Phase 1a/1b Study of TRB-061 in Healthy Participants & Patients With Atopic Dermatitis

Official title

A Phase 1a/1b Randomized, Double-Blind, Placebo-Controlled, 3-Part Study to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Subcutaneous Doses of TRB-061 in Healthy Participants and in Patients With Moderate-to-Severe Atopic Dermatitis

Overview

This Phase 1a/1b randomized, double-blind, placebo-controlled study evaluates the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of subcutaneously (SC) administered TRB-061 in healthy adults and patients with moderate-to-severe atopic dermatitis (AD). The number of dosing cohorts may be increased or decreased in Part 1 (SAD) or Part 2 (MAD). Part 1 (SAD): Healthy participants receiving single doses of TRB-061 or placebo. Part 2 (MAD): Healthy participants receiving multiple doses (3 doses over 8 weeks) of TRB-061 or placebo. Part 3 (Phase 1b): Participants with moderate-to-severe AD receiving repeated doses (4 doses over 12 weeks) of TRB-061 or placebo.

Detailed description

Healthy adults will receive a single-ascending dose (SAD) of placebo or TRB-061 in cohorts of 8 (6 active, 2 placebo). Safety data will be reviewed before dosing the remaining participants. Follow-up lasts 12 weeks post-dosing. Treatment in the multiple-ascending dose (MAD) phase will be initiated after SAD cohort safety review is completed. Healthy adults will receive 3 doses of TRB-061 or placebo every 4 weeks (Q4W) over 8 weeks. Follow-up lasts 10 weeks post-last dose.

Participants with moderate-to-severe AD (Phase 1b) will be randomized to receive one of two dose levels of TRB-061 or placebo for 12 weeks (Q4W) in Period 1. In Period 2, participants will have the option to consent to a cross over treatment where those who previously received placebo will receive TRB-061 and those who received TRB-061 will receive placebo Q4W for 12 weeks followed by a Follow Up period through End of Study (EOS). Participants who do not consent to receive crossover treatment will continue study visits including efficacy and safety assessments through the EOS visit.

Interventions

• Drug TRB-061
  Single subcutaneous injection of TRB-061 at escalating doses
• Drug TRB-061
  Subcutaneous TRB-061 administered every 4 weeks for a total of 4 doses
• Drug TRB-061
  Subcutaneous TRB-061 administered every 4 weeks for 3 doses
• Drug Placebo
  Single and multiple subcutaneous doses of placebo matching TRB-061 in patients

Primary outcome measures

• Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time frame: From Screening to Day 85 (SAD), Up to Day 127 (MAD); up to Day 253 (Phase 1b)]

Secondary outcome measures (1)

• Pharmacokinetic (Maximum Observed Plasma Concentration, Cmax) [Time frame: Up to Day 85 (SAD), Up to Day 127 (MAD); up to Week 37 (Phase 1b)]

Eligibility criteria

Inclusion criteria

• Male or female participants aged 18 to 70 years, inclusive, at the time of informed consent.
• Body weight ≥50 kg and a body mass index (BMI)between 18.5 and 35.0 kg/m², inclusive.
• Participant is in good general health as determined by the investigator, based on medical history, physical examination, and clinical laboratory tests.
• For healthy participants (SAD and MAD): no clinically significant abnormalities in ECGs at screening.
• For participants in Phase 1b: Confirmed diagnosis of AD with onset of symptoms at least 1 year prior to Screening.
• Must be nonpregnant and nonlactating with negative pregnancy tests at screening and prior to dosing.
• Must be a non-smoker or ≤5 cigarettes per week for the past 6 months (SAD/MAD only).
• For participants in Phase 1b: Moderate-to-severe AD at Screening and at Day 1 visit
• Agrees to abstain from the use of tetrahydrocannabinol (THC)-containing products while on study.

Exclusion criteria

• History of any clinically significant disease or disorder which, in the opinion of the investigator, may put the participant at risk or interfere with study results.
• History or presence of any condition requiring systemic immunosuppressive or immunomodulatory therapy within a defined period before screening.
• Use of any biologic agent (e.g., monoclonal antibodies) within 3 months or 5 half-lives (whichever is longer) before Day 1.
• Participation in another investigational drug trial within 30 days or 5 half-lives of the prior investigational product (whichever is longer) before Day 1.
• History of hypersensitivity or allergic reaction to any component of the study drug or placebo formulation.
• Known active or latent tuberculosis (TB) infection. or history of incomplete TB treatment.
• Positive test at screening for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) RNA, or human immunodeficiency virus (HIV).
• Active infection or history of serious infections within 4 weeks prior to Day 1.
• Clinically significant ECG abnormalities (e.g., QTcF>470 ms) or other cardiac risk factors.
• Abnormal and clinically significant laboratory values at screening.
• Use of live vaccines within 4 weeks before Day 1.
• Use of systemic corticosteroids, immunosuppressants, or immunomodulatory drugs within protocol-defined washout periods (Part 3 only).
• Recent history of alcohol or drug abuse as defined per protocol.
• Use of tobacco/nicotine products beyond protocol-allowed limits (SAD and MAD).
• Positive cotinine test at check-in (SAD/MAD only).
• Any other reason, in the opinion of the investigator or sponsor, that would make the participant unsuitable for participation in the study.
• Any medical or psychiatric condition that, in the opinion of the Investigator or Sponsor's medical monitor, would place the participant at risk, interfere with study participation, or interfere with the interpretation of study results.
• Surgery within the past 90 days prior to dosing as determined by the Investigator or Sponsor's medical monitor to be clinically relevant or planned surgery to be performed during the study and 30 days after the last dose of study drug

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

New Zealand · 8 centers

• Momentum Clinical Research Pukekohe — Pukekohe
• Momentum Clinical Research Dunedin — Dunedin
• Pacific Clinical Research Network-Tasman — Nelson
• Clinical Trials New Zealand Ltd — Hamilton
• Medical Research Institute of New Zealand — Newtown
• Pacific Clinical Research Network-Wellington — Upper Hutt
• Momentum Clinical Research Kapiti — Waikanae
• Pacific Clinical Research Network-West Auckland — Auckland

Australia · 7 centers

• Paratus Clinical Research - Canberra Trial Clinic — Belconnen
• Paratus Clinical Brisbane Pty Ltd — Albion
• Paratus Clinical Research Western Sydney — Blacktown
• Paratus Clinical Research Central Coast — Kanwal
• Cornerstone Centre for Clinical Research — Coorparoo
• CMAX Clinical Research Pty Ltd — Adelaide
• Paratus Clinical Research Melbourne — Melbourne

Identifiers

NCT: NCT06934252 · TRB061-AD-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