A Study of TAK-781 for Primary Sclerosing Cholangitis (PSC) and in Healthy Volunteers
This study is testing an investigational drug called TAK-781. It aims to find out if TAK-781 is safe and tolerable for healthy volunteers and for people with Primary Sclerosing Cholangitis (PSC), a chronic liver disease. Researchers will also learn how your body processes TAK-781 and how your immune system reacts to it. The study is currently recruiting 134 participants, aged 18 to 68. Success in this early phase study means understanding the drug's safety and how well people tolerate it, which is measured by looking at side effects and changes in lab tests or heart readings.
- Study design
- This is an interventional study involving 134 participants. Some participants will receive TAK-781, while others will receive a placebo (an inactive substance that looks like the drug).
- What's involved
- Not specified in the trial record.
- Compensation
- Not stated in the trial record.
- Follow-up
- Participants will be followed for up to 20 or 32 weeks after starting the study drug, depending on the phase of the study.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT07229911
A Study of TAK-781 in Healthy Volunteers and in Participants With Non-Cirrhotic Primary Sclerosing Cholangitis (PSC)
Recruiting
PHASE1Ages 18–68InterventionalTreatmentTakeda
~134 participants
Updated 2026-03-05 on ClinicalTrials.gov
What's tested:TAK-781Placebo
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Phase 1a (SAD and MAD) and Phase 1b: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Measured over 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)
+3 more outcomes measured
Conditions
Where it's being run
1 sites across 1 statesUtah1
Study leadership
- Study Director · STUDY_DIRECTOR · Takeda
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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. 8. 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.
Historical evidence of an elevated alkaline phosphatase (ALP) greater than \[\>\] upper limit of normal (ULN) from any laboratory.
Historical liver biopsy with histologic features consistent with large-duct PSC, in the appropriate clinical context (such as cholestatic liver enzyme profile, inflammatory bowel disease \[IBD\] history).
Historical abnormal cholangiography consistent with PSC as measured by magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography, or percutaneous transhepatic cholangiography. 5. The participants must have a fibrogenesis biomarker over pre-defined level. 6. The participants must have evidence for moderate/advanced fibrosis but not cirrhosis as defined by enhanced liver fibrosis (ELF) \>=7.7 but less than or equal to(\<=)11.3 at Visit 1. 7. No evidence of cholangiocarcinoma or any other malignancy on magnetic resonance imaging (MRI) at screening. 8. Participants with a certain concomitant disease are allowed to enroll if pre-defined criteria are met. 9. Participants must have certain additional laboratory parameters in specified ranges at screening. 10. Has not had frequent or heavy use (that is, near-daily) of medical or recreational cannabis for at least 3 months before screening. 11. A female and male participant (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 ova or sperm for at least 6 months after the last dose of trial intervention. 12. A POCBP must have a negative serum pregnancy test at first screening visit and urine pregnancy test on second screening visit and Day 1 before dosing. 13. Participants must be able to be educated regarding the correct process/procedure, verbally state understanding and comply with the correct process/procedure of the administration SC IP for the duration of the trial.
Exclusion
A positive drug screen is exclusive unless it can be explained by a prescribed medication.
Participant with alcohol consumption greater than 4 units on any day or 14 units per week for male participants, or greater than 3 units on any day or 7 units per week for female participants \[1 unit of alcohol is present in one 12 ounce (oz)/355 mL beer (approximately 5 percent (%) alcohol), one 5 oz/148 mL glass of wine (approximately 12% alcohol), and one 1.5 oz/44 mL measure of 80-proof liquor (approximately 40% alcohol)\].
MRE liver stiffness \>= 4.32 kPa.
Liver surface nodularity or lobar redistribution.
Spleen volume \>400 mL/m\^2 body surface area or spleen length \>13 centimeter (cm).
Segmental parenchymal signal heterogeneity, periportal edema, or lobar atrophy.
Collateral vessels or signs of portal hypertension (for example, varices, recanalized umbilical vein).
Radiologist overall impression consistent with cirrhosis.
Serum albumin \<3.5 grams per deciliter (g/dL). 4. The participant has a medical history of prior cholecystectomy. 5. Participants will be excluded if they meet any of the following criteria: a diagnosis of decompensated liver disease, or evidence of new signs of decompensation or clinically meaningful deterioration in liver function during the screening period, based on the judgment of the investigator. This may include, but is not limited to, significant changes in the following parameters: total bilirubin, direct bilirubin, albumin, international normalized ratio (INR), creatinine, alanine transaminase (ALT), or aspartate transaminase (AST). 6. Presence or history of any of the following:
Ascites.
Hepatic encephalopathy.
Variceal bleeding.
