Functional Cure Study of Anti-PD-L1 Antibody ASC22 in Combination With Chidamide in HIV-infected Patients With Antiviral Suppression
1 other identifier
interventional
15
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2 hiv-infections
Started Jun 2022
Shorter than P25 for phase_2 hiv-infections
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 15, 2021
CompletedFirst Posted
Study publicly available on registry
November 22, 2021
CompletedStudy Start
First participant enrolled
June 29, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 30, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
July 31, 2023
CompletedSeptember 19, 2022
September 1, 2022
1.1 years
November 15, 2021
September 15, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
HIV-1 DNA levels
Change in HIV-1 DNA levels from baseline at each cycle of treatment
52 weeks
Secondary Outcomes (3)
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
Other Outcomes (1)
Treatment-Emergent Adverse Events
52 weeks
Study Arms (1)
ASC22 group
EXPERIMENTALASC22 1mg/kg hypodermic injection Q4W+Chidamide 10mg PO BIW
Interventions
The trial group received ASC22 1mg/kg hypodermic injection Q4W and Chidamide 10mg PO BIW.
Eligibility Criteria
You may qualify if:
- People diagnosed with HIV infection.
- Age ≥18 years.
- In good general health with a body mass index ≥18.0 to \<35.0 kg/m2.
- 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.
You may not qualify if:
- 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).
- +19 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Shanghai Public Health Clinical Center
Shanghai, Shanghai Municipality, 201508, China
Related Publications (1)
Wu L, Zheng Z, Xun J, Liu L, Wang J, Zhang X, Shao Y, Shen Y, Zhang R, Zhang M, Sun M, Qi T, Wang Z, Xu S, Song W, Tang Y, Zhao B, Song Z, Routy JP, Lu H, Chen J. Anti-PD-L1 antibody ASC22 in combination with a histone deacetylase inhibitor chidamide as a "shock and kill" strategy for ART-free virological control: a phase II single-arm study. Signal Transduct Target Ther. 2024 Sep 9;9(1):231. doi: 10.1038/s41392-024-01943-9.
PMID: 39245675DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER GOV
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Deputy chief physician
Study Record Dates
First Submitted
November 15, 2021
First Posted
November 22, 2021
Study Start
June 29, 2022
Primary Completion
July 30, 2023
Study Completion
July 31, 2023
Last Updated
September 19, 2022
Record last verified: 2022-09