A Study of TAK-781 in Healthy Volunteers and in Participants With Non-Cirrhotic Primary Sclerosing Cholangitis (PSC)
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-68
SponsorTakeda
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Parallel
Treatments tested in this trial
TAK-781
DrugTAK-781 injection.
Placebo
DrugTAK-781 matching placebo injection.
Treatment groups
134 Participants
are divided into 5 treatment groupsGroup A: Phase 1a (Part 1): TAK-781 SADExperimental treatment 1 intervention
Group B: Phase 1a (Part 1): Placebo SADPlacebo comparator 1 intervention
Group C: Phase 1a (Part 2): TAK-781 MADExperimental treatment 1 intervention
Group D: Phase 1a (Part 2): Placebo MADPlacebo comparator 1 intervention
Group E: Phase 1b (Part 3): TAK-781Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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.
Time frame
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)2
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.
Time frame
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)3
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.
Time frame
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)4
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.
Time frame
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
1
Phase 1a and 1b: Maximum Observed Plasma Concentration (Cmax) of TAK-781
Cmax of TAK-781 will be reported.
Time frame
Predose up to 2 days post-dose2
Phase 1a and 1b: Time of First Occurrence of Plasma Cmax (Tmax) of TAK-781
Tmax of TAK-781 will be reported.
Time frame
Predose up to 2 days post-dose3
Phase 1a and 1b: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUCinf) of TAK-781
AUCinf of TAK-781 will be reported.
Time frame
Predose up to 2 days post-dose4
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
AUClast of TAK-781 will be reported.
Time frame
Predose up to 2 days post-dose Source ClinicalTrials.gov