Recombinant Human Interleukin-7 (JL18008) for the Treatment of HIV-Infected Immunological Non-Responders

Официальное название

A Phase I/II Study Evaluating the Safety, Tolerability, and Efficacy of JL18008 Injection in HIV-Infected Immunological Non-Responders

Обзор

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.

Вмешательства

• Препарат JL18008
  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.

Первичные конечные точки

• The safety of JL18008 [Срок оценки: 3 months]
• The safety of JL18008 [Срок оценки: 3 months]
• The safety of JL18008 [Срок оценки: 3 months]

Вторичные конечные точки (12)

• To Evaluate the Pharmacokinetics of JL18008 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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.]

Критерии участия

Критерии включения

• Age between 18 - 65 years old, male or female.
• Body Mass Index (BMI) between 18 - 32 kg/m2, body weight ≥ 50 kg in male and ≥ 45 kg in female.
• On cART for at least 36 months, on stable regimen (no drug or dose changes) for at least 3 months prior to study entry.
• Plasma HIV RNA < 50 copies/mL in last 30 months in minimum two measurements (including the screening measurement) and the two measurements should done within 6 months prior to study entry (note: patients with single blip of detectable viremia during this period will be allowed to participate if the prior and subsequent plasma HIV RNA levels are < 50 copies/mL).
• During 12 months prior to study entry, CD4+ T cell counts > 100 and ≤ 350 cells/µL measured in at least two measurements (including the screening measurement) and the interval between the two measurements should be ≥ 3 months (Note: only one time value of CD4+ T cell count > 350 during this period will be allowed to participate if the previous and subsequent CD4+ T cell count is in the range of > 100 and ≤ 350 cells/µL).
• All subjects must agree not to participate in the conception process (e.g. active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, the subject/partner must practice at least one form of barrier birth control (condoms, with or without spermicidal agent, a diaphragm or cervical cap with spermicide, an IUD, other barrier contraception, etc.), during study and 3 months after the study.
• The subject fully understands the requirements of the study and voluntarily signs the ICF.

Критерии исключения

• Prior treatment with IL-7 or IL-2.
• Allergy to JL18008 Injection components, e.g. HSA.
• Prior treatment with immunomodulatory agents such as thymosin, immunosuppressive drugs, or cytotoxic chemotherapy within 6 months prior to study entry.
• Any history of generalized psoriasis, Crohn's disease, uveitis, systemic lupus erythematosus (SLE), Hashimoto's thyroiditis or other autoimmune diseases.
• Any history of virus, bacteria, parasites or fungal infection and other opportunistic infections requiring systemic treatment and/or hospitalization within 30 days prior to study entry.
• Active tuberculosis within 30 days prior to study entry.
• Any hematologic disease associated with hypersplenism, such as thalassemia, hereditary spherocytosis, Gaucher's Disease, and autoimmune hemolytic anemia.
• History of splenectomy.
• Any gastrointestinal illness associated with chronic or intermittent diarrhea.
• Severe cardiovascular disease: myocardial infarction, unstable angina pectoris, symptomatic congestive heart failure (New York Heart Association > class II) or cardiac arrhythmia requiring medication within 6 months prior to study entry.
• Hypertension with a resting systolic blood pressure > 140 mmHg or a resting diastolic blood pressure > 90 mmHg despite adequate antihypertensive treatment.
• Hepatitis B Surface Antigen (HBs Ag) positive and/or Hepatitis C virus (HCV) antibody positive and HCV-RNA positive.
• Abnormal clinical laboratory tests results meet any of the following criteria: Hemoglobin (HGB) < 120 g/L for men and < 110 g/L for women; White blood cell (WBC) count < 3.5 × 109/L; neutrophil count (NEUT) < 1.5 × 109/L; Platelet (PLT) count < 125 × 109/L; Creatinine (Cr) > 1.1 × upper limit of normal value (ULN); Alanine aminotransferase (ALT) > 1.1 × ULN; Aspartate aminotransferase (AST) > 1.1 × ULN; Alkaline phosphatase (ALP) > 1.1 × ULN; Total bilirubin (TBIL) >1.1 × ULN; Phosphate level < 2.5 mg/dL; International normalized ratio (INR) > 1.3; Activated partial thromboplastin time (APTT) < 1.5 × ULN.
• Any history of HIV related encephalopathy.
• Diagnosis of cancer within the last 5 years prior to study entry (except skin basal cell or squamous cell carrcinomas, and cutaneous Kaposi's sarcoma not requiring systemic therapy).
• Any history of severe mental disorders or epilepsy.
• History of drug abuse (e.g. heroin, cocaine, and crystal meth, etc.) or alcohol abuse (defined as the daily regular consumption of alcohol exceeding the following standard amount: 570 ml of beer, 750 ml of light beer, 200 ml of red wine or 60 ml of liquor, each containing about 20 g of alcohol) within 3 months prior to study entry and heavy smoker (over 20 cigarettes per day for more than 3 months) within 6 months prior to study entry.
• Treatment with another study drug within 3 months prior to study entry.
• History of vaccination with live attenuated vaccine in 6 weeks prior to study entry or vaccination planed during the study and within 3 months after completion of the study.
• Pregnancy or lactation.
• History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or sponsor physician would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07443228 · JL18008

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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