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

PHASE1ACTIVE_NOT_RECRUITING

The present First-In-Human (FIH) study (JUV-161-101) aims to assess the safety, tolerability, and pharmacokinetics (PK) of single 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 of a multiple-ascending dose (MAD) study 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.

Study details:

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.

Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

  1. Are males or nonpregnant females, ages 18 to 60 (inclusive) at time of signing Informed Consent with body mass index (BMI) 18 to 35 kg/m2
  2. Are willing and able to give informed consent and follow all study procedures and requirements
  3. Are able to understand the requirements of the study protocol
  4. Agree to complete all required study visits
  5. Are healthy, based on physical examination, medical history laboratory tests, vital signs and resting electrocardiograms
  6. Are willing to abstain from caffeine and nicotine while in the Study Unit
  7. Have negative screens for alcohol and drugs of abuse at screening and admission
  8. Are willing to abstain from all alcoholic beverages and cannabinoids for 48 h prior to dosing through Post-dosing visit on Study Day 6.
  9. Females must be either of non-childbearing potential or of child-bearing potential and using at least one of the following acceptable methods of contraception from at least 30 days prior to the time of informed consent through the time of study drug administration and for 8 weeks after last administration of study drug.
  10. Men who are sexually active and males with partners of child-bearing potential must use forms of medically acceptable birth control during the study drug treatment period and for 16 weeks after the last administration of study drug.
  11. Have NOT participated in a clinical study utilizing an investigational agent within 28 days or within 5 half-lives of the investigational drug (whichever is longer) prior to Screening

Exclusion criteria

  1. Are unwilling or unable to comply with study procedures, including follow-up, as specified by the protocol, or unwilling to cooperate fully with the Investigator
  2. Have a history of drug or alcohol abuse within 3 months of Screening
  3. Have an active malignancy or have a history of malignancy within the 5 years prior to Screening. (Subjects with prior basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that were successfully treated may be enrolled.)
  4. Have any of the following known active infections: Infection requiring systemic antiviral or antimicrobial therapy that would not have been completed within 30 days prior to screening, Known history or positive test result for HIV, HBV or HCV
  5. Have any clinical history or other active medical condition, psychiatric disorder or clinically significant laboratory abnormality, vital sign, ECG abnormality or other finding that, in the investigator's opinion, is likely to increase the risk of study participation, confound study results, or interfere with study conduct or adherence
  6. Have any of the following: History of diabetes, History of bleeding disorder or excessive bleeding, Impaired renal function (estimated glomerular filtration rate [eGFR] <60ml/min/1.73m2, using the CKD-EPI (2021 equation)), Platelet count < 125 X 109/L, INR > ULN, Electrocardiogram (ECG) showing QTcF > 470 msec female or > 450 msec male
  7. Have received Treatment with any prescription medication within 14 days prior to screening (exception: contraceptives are permitted), Treatment with any non-prescription medication within 7 days or 5 half-lives (whichever is longer) prior to dosing (exception: acetaminophen up to 2 g per day prior to dosing is permitted), Any vaccination (therapeutic or prophylactic) within 30 days prior to screening and agree to not receive any vaccination during the course of the study
  8. Prior exposure to JUV-161 or have known allergies to any components of the JUV-161 formulation
  9. History of immune reaction to any biologic therapy
  10. Donation or loss of greater than 1 unit (450 mL) of blood or donation of plasma through plasmapheresis within 7 days prior to screening.

Eligibility

Age eligible for study : NA

Healthy volunteers accepted : No

Gender eligible for study: ALL

Things to know

Study dates

Study start:

Primary completion:

Study completion finish:

study type

Study type

TREATMENT

phase

Phase

    PHASE1

trial

Study ID

NCT06918925

Intervention or treatment

DRUG: JUV-161, Placebo

Conditions

  • Healthy Volunteer

  • Condition: Healthy Volunteer

  • DRUG: JUV-161, Placebo

  • Melbourne, Victoria, Australia

  • Sponsor: Juvena Therapeutics

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Research sites nearby

Closest Location:

Nucleus Network Pty Ltd

Select from list below to view details:

  • Nucleus Network Pty Ltd

    Melbourne, Victoria, Australia

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Who is running the clinical trial?

JT

Juvena Therapeutics

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/ArmIntervention/Treatment
ACTIVE_COMPARATOR: JUV-161
  • Single-ascending dose administration of JUV-161/ 5 cohorts of 6 subjects SAD 1 JUV-161 0.10 mg/kg 6 subjects SAD 2 JUV-161 0.30 mg/kg 6 subjects SAD 3 JUV-161 1.00 mg/kg 6 subjects SAD 4 JUV-161 3.00 mg/kg 6 subjects SAD 5 JUV-161 5.0 mg/kg 6 subjects SAD 6 JUV-161 10.0mg/kg 6 subjects
  • MAD 1 JUV-161 0.10 mg/kg 6 subjects X 3 doses MAD2 JUV-161 3.00 mg/kg 6 subjects X 3 doses MAD3 JUV-161 5.0 mg/kg 6 subjects x 3 doses
Drug: JUV-161, Placebo
    PLACEBO_COMPARATOR: Placebo-Controlled
    • SAD1 placebo 2 subjects X 1 dose SAD 2 placebo 2 subjects X 1 dose SAD 3 placebo 2 subjects X 1 dose SAD 4 placebo 2 subjects X 1 dose SAD 5 placebo 2 subjects X 1 dose SAD 6 placebo 2 subjects X 1 dose
    • MAD 1 placebo 2 subjects x 3 doses MAD 2 placebo 2 subjects x 3 doses MAD 3 placebo 2 subjects x 3 doses
    Drug: JUV-161, Placebo

      What is the study measuring?

      Primary Outcome

      MeasureDescriptionTime Frame
      Incidence of treatment-emergent adverse eventsNot SpecifiedFrom enrollment through to safety follow-up Visit on Day 60
      Number of participants with treatment-emergent potentially clinically-significant safety abnormalities in safety laboratory parametersNot SpecifiedFrom enrollment through to safety follow-up Visit on Day 60
      Number of participants who have changes from baseline in electrocardiogram values in QTcF intervalsNot SpecifiedFrom enrollment through the safety follow-up visit on Day 60
      Number of participants who have changes from baseline in heart rate ( beats per minute)Not SpecifiedFrom enrollment through the safety follow-up visit on Day 60
      Number of participants who have a change from baseline in systolic and diastolic blood pressure (mmHg)Not SpecifiedFrom enrollment through the safety follow-up visit on Day 60

      Secondary Outcome

      MeasureDescriptionTime Frame
      Maximum observed plasma concentration (Cmax)Not SpecifiedDay 1 pre-dose and at 1, 2, 6, 12, 24, 36, 48, 60 and 72 hours Day 6,8,11,15,18,21 and 60
      Time to the maximum measured plasma concentration (Tmax):Not SpecifiedUp to 60 days
      Area under the concentration-time curve from time zero through to infinity (AUC0-∞)Not SpecifiedUp to 60 days.
      Terminal elimination half-life in plasma (t1/2)Not SpecifiedUp to 60 days
      Are you running this trial?If you're a clinic or sponsor, you can claim this study.
      Claim this trial

      References

      Clinical Trials Gov: First-In-Human Study to Evaluate Single Ascending Doses of JUV-161 in Healthy Adult Volunteers

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