A Study of TAK-781 in Healthy Volunteers and in Participants With Non-Cirrhotic Primary Sclerosing Cholangitis (PSC)

NCT07229911 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: TAK-781-1001
• Study Type: interventional
• Target: 134
• Locations: 1 country
• Sites: 1

Brief Summary

The main aim of this study is to see if the drug TAK-781 is safe for healthy volunteers and for participants with PSC. The study will also look at how well participants can tolerate TAK-781. In addition, the study will check how the body absorbs, uses, and gets rid of TAK-781 (Pharmacokinetics \[PK\]), how the drug affects the body (Pharmacodynamics \[PD\]), and how the body's immune system reacts to TAK-781 (Immunogenicity). The study consists of two phases (Phase 1a and 1b). Phase 1a includes two parts: Part 1 (Single Ascending Dose \[SAD\]) and Part 2 (Multiple Ascending Dose \[MAD\]). In Part 1, healthy participants will receive either single dose of TAK-781 or a placebo. A placebo looks the same as TAK-781 but has no medicine in it. In Part 2, healthy participants will receive multiple doses of TAK-781 or a placebo. In Phase 1b (Part 3), participants with large duct, non-cirrhotic PSC will receive a single dose of TAK-781. Participants will be in the study for about 36 weeks.

Conditions

Healthy Volunteers; Primary Sclerosing Cholangitis

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (4)

• Phase 1a (SAD and MAD) and Phase 1b: Number of Participants With Treatment-emergent Adverse Events (TEAEs)

  An AE is any untoward medical occurrence in a clinical trial participant, temporally associated with the use of the trial intervention, whether or not the occurrence is considered related to the trial intervention. TEAE is defined as any event emerging or manifesting at or after the initiation of treatment with a trial intervention or medicinal product or any existing event that worsens in either intensity or frequency following exposure to the trial intervention.

  Phase 1a (SAD) and 1b: From start of study drug administration up to End of Treatment (EOT)/Early termination (ET) (up to Week 20); Phase 1a (MAD): From start of study drug administration up to EOT/ET (up to Week 32)

• Phase 1a (SAD and MAD) and Phase 1b: Number of Participants With Clinically Significant Changes in Clinical Laboratory Values

  Laboratory parameters will include hematology, chemistry and urinalysis. Any clinically significant change in laboratory values will be determined at the investigator's discretion.

  Phase 1a (SAD) and 1b: From start of study drug administration up to EOT/ET (up to Week 20); Phase 1a (MAD): From start of study drug administration up to EOT/ET (up to Week 32)

• Phase 1a (SAD and MAD) and Phase 1b: Number of Participants With Clinically Significant Changes in 12-Lead Electrocardiogram (ECG) Parameters

  The 12-lead ECG will be evaluated. Any clinically significant change in ECG assessment will be determined at the investigator's discretion.

  Phase 1a (SAD) and 1b: From start of study drug administration up to EOT/ET (up to Week 20); Phase 1a (MAD): From start of study drug administration up to EOT/ET (up to Week 32)

• Phase 1a (SAD and MAD) and Phase 1b: Number of Participants With Clinically Significant Changes in Vital Sign Values

  Vital signs will include measurement of oral body temperature, supine blood pressure and heart rate. Any clinically significant change in vital signs will be determined at the investigator's discretion.

  Phase 1a (SAD) and 1b: From start of study drug administration up to EOT/ET (up to Week 20); Phase 1a (MAD): From start of study drug administration up to EOT/ET (up to Week 32)

Secondary Outcomes (8)

• Phase 1a and 1b: Maximum Observed Plasma Concentration (Cmax) of TAK-781

  Predose up to 2 days post-dose

• Phase 1a and 1b: Time of First Occurrence of Plasma Cmax (Tmax) of TAK-781

  Predose up to 2 days post-dose

• Phase 1a and 1b: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUCinf) of TAK-781

  Predose up to 2 days post-dose

• Phase 1a and 1b: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration (AUClast) of TAK-781

  Predose up to 2 days post-dose

• Phase 1a: Percentage Change From Baseline in TE Biomarker Area Under the Effect Curve 0 to 9 Hours (AUEC0-9h)

  Phase 1a: 0 to 9 hours post-dose

Study Arms (5)

Phase 1a (Part 1): TAK-781 SAD

EXPERIMENTAL

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).

Drug: TAK-781

Phase 1a (Part 1): Placebo SAD

PLACEBO COMPARATOR

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

Drug: Placebo

Phase 1a (Part 2): TAK-781 MAD

EXPERIMENTAL

Healthy participants will receive multiple doses 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.

Drug: TAK-781

Phase 1a (Part 2): Placebo MAD

PLACEBO COMPARATOR

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

Drug: Placebo

Phase 1b (Part 3): TAK-781

EXPERIMENTAL

Participants with non-cirrhotic PSC will receive a single dose of TAK-781 injection on Day 1 during the pre-defined treatment period. Part 3 will not begin until the SAD portion of the trial is considered complete.

Drug: TAK-781

Interventions

TAK-781 DRUG

TAK-781 injection.

Phase 1a (Part 1): TAK-781 SAD; Phase 1a (Part 2): TAK-781 MAD; Phase 1b (Part 3): TAK-781

Placebo DRUG

TAK-781 matching placebo injection.

