NCT05129189招募中2 期
Functional Cure Study of Anti-PD-L1 Antibody ASC22 in Combination With Chidamide
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- HIV-1 DNA levels
研究概览
简要总结
In HIV-infected patients, enhanced PD-1 expression of T cells correlates with T cell depletion, as evidenced by reduced virus-specific proliferative capacity and decreased cytokine expression.Targeting PD-L1 drugs to block PD-1/PD-L1 signaling may promote the secretion of antiviral cytokines and achieve HIV clearance.The mechanism of action of ASC22 is to competitively block the binding of PD-1 molecules to PD-L1 through its antigen-binding region with a high affinity for hPD-L1, thereby stimulating an innate or adaptive immune response with sustained T-cell activation.This study was conducted to evaluate whether ASC22 combined with chidamide in HIV-infected patients with antiviral suppression could shrink the viral reservoir.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •People diagnosed with HIV infection.
- •Age ≥18 years.
- •In good general health with a body mass index ≥18.0 to <35.0 kg/m
- •Able to comply with the time requirements for study visits and assessments.
- •Currently on cART for at least 24 months with two consecutive plasma HIV-1 RNA < 50 copies/ml at least 12 months apart.
- •CD4+ T-cell count ≥ 250 cells/µl (including borderline values) and CD4/CD8 < 0.9 during the screening period.
- •Agree to adhere to contraception during participation in the project and for 6 months after completion of the trial.
- •Willing to sign the informed consent form.
排除标准
- •Subjects who have had any serious acute illness within 8 weeks.
- •Subjects with a history of active autoimmune disease or autoimmune disease requiring systemic therapy.
- •Pre-treatment/exposure to any other immune checkpoint inhibitors [e.g., anti-programmed cell death protein 1 (PD-1), anti-PD-L1, anti-PD-L2, anti-CTLA4, etc.].
- •The patient has been treated with
- •Received previous treatment with other anti-submarine drugs within 30 days prior to enrollment.
- •Received radiotherapy or chemotherapy 30 days prior to screening.
- •Received immunosuppressive therapy 60 days prior to screening.
- •Treatment with immunomodulators (e.g., interleukins, interferons), hydroxyurea, or phosphonates 60 days prior to screening.
- •HIV vaccine or systemic cytotoxic chemotherapy 60 days prior to screening.
- •Prior immunoglobulin (IgG) therapy.
- •Previous blood transfusion or cell growth factor therapy 90 days prior to screening.
- •Use of rifampicin, rifabutin, etc. at the time of screening or during the planned treatment phase.
- •Laboratory tests meet the following criteria.
- •absolute neutrophil count (ANC) <1.50×109/L; hemoglobin (Hb) <105 g/L (male) or <95 g/L (female); platelets <75×10^9/μ L; international normalized ratio (INR) >1× upper limit of normal (ULN).
- •Serum alanine aminotransferase (SGPT/ALT) >1.5× upper limit of normal (ULN), serum aspartate aminotransferase (SGOT/AST) >1.5× upper limit of normal (ULN), total bilirubin, direct bilirubin >1.5× upper limit of normal (ULN), serum creatinine >1.5× upper limit of normal (ULN) × upper limit of normal value (ULN).
- •Five abnormal thyroid functions with clinical significance: tests include triiodothyronine (T3), tetraiodothyronine (T4), free triiodothyronine (FT3), free tetraiodothyronine (FT3), free tetraiodothyronine (FT4), and thyroid stimulating hormone (TSH).
- •Abnormal and clinically significant adrenaline tests, which must include at least ACTH and cortisol. Abnormal and clinically significant blood glucose and glycated hemoglobin.
- •Abnormal and clinically significant twelve-lead ECG at the time of enrollment.
- •Subjects with interstitial changes on chest CT at the time of enrollment.
- •Subjects with severe cardiac disease, symptomatic or asymptomatic arrhythmias.
- •Patients with co-infection with HBV, HCV, syphilis, etc., patients with diabetes mellitus, and patients with other liver diseases.
- •Subjects with a history of active or suspected malignancy or malignant disease (except basal cell skin cancer or in situ cervical cancer) within five years.
- •Subjects with a history of tuberculosis or active tuberculosis.
- •Subjects with psychiatric or substance abuse disorders known to interfere with study requirements.
- •Subjects who have received immunomodulation or immunosuppression within 24 weeks prior to the first dose of study drug (including any dose of IV/oral [PO] steroids, but excluding steroids by inhalation, topical, or by local injection) within 24 weeks prior to the first dose of the study drug.
- •Pregnant and lactating women, or men and women who intend to conceive a child during the study period.
- •Psychiatric patients or those whose substance abuse interferes with the conduct of the trial.
- •Histone deacetylase inhibitors, such as valproate, butyrate, and phenylbutyrate, but may be enrolled after a 28-day elution period.
- •Patients with severe cardiac insufficiency [New York Heart Association (NYHA) Cardiac Insufficiency Classification Class IV].
- •Any arterial thromboembolic event, including myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack, within 6 months prior to enrollment; normatively treated uncontrolled hypertension (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg); cardiomyopathy
- •Patients with significant QT/QTC interval during the screening period (Fridericia formula.
- •(19) Patients with a significant prolongation of the QT/QTC interval (Fridericia formula: QTcF=QT/RR0.33) during the screening period (e.g., repeated measurements showing a QTc interval >450 ms, or another risk of torsional ventricular tachycardia [TdP] [e.g., heart failure, hypokalemia, familial long QT syndrome]) or combination of drugs that may cause prolongation of the QT/QTc interval.
- •(20) Known allergy or anti-drug antibodies to drugs or excipients used in this trial.
- •(21) Those who are judged by the investigator to be unsuitable for participation in this trial.
研究组 & 干预措施
ASC22 group
Experimental
ASC22 1mg/kg hypodermic injection Q4W+Chidamide 10mg PO BIW
干预措施: ASC22 group (Drug)
结局指标
主要结局
HIV-1 DNA levels
时间窗: 52 weeks
Change in HIV-1 DNA levels from baseline at each cycle of treatment
次要结局
- CD4+ T-cell count, CD4+ T-cell percentage, CD8+ T-cell count, CD4+/CD8+ ratio(52 weeks)
- HIV gag-specific CD8+ T ratio(52 weeks)
- HIV-1 RNA(52 weeks)
研究者
Jun Chen, MD
Deputy chief physician
Shanghai Public Health Clinical Center
研究点 (1)
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