A Study to Evaluate JL18008 in Subject With HIV Immunological Non-Responders

Официальное название

Evaluation of Pharmacokinetics, Pharmacodynamics, and Safety of JL18008 Injection in Healthy Adult Subjects / HIV Immunological Non-Responders: A Randomized, Double-Blind, Placebo-Controlled Phase I/II Clinical Study

Обзор

The Phase Ib clinical trial is an add-on study based on combination antiretroviral therapy (cART). It adopts a multicenter, randomized, double-blind, placebo-controlled, multiple-dose design to evaluate the safety and efficacy of multiple intramuscular injections of JL18008 added to cART in HIV immunological non-responders (INRs). Based on the Phase Ia clinical data, three dose groups are planned for the Phase Ib trial: 20, 40, and 70 μg/kg of JL18008. Each group is planned to enroll 10 subjects (8 receiving active drug and 2 receiving placebo). All subjects must maintain their original cART regimen unchanged. Subjects in the active treatment groups will receive JL18008 injection in addition to cART, while those in the control group will receive placebo (JL18008 injection buffer) in addition to cART. The dosing regimen is tentatively once weekly (QW) for 4 consecutive weeks, which constitutes one treatment cycle, followed by an observation/follow-up period. The study drug will be administered by intramuscular injection.

Вмешательства

• Препарат JL18008 20 μg/kg
  Participants receive JL18008 20 μg/kg by intramuscular injection once weekly for 4 weeks, in addition to their stable combination antiretroviral therapy (cART).
• Препарат Placebo (for 20 μg/kg Group)
  Participants receive placebo (JL18008 injection buffer) by intramuscular injection once weekly for 4 weeks, in addition to their stable combination antiretroviral therapy (cART).
• Препарат JL18008 40 μg/kg
  Participants receive JL18008 40 μg/kg by intramuscular injection once weekly for 4 weeks, in addition to their stable combination antiretroviral therapy (cART).
• Препарат Placebo (for 40 μg/kg Group)
  Participants receive placebo (JL18008 injection buffer) by intramuscular injection once weekly for 4 weeks, in addition to their stable combination antiretroviral therapy (cART).
• Препарат JL18008 70 μg/kg
  Participants receive JL18008 70 μg/kg by intramuscular injection once weekly for 4 weeks, in addition to their stable combination antiretroviral therapy (cART).
• Препарат Placebo (for 70 μg/kg Group)
  Participants receive placebo (JL18008 injection buffer) by intramuscular injection once weekly for 4 weeks, in addition to their stable combination antiretroviral therapy (cART).

Первичные конечные точки

• Number of Participants with Treatment-Emergent Adverse Events (TEAEs) as Assessed by DAIDS v2.1 [Срок оценки: Up to 24 weeks]
• Change from Baseline in Vital Signs: Pulse Rate (bpm) [Срок оценки: Up to 24 weeks]
• Change from Baseline in Vital Signs: Systolic and Diastolic Blood Pressure (mmHg) [Срок оценки: Up to 24 weeks]
• Change from Baseline in Hematology Parameters [Срок оценки: Up to 24 weeks]
• Change from Baseline in Serum Chemistry Parameters [Срок оценки: Up to 24 weeks]
• Change from Baseline in Coagulation Parameters [Срок оценки: Up to 24 weeks]
• Change from Baseline in ECG Parameter: QTcF Interval [Срок оценки: Up to 24 weeks]

Вторичные конечные точки (12)

• Proportion of Participants with CD4⁺ T Cell Count Increase ≥100 cells/μL from Baseline [Срок оценки: Up to 24 weeks]
• Proportion of Participants Achieving CD4⁺ T Cell Count ≥500 cells/μL [Срок оценки: Up to 24 weeks]
• Proportion of Participants with Average CD4⁺ T Cell Count Increase ≥100 cells/μL over 12 Weeks [Срок оценки: Baseline through Week 12]
• Proportion of Participants with Average CD4⁺ T Cell Count ≥500 cells/μL over 12 Weeks [Срок оценки: Baseline through Week 12]
• Proportion of Participants with Average CD4⁺ T Cell Count Increase ≥100 cells/μL over 24 Weeks [Срок оценки: Baseline through Week 24]
• Proportion of Participants with Average CD4⁺ T Cell Count ≥500 cells/μL over 24 Weeks [Срок оценки: Baseline through Week 24]
• Change from Baseline in CD4/CD8 T Cell Ratio [Срок оценки: Up to 24 weeks]
• Proportion of Participants with HIV-1 RNA <50 copies/mL [Срок оценки: Up to 24 weeks]
• Number of Participants with Clinical Events [Срок оценки: Up to 24 weeks]
• Change from Baseline in Serum Cytokine Levels (IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, IFN-γ) [Срок оценки: Up to 24 weeks]
• Change from Baseline in Lymphocyte Subset Counts (cells/μL) [Срок оценки: Up to 24 weeks]
• Peak Plasma Concentration (Cmax) - Single Dose [Срок оценки: Up to 168 hours after first dose]