Phase 1a (Part 1): Placebo SAD; Phase 1a (Part 2): Placebo MAD

Eligibility Criteria

• Age: 18 Years - 68 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The participant is willing and able to fully comply with all trial procedures and requirements, in the investigator's opinion.
• The participant has provided informed consent (that is, in writing, documented via a signed and dated informed consent form (ICF) or electronic consent \[e-consent\] if applicable) and any required privacy authorization prior to the initiation of any trial procedures.
• Male at birth and female at birth participants aged 18 to 68 years, inclusive, at the time of consent.
• The participant is judged to be in good health (for example, no evidence of cardiovascular, liver, metabolic, gastroenterological, or kidney disease) by the investigator, based on clinical evaluations including laboratory safety tests, medical history, physical examination, ECG, and vital sign measurements performed at the first screening visit.
• The participant must have a body mass index (BMI) of less than 30.0 kilograms per square meter (kg/m\^2) at the time of screening.
• Has not had frequent or heavy use (that is, near-daily) of medical or recreational cannabis for at least 3 months before screening.
• The participant must not be a person of childbearing potential (POCBP) defined by at least 1 of the following criteria:
• Surgically sterile for at least 6 weeks at screening (defined as having undergone one of the following procedures: hysterectomy, bilateral oophorectomy, or bilateral salpingectomy).
• Postmenopausal at screening (defined as no menses for 12 months without an alternative medical cause). A high follicle-stimulating hormone (FSH) level (greater than or equal to \[\>=\]40 international units/liter \[IU/L\] in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
• Has no uterus as a result of congenital condition. The participant must not donate ova for at least 6 months after the last dose of trial intervention.
• Male participants (based on sex at birth) must use highly effective contraception, from the date of signing the ICF, throughout the duration of the trial, and for 6 months after the last dose of trial intervention. The participant must not donate sperm for at least 6 months after the last dose of trial intervention.
• The participant is willing and able to fully comply with all trial procedures and requirements, in the investigator's opinion.
• The participant has provided informed consent (that is, in writing, documented via a signed and dated ICF or e-consent if applicable) and any required privacy authorization prior to the initiation of any trial procedures.
• Male at birth and female at birth participants aged 18 to 68 years, inclusive, at the time of consent.
• Confirmed diagnosis of large-duct PSC based on any 2 of the following 3 criteria:

You may not qualify if:

• The participant is an employee of the sponsor or trial site, or an immediate family member (for example, spouse, parent, child, sibling) 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 (for example, food, drug, latex allergy) or has had an anaphylactic reaction or significant intolerance to prescription or nonprescription drugs or food.
• The participant has a history or clinical evidence of bleeding diathesis or any coagulation disorder.
• The participant has a medical history of prior cholecystectomy.
• The participant has participated in another investigational trial with other investigational agents or devices for any indication within 4 weeks or within 5 half-lives, for investigational drugs or biologics with a known half-life (whichever is longer), before the screening visit. The interval window from the previous trial will be derived from the date of the last trial medical procedure, and/or AE related to the trial IP or procedure in the previous trial to the screening visit of the current trial. Exceptions may be made for observational, natural history and nonintervention type studies with sponsor or designee approval.
• The participant has an ALT and/or AST value greater than the ULN during screening.
• The participant has abnormal cholesterol: total cholesterol \>240 milligrams per deciliter (mg/dL), low-density lipoprotein cholesterol (LDL-C) (\>160 mg/dL), high-density lipoprotein cholesterol (HDL-C) (less than \[\<\]35 mg/dL), and triglycerides (\>250 mg/dL) at screening. Lipid parameters may be repeated once under fasting conditions at the principal investigator's discretion. Eligibility will be determined based on the repeated results.
• The participant has eGFR rate \<=90milliliter per minutes per 1.73 square meters (mL/min/1.73m\^2) at screening.
• The participant screening ECG (triplicate) reveals a QT interval with Fridericia correction method (QTcF) \>450 millisecond (ms) (male) or \>460 ms (female).
• The participant has a confirmed supine systolic blood pressure \>=140 millimetres of mercury (mmHg) and/or diastolic blood pressure \>=90 mmHg at screening. If the participant's supine blood pressure exceeds these thresholds, the measurement should be repeated twice after the participant has remained in the supine position for at least 10 minutes. The average of the three supine blood pressure measurements will be used to determine eligibility.
• Resting BP is defined as a BP measurement obtained after the participant has been resting for a minimum of 5 minutes.
• The participant has a resting heart rate (HR) outside of the range of 55 to 100 beats per minute (bpm) (inclusive) at screening, confirmed on repeat testing within a maximum of 30 minutes. Athletic participants with HR \<55 bpm may be enrolled based on the investigator's judgement provided that the HR is \>45 bpm.
• The participant has a positive urine screen for drugs of abuse at screening and Day -3.
• History of any malignancy diagnosed or treated within 5 years prior to screening.

Sponsors & Collaborators

• Takeda: lead

Study Sites (1)

ICON

Salt Lake City, Utah, 84124, United States

RECRUITING

Related Links

• Click here for more information about this trial in easy-to-understand language, including a Plain Language Summary of the results if the trial has been completed.
• Click here to ask Takeda's chatbot for comprehensive and easy-to-understand information about clinical trials - even across products and indications - in your local language.

MeSH Terms

Conditions

Cholangitis, Sclerosing

Condition Hierarchy (Ancestors)

Cholangitis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Central Study Contacts

Takeda Contact

CONTACT

+1-877-825-3327; medinfoUS@takeda.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Phase 1a will be double blind, whereas Phase 1b will be non-blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2025
• First Posted: November 17, 2025
• Study Start: January 7, 2026
• Primary Completion (Estimated): April 6, 2028
• Study Completion (Estimated): April 6, 2028
• Last Updated: March 5, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

US (1)