The goal of this clinical trial is to learn if a single dose of the study drug, JST-010, is safe and tolerable when administered by injection into the arm or thigh muscle of healthy men and women aged 18 to 55. The main questions it aims to answer are: * Is a single injection of JST-010 safe? * What is the concentration of the JST-01 in the blood over time? * Do antibodies to JST-010 develop following a dose of JST-010? Researchers will compare JST-010 to Placebo to see if there are any differences in the safety and tolerability of a single dose at different dose levels. Participants will be confined to the clinic for the first 3 days. They will receive an injection on the second day, and then return for 9 more visits over the period of 1 year for: * Physical exam with vital signs * Electro-cardiogram (ECG) * Bood collection for clinical labs and research samples * Urine sample * Assessment of potential adverse effects and medications taken
This is a two-part, Phase 1, first-in-human (FIH), randomized, double-blind, placebo-controlled, single ascending dose (SAD) (Part 1) and dose expansion (Part 2) study to assess the safety, tolerability, and PK of a single dose of JST-010 administered IM to healthy participants. Part 1 will comprise a minimum of 3 SAD cohorts (Cohorts A, B, and C, with 14 participants per cohort), each evaluating a single dose of JST-010 administered IM. In each SAD cohort, 2 sentinel participants will be randomized 1:1 such that one participant receives JST-010 and 1 participant receives placebo. Following a favorable blinded safety review committee (SRC) review of sentinel safety data collected through Day 8, the remainder of the cohort (12 non-sentinel participants) will be randomized 5:1 to JST-010 or placebo, and the first block of 6 participants (5:1 JST-010 to placebo) will be dosed. The SRC will review the safety data collected during the first 48 hours after dosing for the first block of 6 participants dosed to determine whether the second block of 6 participants can be dosed. All safety data for all participants in the current cohort through Day 8 with cumulative prior safety data will be reviewed by the SRC in a blinded fashion for each dose cohort before escalating to the next dose cohort (for escalation from Cohort A to Cohort B and escalation from Cohort B to Cohort C); the SRC will have the ability to consult with the independent data monitoring committee (IDMC) as needed regarding these decisions. A recommendation on whether to implement Cohort D (along with a recommended dose of JST-010 to be evaluated in Cohort D) may be provided by the SRC following review of blinded safety data from Cohorts A, B, and C, or may be provided by the IDMC following review of unblinded safety, PK, and antidrug antibody (ADA) data from Cohorts A, B, and C.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
104
Active study drug
Placebo
PPD Las Vegas Clinical Research Unit
Las Vegas, Nevada, United States
RECRUITINGSafety and tolerability of a single dose of JST-010 when administered intramuscularly (IM) in healthy adults
1. Incidence of solicited local (injection site) and systemic AEs post-injection through Day 7 (with the inpatient and outpatient participant diaries being collected on Day 3 and Day 8, respectively). 2. Incidence of unsolicited AEs through end of study (EOS). 3. Incidence of SAEs, medically attended AEs (MAAEs), and AEs of special interest (AESIs) post-injection through EOS.
Time frame: 1) Local and systemic solicited AES from injection to Day 7, 2) All AEs post-injection to final visit at Week 48, 3) SAEs, MAAEs, and AESIs post-injection to final visit at Week 48
Pharmacokinetic Cmax of JST-010
Maximum observed concentration (Cmax)
Time frame: From enrollment to the end of study at 48 weeks
Pharmacokinetic Tmax of JST-010
Time to reach maximum observed concentration (Tmax)
Time frame: From enrollment to the end of study at 48 weeks
Pharmacokinetic Tlast of JST-010
The timepoint with the last quantifiable concentration (Tlast)
Time frame: From enrollment to the end of study at 48 weeks
Pharmacokinetic AUC0-D85 of JST-010
Area under the concentration versus time curve (AUC) from time 0 to Day 85 (AUC0-D85)
Time frame: From enrollment to the end of study at 48 weeks
Pharmacokinetic AUC0-t of JST-010
Area under the concentration versus time curve (AUC) from time 0 to the timepoint with the last quantifiable concentration (AUC0-t)
Time frame: From enrollment to the end of study at 48 weeks
Pharmacokinetic AUC0-inf of JST-010
AUC from time 0 extrapolated to infinity (AUC0-inf)
Time frame: From enrollment to the end of study at 48 weeks
Pharmacokinetic t1/2 of JST-010
Terminal elimination half-life (t1/2)
Time frame: From enrollment to the end of study at 48 weeks
Pharmacokinetic CL/F of JST-010
Apparent clearance after IM administration (CL/F)
Time frame: From enrollment to the end of study at 48 weeks
Pharmacokinetic Vz/F of JST-010
Apparent volume of distribution after IM administration (Vz/F)
Time frame: From enrollment to the end of study at 48 weeks
Evaluation of anti-JST-010 drug antibodies following IM administration of a single dose of JST-010
Immunogenicity: ADAs that develop to JST-010 or are pre-existing prior to administration of JST-010 may be associated with potential allergic reactions and could negatively impact the effectiveness of JST-010. ADAs will be evaluated throughout the duration of the trial. Participants who develop any AE associated with the development of ADAs will be followed until such AEs are resolved, stable, or judged by the investigator to be not clinically significant.
Time frame: From enrollment to the end of study at 48 weeks.
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