Child-Pugh score \>6 (Class B or C), unless elevated INR is attributable to therapeutic anticoagulation. (Participants with compensated cirrhosis \[for example, Child-Pugh A\] will also be excluded if identified via the noninvasive cirrhosis exclusion algorithm, which includes assessment of ELF score, LSM, MRI/MRE, MRCP+, and clinical/laboratory parameters).
Model for End-Stage Liver Disease score \>11. 7. Concomitant overlap syndrome with autoimmune hepatitis as diagnosed at screening by AST or ALT \>5\*ULN, and historical:
Positive smooth muscle antibody and/or liver-kidney microsomal antibody (LKM), or
Immunoglobulin G (IgG) \>ULN, or
Biopsy suggestive for autoimmune hepatitis. 8. Concomitant overlap syndrome with primary biliary cholangitis (PBC) as diagnosed by either historical:
Positive anti-mitochondrial autoantibodies, or
Biopsy suggestive for PBC. 9. Clinically significant acute or chronic liver disease of an etiology other than PSC. 10. Presence of a dominant stricture of clinical concern on MRCP at screening. However:
Chronic preventive antibiotics for cholangitis are allowed in the trial.
Intermittent courses of antibiotics for the presumptive treatment of cholangitis are allowed if outside the 12-week window prior to screening. 14. Prior liver transplantation. 15. Screening ECG with clinically significant abnormalities as determined by the investigator. 16. Participants who test negative for HBsAg but positive for HBcAb would be considered eligible if HBV DNA results are negative at screening (as confirmed by HBV DNA PCR reflex testing performed by the central laboratory). Participants with positive HBV DNA test results will not be eligible. 17. Participants who test positive for HCV RNA at screening. Participants who are HCVAb positive without evidence of HCV RNA may be considered eligible (spontaneous viral clearance or previously treated and cured \[defined as no evidence of HCV RNA at least 12 weeks before baseline\]). 18. The participant tests positive for HIV at screening or currently receiving antiretroviral therapy. 19. History of malignancy diagnosed or treated within 5 years prior to screening. 20. The participant is unable to refrain from or anticipates using prohibited or excluded medications, herbal preparations, grapefruit juice, and other restricted substances or the required washout period prior to administration of the first dose of trial intervention throughout the trial and until the follow-up visit. 21. The participant has not had frequent or heavy use (\>=20 cigarettes per day) of smoking, vaping or nicotine-containing products or has not smoking-related complications. 22. Clinically relevant drug or alcohol abuse within 12 months of screening.
A positive drug screen is exclusive unless it can be explained by a prescribed medication.
Participant with alcohol consumption greater than 4 units on any day or 14 units per week for male participants, or greater than 3 units on any day or 7 units per week for female participants \[1 unit of alcohol is present in one 12 oz/355 mL beer (approximately 5% alcohol), one 5 oz/148 mL glass of wine (approximately 12% alcohol), and one 1.5 oz/44 mL measure of 80-proof liquor (approximately 40% alcohol)\]. 23. Use of any prohibited concomitant medication is not allowed unless the participant has completed the washout period prior to Day 1. 24. Participants should not be currently taking ursodeoxycholic acid, unless they have completed the washout period prior to Day 1. 25. Severe allergic or anaphylactic reactions to any components of N-acetylgalactosamine small-interfering RNA therapeutics. 26. Use of any investigational drug, biologic, or medical device, or participation in an interventional clinical trial, is prohibited within 4 weeks prior to screening or within 5 elimination half-lives for investigational drugs or biologics with a known half-life (whichever is longer). This restriction includes any pharmacologic, endoscopic, or other interventional procedures intended to modify or alter the course of PSC or its underlying disease processes. 27. History of clinically significant unstable or untreated illness or any other major medical disorder that may have interfered with participant treatment, assessment, or compliance with the protocol. 28. Any acute or chronic condition or other disease that, in the opinion of the investigator, would limit the ability of the participant to complete and/or participate in the clinical trial. 29. Presence of any other conditions (for example, geographic or social), actual or projected, that the investigator determines would restrict or limit the participation of the participant for the duration of the trial. 30. Individuals who are employed by the sponsor, a participating contract research organization (CRO), or the trial site - including permanent staff, temporary or contract workers, or designees directly involved in the conduct of the trial are excluded from participation. This exclusion also applies to immediate family members of employees of the sponsor, CRO, or trial site.
What this trial measures
- Phase 1a (SAD and MAD) and Phase 1b: Number of Participants With Treatment-emergent Adverse Events (TEAEs)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)
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 MAD) and Phase 1b: Number of Participants With Clinically Significant Changes in Clinical Laboratory ValuesPhase 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)
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 MAD) and Phase 1b: Number of Participants With Clinically Significant Changes in 12-Lead Electrocardiogram (ECG) ParametersPhase 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)
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 MAD) and Phase 1b: Number of Participants With Clinically Significant Changes in Vital Sign ValuesPhase 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)
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.