receive multiple dose levels of TAK-781 matching placebo injection, with or without a loading dose during the pre-defined treatment period.

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

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07229911

NCT07229911 | A Study of TAK-781 in Healthy Volunteers ... The main aim of this study is to see if the drug TAK-781 is safe for healthy volunteers and for participants with PSC.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12245849/

Current status of pharmacotherapy for primary sclerosing ... The results found that fenofibrate treatment resulted in a significant decrease in AST and ALT in PSC patients (23). In a subsequent randomized, ...

3. scholars.duke.edu scholars.duke.edu/publication/1664157

Assessing patient-reported outcomes in primary sclerosing ... PURPOSE OF REVIEW: Patient-reported outcome (PRO) measures validated in primary sclerosing cholangitis (PSC) are needed for clinical trials.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11093571/

Patient-focused drug development in primary sclerosing ... Patient responses regarding clinical trial characteristics are displayed in Table 2. Overall, 67.3% of patients identified slowing progression ...

5. fda.gov fda.gov/media/185656/download?attachment

queryResult We are requesting our own records relating to Active Pharmaceutical Ingredient (“API”) samples taken during a May 14, 2024 to May 29, 2024 FDA inspection ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6824074/

A Prospective Trial of Withdrawal and Reinstitution of ... UDCA treatment has an uncertain impact on disease outcomes and has been reported in high doses to be associated with worse outcome in adults with PSC.

7. research.ed.ac.uk research.ed.ac.uk/files/211788111/Emerging_synthetic_drugs_for_the_treatment_of_liver_cirrhosis_main_manuscript_R1_clean.pdf

Emerging synthetic drugs for the treatment of liver cirrhosis primary sclerosing cholangitis (PSC) [61]. Although development of ... pharmacodynamic and safety data on CC-90001 are limited. In a phase 1b study in ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9235119/

Single Topic Conference on Autoimmune Liver Disease from ... The natural history of primary sclerosing cholangitis in 781 children: a multicenter, international collaboration. Hepatology. 2017;66(2):518–27. 10.1002 ...