NCT06918925

First-In-Human Study to Evaluate Single and Multiple Ascending Doses of JUV-161 in Healthy Adult Volunteers

A Double-blind, Placebo-controlled, First-in-human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single- and Multiple-ascending Doses of JUV-161 Administered Subcutaneously to Healthy Adult Volunteers.

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: Juvena Therapeutics · Industry
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Accepted

Summary

The present First-In-Human (FIH) study (JUV-161-101) aims to assess the safety, tolerability, and pharmacokinetics (PK) of single and multiple subcutaneous (SC) doses of JUV-161 in healthy volunteers. The study design is well-established for FIH studies and appropriate to assess the preliminary safety and tolerability of new drug candidates. Data from this study will support conduct studies in patients with DM1 as well as supporting studies in other degenerative myopathies and other disorders for which preclinical efficacy data have been obtained.JUV-161 has not been previously been administered to human subjects.

Detailed description

This is a FIH, randomized, double-blind, placebo-controlled, single- and multiple-ascending dose study. The study will be conducted at a single center and will include healthy volunteer subjects. Enrollment in the SAD portion of the study will include up to 6 cohorts of 8 healthy adult volunteer subjects each of whom will receive a single dose of study drug (JUV-161, n=6; placebo, n=2). Enrollment in the MAD portion of the study will include up to 3 cohorts of 8 healthy adult volunteer subjects each of whom will receive multiple doses of study drug (JU161, n=6; placebo=2) For dosing, consideration of all relevant information obtained from in vitro and nonclinical toxicity studies was used to estimate no observed adverse effect levels (NOAELs) and a human equivalent dose (HED). Data from a 1-month non-human primate (cynomolgus monkeys) GLP study indicated that the NOAEL (HED) was ≥ 10 mg/kg. Using data from this study, modeling predicts that in humans the time to maximal concentration (Tmax) of JUV-161 will be 30-36 hours and the expected half-life (T1/2) of JUV-161 in humans will be approximately 80 hours. Based on this information, the planned starting dose of JUV-161 0.10 mg/kg was selected to mitigate known, unknown or theoretical risks associated with administration of JUV-161. Sentinel dosing will be implemented within each SAD cohort as an additional safety measure to enable detection of possible acute safety risk(s). In each SAD cohort, 2 subjects (1 JUV-161 and 1 placebo) will receive Study Drug on Study Day 1 (sentinel dosing). Following administration of study drug, a 72-hour period will be observed to detect the occurrence of reactions or significant adverse events (AEs). If safety and tolerability results are acceptable, 3 subjects will be dosed on Study Day 4. Following an additional 72-hour period and assuming no significant safety issues are identified, the final 3 subjects will be dosed on Study Day 7. A Safety Review Committee (SRC) will conduct two Safety Reviews per SAD dosing Cohorts only. On Study Day 3 of each SAD Cohort, the DMC SRC will review available clinical (including adverse events) and laboratory data from the Sentinel Dosing group to assess initial safety and tolerability of study drug. Assuming no safety issues are identified, dosing will proceed as described above. On Study Days 28 through 35 of each Cohort, after completion of dosing for each subject in the Cohort, the SRC will review available clinical (including adverse events) and laboratory data to assess initial safety and tolerability of study drug. The review will include clinical, laboratory and (as available) pharmacokinetic data through 20 days after administration of Study Drug to the final 3 subjects in the Cohort. This period includes, and extends beyond, the predicted 5 half-lives of serum concentration following administration of JUV-161 for all subjects. Assuming no safety issues are identified, dosing for the subsequent Cohort may be initiated. Additional study cohorts may be added, pending approval by the SRC, if the Sponsor believes additional dosing, safety, or pharmacokinetic data are required. Enrollment in the MAD portion of the study will include at least 3 cohorts of 8 healthy adult volunteer subjects. Each subject will receive study drug (JUV-161, n=6; placebo, n=2) weekly X3 (Study Days 1, 8, 15). Additional study cohorts may be added, pending approval by the SRC, if the Sponsor believes additional dosing, safety, or pharmacokinetic data are required. For the MAD cohorts, the dose range of 1.0 mg/kg to 5.0 mg/kg SC was chosen based on available safety data, a predicted efficacious dose for patients with DM1 (approximately 1 mg/kg SC once every week) and a practical SC dosing limitation. Following successful review of safety data following dosing in SAD Cohorts 1 through 3, assuming no safety issues have been identified, Study Drug dosing for Cohort MAD 1 may begin.In each cohort, 8 subjects will receive study drug (JUV-161, n=6; placebo, n=2). At the discretion of the investigator and considering study site requirements, administration of study drug in the respective cohorts may occur on the same day (full cohort enrollment) or subjects may be broken into sub cohorts with administration of study drug on separate days (split cohort enrollment).At least 18 days following conclusion of dosing of the last subject in the Cohort, safety data will be reviewed by the SRC. As noted above, 18 days exceeds the predicted 5 half-lives following SC administration of JUV-161. SRC review will include available data for all subjects dosed in the Cohort (including clinical, laboratory, vital sign, ECG, and PK data and adverse event reports); these data will be assessed for safety and tolerability. Prior to SRC data review for MAD cohorts, at least 6 subjects will have received all 3 doses of Study Drug as described in the protocol. Assuming no safety issues are identified, dosing for the subsequent Cohort may be initiated. The safety review will be documented.

Conditions

• Healthy Volunteer

Interventions

Type	Name	Description
DRUG	JUV-161, Placebo	Single-Ascending, Placebo-Controlled

Timeline

• Start date: 2025-04-14
• Primary completion: 2026-04-30
• Completion: 2026-06-30
• First posted: 2025-04-09
• Last updated: 2026-01-29

Locations

1 site across 1 country: Australia