Критерии участия

Критерии включения

• Age 18 to 65 years (inclusive), male or female.
• Body mass index (BMI) 18.0 to 32.0 kg/m² (inclusive); body weight ≥50.0 kg for males and ≥45.0 kg for females.
• Receiving combination antiretroviral therapy (cART) for at least 48 months, with a stable antiretroviral regimen for at least 3 months prior to enrollment.

Maintained HIV-1 RNA below 50 copies/mL for at least 36 months (the earliest test date more than 36 months before enrollment), including transient viral blips (single HIV-1 RNA measurement between 50 and 200 copies/mL after excluding laboratory error). At least two HIV-1 RNA results <50 copies/mL must be available (one may be from screening).

• Immunological non-responder criteria: CD4⁺ T cell count ≤350 cells/μL within 1 year before screening. At least three CD4⁺ T cell counts ≤350 cells/μL within 4 years before enrollment, with intervals of ≥3 months between tests (the third may be from screening).
• Willing to use effective non-pharmacological contraception with partner from screening until 3 months after study completion, and no plan for sperm/egg donation during this period.
• Able to understand and provide written informed consent, and willing to comply with all protocol-specified visits and procedures.

Критерии исключения

• Known allergy to the study drug or any of its excipients.
• Receipt of immunosuppressants, immunomodulators, or systemic cytotoxic therapy within 3 months before screening.
• Receipt of hormone therapy within 1 month before screening, except for daily doses ≤10 mg prednisone or equivalent.
• History of severe autoimmune disease requiring systemic treatment or hospitalization, or any active autoimmune disease requiring treatment (including multiple sclerosis).
• History of systemic infection (viral, bacterial, parasitic, or fungal) requiring systemic treatment and/or hospitalization, or other opportunistic infection, within 30 days before screening.
• Active tuberculosis lesion within 30 days before screening.
• Blood disorders associated with hypersplenism (e.g., thalassemia, hereditary spherocytosis, Gaucher's disease, autoimmune hemolytic anemia) or history of splenectomy.
• Chronic diarrhea.
• Severe cardiovascular disease within 6 months before screening, including myocardial infarction, unstable angina, congestive heart failure (NYHA class ≥II), or arrhythmia requiring medication.
• Uncontrolled hypertension, defined as resting systolic blood pressure >140 mmHg and/or diastolic blood pressure >90 mmHg on at least two repeated measurements on different days despite antihypertensive treatment.
• Positive hepatitis B surface antigen (HBsAg), or positive hepatitis C virus antibody (HCV-Ab) with detectable HCV-RNA, or active syphilis.
• Any of the following laboratory abnormalities at screening: hemoglobin <90 g/L; neutrophil count <1.5×10⁹/L; platelet count <100×10⁹/L; serum creatinine >1.5× upper limit of normal (ULN); alanine aminotransferase >2.5×ULN; aspartate aminotransferase >2.5×ULN; alkaline phosphatase >2.5×ULN; total bilirubin >1.5×ULN; international normalized ratio >1.5; activated partial thromboplastin time >1.5×ULN.
• Diagnosis of cancer within the screening period.
• Severe neurological or psychiatric disease, or history of seizures.
• History of drug abuse within 3 months before screening, or positive urine drug screen (including morphine, methamphetamine, ketamine, MDMA, THC, cocaine), or history of alcohol abuse.
• Participation in another clinical trial with receipt of investigational drug within 3 months before screening.
• Vaccination within 6 weeks before screening, or plan to receive any vaccination within 1 year after enrollment.
• Pregnancy, positive pregnancy test, or breastfeeding.
• Any other condition that, in the opinion of the investigator, makes the subject unsuitable for participation in this clinical study.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Peking Union Medical College Hospital — Пекин

Идентификаторы

NCT: NCT07579741 · JL18008-HV/HIV INR-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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