Recruiting PHASE1 Healthy Volunteers

New treatment option for Healthy Volunteers

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

ClinicalTrials.gov ID: NCT07229911

What this study is testing

What is TAK-781?

TAK-781 is an investigational medicine, given as an injectable medicine, being studied as a potential treatment for healthy volunteers.

Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.

What it's testing: 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.

Phase 1: an early, usually small safety study
Time commitment: about 36 weeks
You might receive a placebo (an inactive treatment) instead of the study drug.

A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.

Who can take part

Ages 18 to 68. Healthy volunteers may be eligible.

You may be able to join if

Phase 1a (SAD and MAD)
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...
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)...

You likely can't join if

Phase 1a (SAD and MAD)
The participant is an employee of the sponsor or trial site, or an immediate family member (for example, spouse, parent, child, sibling) of an...
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...
The participant has a history or clinical evidence of bleeding diathesis or any coagulation disorder.
The participant has a medical history of prior cholecystectomy.

See the full eligibility criteria

Who can join

Phase 1a (SAD and MAD)
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...
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...
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]...
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...
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...
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:
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.
The participants must have a fibrogenesis biomarker over pre-defined level.
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.
No evidence of cholangiocarcinoma or any other malignancy on magnetic resonance imaging (MRI) at screening.
Participants with a certain concomitant disease are allowed to enroll if pre-defined criteria are met.
Participants must have certain additional laboratory parameters in specified ranges at screening.
Has not had frequent or heavy use (that is, near-daily) of medical or recreational cannabis for at least 3 months before screening.
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...
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.
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.

What rules you out

Phase 1a (SAD and MAD)
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...
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...
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...
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 [\...
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 history of torsades de pointes, clinically significant ventricular arrhythmias (for example, ventricular tachycardia), heart block (excluding first-degree atrioventricular block), congenital long...
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...
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...
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.
The participant consumes excessive amounts (defined as greater than 600 milligram (mg) of caffeine) of coffee, tea, cola, energy drinks, or other caffeinated beverages per day.
Has a positive pregnancy test result during the screening period.
Participants who test negative for hepatitis B surface antigen (HBsAg) but positive for hepatitis B core antibody (HBcAb) would be considered eligible if hepatitis B virus (HBV) deoxyribonucleic acid (DNA) results are...
Participants who test positive for hepatitis C virus (HCV) ribonucleic acid (RNA) at screening. Participants who are hepatitis C antibody (HCVAb) positive without evidence of HCV RNA may be considered eligible...
The participant tests positive for human immunodeficiency virus (HIV) at screening or currently receiving antiretroviral therapy.
Has undergone major surgery or donated or lost 1 unit of blood (approximately 500 milliliters [mL]) within 4 weeks before the screening visit.
Currently has or previously had a significant illness, as judged by the investigator, within 2 weeks of the first dose of trial intervention.
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...
The participant is unable to refrain from or anticipate using smoking, vaping or nicotine-containing products 2 weeks before screening until the last follow-up visit.
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...
Presence of documented secondary sclerosing cholangitis (such as ischemic cholangitis, recurrent pancreatitis, intraductal stone disease, severe bacterial cholangitis, surgical or blunt abdominal trauma, recurrent...
Immunoglobulin G4-related Sclerosing Cholangitis based on historical diagnosis.
Evidence of compensated cirrhosis. All participants will undergo a standardized cirrhosis exclusion assessment during screening including clinical, laboratory, and imaging evaluation (non-contrast MRI/ magnetic...
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).
The participant has a medical history of prior cholecystectomy.
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...
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...
Model for End-Stage Liver Disease score \>11.
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.
Concomitant overlap syndrome with primary biliary cholangitis (PBC) as diagnosed by either historical:
Positive anti-mitochondrial autoantibodies, or
Biopsy suggestive for PBC.
Clinically significant acute or chronic liver disease of an etiology other than PSC.
Presence of a dominant stricture of clinical concern on MRCP at screening. However: \- Participants with dominant stricture could be enrolled if the investigator determines that there is no evidence on MRI or...
Placement of a bile duct stent or percutaneous bile duct drain within 3 months of screening. However: \- Participants who had undergone a stricture balloon dilation procedure can enroll in the trial after at least 4...
History, evidence, or high suspicion of cholangiocarcinoma or other hepatobiliary malignancy based on imaging, laboratory values, and/or clinical symptoms.
Ascending cholangitis within 60 days prior to screening and through Day 1. 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.
Prior liver transplantation.
Screening ECG with clinically significant abnormalities as determined by the investigator.
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 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...
The participant tests positive for HIV at screening or currently receiving antiretroviral therapy.
History of malignancy diagnosed or treated within 5 years prior to screening.
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...
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.
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...
Use of any prohibited concomitant medication is not allowed unless the participant has completed the washout period prior to Day 1.
Participants should not be currently taking ursodeoxycholic acid, unless they have completed the washout period prior to Day 1.
Severe allergic or anaphylactic reactions to any components of N-acetylgalactosamine small-interfering RNA therapeutics.
Use of any investigational drug, biologic, or medical device, or participation in an treatment clinical trial, is prohibited within 4 weeks prior to screening or within 5 elimination half-lives for investigational drugs...
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.
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.
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.
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...

The study team makes the final eligibility decision.

Where it's taking place

Salt Lake City, Utah, United States

Compensation & support

A stipend or compensation may be offered.

Compensation mentioned.

ClinicalTrials.gov doesn't provide a reliable structured field for payment or travel support - confirm details with the study team.

Questions & answers

Do participants get paid in this trial?

This study's listing includes signals that participants may be compensated or receive a stipend. Amounts vary and are set by the study team - confirm the details with them.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The study runs about 36 weeks per participant, based on its public description. The team confirms the exact schedule and number of visits before you enroll.

Who can join this trial?

This study is enrolling all sexes, 18 years to 68 years. Healthy volunteers may be eligible. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include Salt Lake City, Utah, United States. Enter your location above to see the nearest site and check your eligibility.

Explore other conditions

Obesity Type 2 diabetes Type 1 diabetes Prediabetes Weight loss Metabolic syndrome High cholesterol High triglycerides High blood pressure PCOS Hypothyroidism Thyroid disease Gout Fatty liver disease (NAFLD/NASH)Heart failure Coronary artery disease

BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.