Phase 1 Study on the Safety, Tolerability, and Pharmacokinetics of JST-018 in Healthy Adults

Official title

Phase 1, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of JST-018 in Healthy Adults

Overview

The goal of this clinical trial is to learn if a single dose of the study drug, JST-018, 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 administration of JST-018 safe? * What is the concentration of the JST-018 in the blood over time? * Do antibodies to JST-018 develop following a dose of JST-018? Researchers will compare JST-018 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

Detailed description

This is a Phase 1, first-in-human (FIH), randomized, double-blind, placebo-controlled, single ascending dose (SAD) study to assess the safety, tolerability, and PK of a single dose of JST-018 administered IM to healthy participants.

The study will be comprised of a minimum of 3 cohorts (Cohorts A, B, and C, with 12 participants per cohort), each evaluating a single dose of JST-018 administered IM. In each cohort, 2 sentinel participants will be randomized 1:1 such that one participant receives JST-018 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 (10 non-sentinel participants) will be randomized 4:1 to JST-018 or placebo, and will be dosed.

All safety data for all participants in the current cohort through Day 8 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); A recommendation on whether to implement Cohort D (along with a recommended dose of JST-018 to be evaluated in Cohort D) may be provided by the SRC following review of blinded safety data from Cohorts A, B, and C.

Interventions

• Biological JST-018 combination of 3 monoclonal antibodies
  Monoclonal antibodies
• Drug Placebo
  Placebo Comparator

Primary outcome measures

• Safety and tolerability of of JST-018 administered intramuscularly (IM) [Time frame: From injection to Day 7]
• Safety and tolerability of of JST-018 administered IM [Time frame: From injection to final visit at Week 48]
• Safety and tolerability of of JST-018 administered IM [Time frame: From injection to final visit at Week 48]
• Safety and tolerability of of JST-018 administered IM [Time frame: From injection to final visit at Week 48]
• Safety and tolerability of JST-018 administered as IM [Time frame: From injection to final visit at Week 48]
• Safety and tolerability of JST-018 administered as IM [Time frame: From injection to final visit at Week 48]

Secondary outcome measures (10)

• Pharmacokinetic Cmax of JST-018 [Time frame: From enrollment to the end of study at 48 weeks]
• Pharmacokinetic Tmax of JST-018 [Time frame: Time Frame: From enrollment to the end of study at 48 weeks]
• Pharmacokinetic Tlast of JST-018 [Time frame: From enrollment to the end of study at 48 weeks]
• Pharmacokinetic AUC0-t of JST-018 [Time frame: From enrollment to the end of study at 48 weeks]
• Pharmacokinetic AUC0-inf of JST-018 [Time frame: From enrollment to the end of study at 48 weeks]
• Pharmacokinetic t1/2 of JST-018 [Time frame: From enrollment to the end of study at 48 weeks]
• Pharmacokinetic CL/F of JST-018 [Time frame: From enrollment to the end of study at 48 weeks]
• Pharmacokinetic Vz/F of JST-018 [Time frame: From enrollment to the end of study at 48 weeks]
• Evaluation the effect of anti-drug antibodies (ADA) [Time frame: From enrollment to the end of study at 48 weeks]
• Evaluate if and to what extent ADAs develop following a single dose of JST-018 [Time frame: From enrollment to the end of study at 48 weeks]

Eligibility criteria

Inclusion criteria

• Healthy men or women 18 to 55 years of age
• BMI between 18 and 32 kg/m2
• Negative serum pregnancy test
• Use of highly effective birth control method(s) for a minimum of 60 days prior to consent and is willing to continue use for at least 12 months, or abstinence
• In good general health as determined by medical history, exams and tests

Exclusion criteria

• Acute illness or fever (≥100.4°F) within 7 days prior to dosing
• Any history of receiving treatment, vaccine, or monoclonal antibodies (mAbs) against smallpox, monkeypox, or other orthopox viruses.
• Receipt of any vaccine within 30 days prior to Screening, planned receipt of any vaccine prior to Day 1, or planned receipt of any vaccines before 45 days post-injection.
• Any medical condition for which IM injections would be contraindicated in the opinion of the investigator (eg, bleeding disorders, anticoagulant therapy, and severe thrombocytopenia)
• History of congenital or acquired immunodeficiency syndrome, , including positive human immunodeficiency virus (HIV-1/-2) antibody result
• Prior solid organ or bone marrow transplant
• Clinically significant corneal or lens abnormality as determined by history, clinical examination, or diagnostic imaging. Including, but not limited to:

• Corrected vision of less (worse) than 20/40
• History of any clinically significant history of eye trauma, in the opinion of the investigator
• History of cataracts or current cataracts
• Lens opacity greater than NC2, C2, or P0 as determined by the Lens Opacities Classification System (LOCS) III
• History of uveitis (including acute)
• Use of ocular or inhaled prescription steroids within 1 year prior to Screening nasal steroids are permissible). A single short course (ie, less than 14 days) of systemic steroid therapy is allowed provided it is concluded more than 6 months prior to Screening.
• History of diabetes
• Use of immunosuppressive agents, anticoagulants, or antiarrhythmics within 1 year prior to Screening. Nasal steroid use is permissible.
• Upper arms and thighs are with insufficient muscular tissue for IM injections or is obscured by tattoos or rash
• Use of any medications started within 30 days prior to Day -1, including prescription medications, nutritional supplements, and over-the-counter medications

• Vitamin supplements are allowed
• Recommended doses of acetaminophen are allowed, except for 24 hours prior to dosing
• Recommended doses of non-steroidal anti-inflammatory drugs (NSAIDs) (eg, aspirin, ibuprofen) are also allowed, except for 7 days prior to dosing
• Positive hepatitis B surface antigen, hepatitis B core antigen, or hepatitis C antibody
• Positive urine drug test or cotinine (indicating active current smoking) at Screening or Day -1, positive alcohol breath test at Screening or on Day -1, or suspected/known drug abuse and/or alcohol use disorder
• Smoking or has used nicotine or nicotine-containing products (eg, snuff, nicotine patch, nicotine chewing gum, mock cigarettes, or inhalers) within 3 months before study drug dosing
• Dosing in any clinical research study evaluating another investigational drug or therapy within 30 days or at least 5 half-lives (whichever is longer) of receiving the investigational drug prior to Screening
• Progressive, unstable, or uncontrolled medical conditions that have required medical attention or changes to medication for medical reasons within 90 days prior to consent
• History of allergic reactions or hypersensitivity reactions to other therapeutic antibodies or immunoglobulins
• Receipt of any mAbs in the 12 months prior to Screening
• High blood pressure
• Women who are either pregnant or breast-feeding
• Vulnerable individuals (eg, military recruits, persons in compulsory detention, those with limited legal capacity)
• Receipt of immunoglobulins or any blood products within 90 days prior to consent or planned receipt during the study period
• Donation or loss of >500 mL of blood within 30 days or plasma within 7 days of Day 1; any planned donation of blood or plasma during the study period
• History of any malignant neoplasm within the last 5 years, with the exception of adequately treated localized or in situ non-melanoma carcinoma of the skin or the cervix
• Strenuous activity or contact sports within 48 hours before study drug dosing and through Day 8

26\. History of relevant drug and/or food allergies

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

Prevention

Study locations

United States · 1 center

• PPD Las Vegas Clinical Research Unit — Las Vegas

Identifiers

NCT: NCT07595458 · DDF4-CL101 · MCDC No. W15QKN-16-9-1002

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