A Clinical Study Evaluating the Safety, Tolerability, and Effect on HIV Reservoir of Ibalizumab Combined With Chidamide (a Histone Deacetylase Inhibitor) in People Living With HIV
HIV viral reservoirs represent the major barrier to curing AIDS, and effectively reducing viral reservoirs in people living with HIV through different strategies has become a research priority in the HIV field.
Ipilimumab-tovorafenib monoclonal antibody injection (Aituo combination antibody, QL1706) contains two engineered monoclonal antibodies targeting PD-1 and CTLA-4. Chidamide is the first independently developed histone deacetylase inhibitor in China. This study aims to evaluate the safety and efficacy of Aituo combination antibody combined with chidamide in people living with HIV.
This study adopts a modified "1+3+3" dose-escalation design. Initially, one participant will be enrolled at dose level 1 (DL1) for safety observation. If the treatment is well tolerated, the study will proceed to a standard 3+3 design, with sequential dose escalation to DL2 and DL3.
Three dose levels are planned: DL1, the starting dose, consists of ipilimumab-tovorafenib monoclonal antibody injection at 0.3 mg/kg once every 4 weeks ± 1 day for a total of three doses, in combination with chidamide 10 mg orally twice weekly for 12 weeks. DL2 consists of ipilimumab-tovorafenib monoclonal antibody injection at 1 mg/kg once every 4 weeks ± 1 day for a total of three doses, in combination with chidamide 10 mg orally twice weekly for 12 weeks. DL3 consists of ipilimumab-tovorafenib monoclonal antibody injection at 2 mg/kg once every 4 weeks ± 1 day for a total of three doses, in combination with chidamide 10 mg orally twice weekly for 12 weeks.
During dose escalation, progression to the next dose level or discontinuation of escalation will be determined according to the occurrence of dose-limiting toxicities (DLTs). The DLT observation window is 28 days after the first dose. Participants evaluable for DLT are those who complete the observation window or experience a DLT. After completion of dose escalation, the maximum tolerated dose (MTD) will be determined based on safety and tolerability. If the MTD is not reached, DL3 will be selected as the dose for subsequent study.
After determination of the MTD or the subsequent study dose, an additional 11 participants will be enrolled at that dose level to further evaluate safety, tolerability, and preliminary efficacy. The maximum total sample size of the study will be 29 participants.
Studieoversikt
Status
Intervensjon / Behandling
Studietype
Registrering (Antatt)
Fase
- Fase 1
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
- Voksen
- Eldre voksen
Tar imot friske frivillige
Beskrivelse
Inclusion Criteria:
- Subjects aged 18-65 years.
- Confirmed HIV infection by both initial screening assay and Western blot (WB) confirmatory test.
- Receiving a stable ART regimen for at least 6 months.
- Viral load below the lower limit of detection.
- CD4+ T-cell count >200 cells/mm³.
- Voluntarily signed the informed consent form and able to comply with regular follow-up visits, specimen collection, and monitoring/treatment of study-related adverse events.
- Use effective contraception from 4 weeks prior to study initiation until 4 weeks after study completion.
Exclusion Criteria:
- Pregnant or breastfeeding women, or women planning to become pregnant during the study observation period.
- Subjects with poor treatment adherence.
- Receipt of immunosuppressants, other immunomodulatory agents, or cytotoxic drugs within 6 months prior to screening.
- Presence of severe underlying cardiac, cerebral, hepatic, renal, or other systemic diseases; neutrophil count <1000/mm³; platelet count <75,000/mm³; allergy to the investigational drug; or other contraindications to treatment.
- Presence of progressive (or active) malignancy, including but not limited to advanced, metastatic, or unresectable solid tumors or hematologic malignancies.
- Unwillingness to sign the informed consent form.
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: N/A
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
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Eksperimentell: Ibalizumab Combined with Chidamide
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Three dose levels are planned: DL1, the starting dose, consists of ipilimumab-tovorafenib monoclonal antibody injection at 0.3 mg/kg once every 4 weeks ± 1 day for a total of three doses, in combination with chidamide 10 mg orally twice weekly for 12 weeks.
DL2 consists of ipilimumab-tovorafenib monoclonal antibody injection at 1 mg/kg once every 4 weeks ± 1 day for a total of three doses, in combination with chidamide 10 mg orally twice weekly for 12 weeks.
DL3 consists of ipilimumab-tovorafenib monoclonal antibody injection at 2 mg/kg once every 4 weeks ± 1 day for a total of three doses, in combination with chidamide 10 mg orally twice weekly for 12 weeks.
