JL18008 Injection is designed to improve the immune response in cART-treated HIV-infected immunological non-responders (HIV INRs). The study includes 3 trials: Phase Ia: A randomized, single-blind, placebo-controlled, single-dose escalation study to evaluate the tolerability and safety of JL18008 Injection and determine the RED in HIV INRs. Phase Ib: A randomized, double-blind, placebo-controlled, dose expansion study to evaluate the safety of JL18008 Injection and determine the RP2D in HIV INRs. Phase II: A randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of JL18008 Injection in HIV INRs.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
52
The dose escalation scheme combines eight dose cohorts 1, 2, 4, 8, 16, 30, 50, and 70 μg/kg. Four subjects will be enrolled in the first 3 dose levels, and 8 subjects will be enrolled in the rest 5 dose levels. In this study, the eligible subjects will receive a single-dose JL18008 Injection or placebo.
The safety of JL18008
Number of participants with any death.
Time frame: 3 months
The safety of JL18008
Number of participants with AEs and SAEs.
Time frame: 3 months
The safety of JL18008
Number of participants with discontinuation due to AEs.
Time frame: 3 months
To Evaluate the Pharmacokinetics of JL18008
Cmax
Time frame: Intensive PK sampling will be performed at the following time points: 0.5 hour of pre-dose and 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168 (Day 8), 240 (Day 11), 336 (Day15), 504 (Day 22), 672 (Day 29) hours of post-dose.
To Evaluate the Pharmacokinetics of JL18008
Tmax
Time frame: Intensive PK sampling will be performed at the following time points: 0.5 hour of pre-dose and 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168 (Day 8), 240 (Day 11), 336 (Day15), 504 (Day 22), 672 (Day 29) hours of post-dose.
To Evaluate the Pharmacokinetics of JL18008
AUC0-inf
Time frame: Intensive PK sampling will be performed at the following time points: 0.5 hour of pre-dose and 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168 (Day 8), 240 (Day 11), 336 (Day 15), 504 (Day 22), 672 (Day 29) hours of post-dose.
To Evaluate the Pharmacokinetics of JL18008
t1/2
Time frame: Intensive PK sampling will be performed at the following time points: 0.5 hour of pre-dose and 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168 (Day 8), 240 (Day 11), 336 (Day 15), 504 (Day 22), 672 (Day 29) hours of post-dose.
To Evaluate the Pharmacokinetics of JL18008
AUC0-t
Time frame: Intensive PK sampling will be performed at the following time points: 0.5 hour of pre-dose and 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168 (Day 8), 240 (Day 11), 336 (Day 15), 504 (Day 22), 672 (Day 29) hours of post-dose.
To Evaluate the Pharmacokinetics of JL18008
CL/F
Time frame: Intensive PK sampling will be performed at the following time points: 0.5 hour of pre-dose and 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168 (Day 8), 240 (Day 11), 336 (Day 15), 504 (Day 22), 672 (Day 29) hours of post-dose.
To Evaluate the Pharmacokinetics of JL18008
Vz/F
Time frame: Intensive PK sampling will be performed at the following time points: 0.5 hour of pre-dose and 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168 (Day 8), 240 (Day 11), 336 (Day 15), 504 (Day 22), 672 (Day 29) hours of post-dose.
To Evaluate the Efficacy of Escalating Doses of JL18008
The proportion of subjects whose CD4+ T cell count increases ≥ 100 cells/μL on D28. The proportion of subjects whose CD4+ T cell count ≥ 400 cells/μL on D28.
Time frame: The PD sampling time points are: 0.5 hour of pre-dose and 24, 48, 72, 96, 120, 168(D8), 240(D11), 336(D15), 504(D22), 672(D29), 1320(D56) and 1992(D84) hours of post-dose.
Immunogenicity
ADA on baseline, D15, and D28. Nab when ADA is positive. The proportion of subjects with ADA and/or Nab positive.
Time frame: The samples for ADA assessment will be collected at the following time points: 0.5 hour of pre-dose and 336(D15), 672(D29), 1320(D56) and 1992(D84) hours of post-dose, or the last visit if a subject withdrawal early from the study.
To Evaluate the Serum Cytokines Concentrations of Escalating Doses of JL18008
The changes in IL-2 concentrations from baseline.
Time frame: The samples will be collected at the following time points: 0.5 hour of pre-dose and 24, 48, 72, 96, 120, 168 (Day 8), 240 (Day 11), 336 (Day 15), 504 (Day 22), 672 (Day 29) hours of post-dose.
To Evaluate the Serum Cytokines Concentrations of Escalating Doses of JL18008
The changes in IL-4 concentrations from baseline.
Time frame: The samples will be collected at the following time points: 0.5 hour of pre-dose and 24, 48, 72, 96, 120, 168 (Day 8), 240 (Day 11), 336 (Day 15), 504 (Day 22), 672 (Day 29) hours of post-dose.
To Evaluate the Serum Cytokines Concentrations of Escalating Doses of JL18008
The changes in IL-6 concentrations from baseline.
Time frame: The samples will be collected at the following time points: 0.5 hour of pre-dose and 24, 48, 72, 96, 120, 168 (Day 8), 240 (Day 11), 336 (Day 15), 504 (Day 22), 672 (Day 29) hours of post-dose.
To Evaluate the Serum Cytokines Concentrations of Escalating Doses of JL18008
The changes in IL-8 concentrations from baseline.
Time frame: The samples will be collected at the following time points: 0.5 hour of pre-dose and 24, 48, 72, 96, 120, 168 (Day 8), 240 (Day 11), 336 (Day 15), 504 (Day 22), 672 (Day 29) hours of post-dose.
To Evaluate the Serum Cytokines Concentrations of Escalating Doses of JL18008
The changes in IL-10 concentrations from baseline.
Time frame: The samples will be collected at the following time points: 0.5 hour of pre-dose and 24, 48, 72, 96, 120, 168 (Day 8), 240 (Day 11), 336 (Day 15), 504 (Day 22), 672 (Day 29) hours of post-dose.
To Evaluate the Serum Cytokines Concentrations of Escalating Doses of JL18008
The changes in TNF-α concentrations from baseline.
Time frame: The samples will be collected at the following time points: 0.5 hour of pre-dose and 24, 48, 72, 96, 120, 168 (Day 8), 240 (Day 11), 336 (Day 15), 504 (Day 22), 672 (Day 29) hours of post-dose.
To Evaluate the Serum Cytokines Concentrations of Escalating Doses of JL18008
The changes in IFN-γ concentrations from baseline.
Time frame: The samples will be collected at the following time points: 0.5 hour of pre-dose and 24, 48, 72, 96, 120, 168 (Day 8), 240 (Day 11), 336 (Day 15), 504 (Day 22), 672 (Day 29) hours of post-dose.
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