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Number and proportion of participants with treatment-emergent adverse events as assessed by CTCAE v5.0
Tidsramme: A total of 8 study visits are planned, including Visit 1 (Week -2), Visit 2 (Week 0), Visit 3 (Week 4 ± 1 day), Visit 4 (Week 8 ± 1 day), Visit 5 (Week 12 ± 1 day), Visit 6 (Week 16 ± 1 day), Visit 7 (Week 20 ± 1 day), and Visit 8 (Week 24 ± 1 day).
|
Safety will be assessed by the incidence, severity, seriousness, and relationship to study treatment of treatment-emergent adverse events, including adverse events, serious adverse events, laboratory abnormalities, vital sign abnormalities, and physical examination findings.
Adverse events will be graded according to CTCAE v5.0.
|
A total of 8 study visits are planned, including Visit 1 (Week -2), Visit 2 (Week 0), Visit 3 (Week 4 ± 1 day), Visit 4 (Week 8 ± 1 day), Visit 5 (Week 12 ± 1 day), Visit 6 (Week 16 ± 1 day), Visit 7 (Week 20 ± 1 day), and Visit 8 (Week 24 ± 1 day).
|
|
Number and proportion of participants who discontinue or interrupt study treatment due to adverse events
Tidsramme: A total of 8 study visits are planned, including Visit 1 (Week -2), Visit 2 (Week 0), Visit 3 (Week 4 ± 1 day), Visit 4 (Week 8 ± 1 day), Visit 5 (Week 12 ± 1 day), Visit 6 (Week 16 ± 1 day), Visit 7 (Week 20 ± 1 day), and Visit 8 (Week 24 ± 1 day).
|
Tolerability will be assessed by the number and proportion of participants who discontinue, interrupt, or modify study treatment because of adverse events or clinically significant laboratory abnormalities.
|
A total of 8 study visits are planned, including Visit 1 (Week -2), Visit 2 (Week 0), Visit 3 (Week 4 ± 1 day), Visit 4 (Week 8 ± 1 day), Visit 5 (Week 12 ± 1 day), Visit 6 (Week 16 ± 1 day), Visit 7 (Week 20 ± 1 day), and Visit 8 (Week 24 ± 1 day).
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Change from baseline in HIV reservoir size as measured by total HIV DNA and CA HIV RNA
Tidsramme: A total of 8 study visits are planned, including Visit 1 (Week -2), Visit 2 (Week 0), Visit 3 (Week 4 ± 1 day), Visit 4 (Week 8 ± 1 day), Visit 5 (Week 12 ± 1 day), Visit 6 (Week 16 ± 1 day), Visit 7 (Week 20 ± 1 day), and Visit 8 (Week 24 ± 1 day).
|
Exploratory efficacy will be assessed by the change from baseline in HIV reservoir size, measured by total HIV DNA and CA HIV RNA in peripheral blood mononuclear cells at scheduled study visits.
|
A total of 8 study visits are planned, including Visit 1 (Week -2), Visit 2 (Week 0), Visit 3 (Week 4 ± 1 day), Visit 4 (Week 8 ± 1 day), Visit 5 (Week 12 ± 1 day), Visit 6 (Week 16 ± 1 day), Visit 7 (Week 20 ± 1 day), and Visit 8 (Week 24 ± 1 day).
|
Samarbeidspartnere og etterforskere
Studierekorddatoer
Studer hoveddatoer
Studiestart (Antatt)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Blodbårne infeksjoner
- Urogenitale sykdommer
- Kjønnssykdommer
- Sykdommer i immunsystemet
- Infeksjoner
- RNA-virusinfeksjoner
- Virussykdommer
- Smittsomme sykdommer
- Seksuelt overførbare sykdommer, virale
- Seksuelt overførbare sykdommer
- Lentivirus infeksjoner
- Retroviridae-infeksjoner
- Immunologiske mangelsyndromer
- Langsomme virussykdommer
- HIV-infeksjoner
- Ervervet immunsviktsyndrom
- N- (2-amino-5-fluorbenzyl) -4- (N- (pyridin-3-acryyl) aminometyl) benzamid
Andre studie-ID-numre
- HCIT-003
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
IPD-planbeskrivelse
Participant Privacy and Confidentiality:
Although data would be de-identified prior to sharing, the IPD encompass detailed clinical, virologic, and immunologic parameters. Given the specific sensitivities associated with the HIV-infected population and the nature of the medical information, a residual risk of re-identification through the triangulation of indirect identifiers persists. Public sharing of IPD may therefore contravene data protection regulations and the privacy assurances stipulated in the participant informed consent documentation.
- Limitations of Informed Consent Scope:
The informed consent form executed for this study does not explicitly authorize the disclosure of participant-level raw data to third parties or its deposition in public data repositories. The investigators are bound by legal and ethical obligations to utilize the data solely within the parameters approved in the study protocol and the corresponding informed consent.
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