Safety and Efficacy Clinical Study of KL-HIV-Tri01 in the Treatment of HIV Infected Subjects

Early Phase 1

Not yet recruiting

• Conditions: HIV Infections
• Interventions: Drug: Low dose KL-HIV-Tri01; Drug: Middle dose KL-HIV-Tri01; Drug: High dose KL-HIV-Tri01

• Registration Number: NCT06117657
• Lead Sponsor: Affiliated Hospital of Guangdong Medical University

Brief Summary

This is an open- label, non- randomized, uncontrolled, dose-escalation pilot study to evaluate the safety and efficacy of KL-HIV-Tri01 injection solution in HIV infected subjects treated with HAART.

Detailed Description

This is an open- label, non- randomized, uncontrolled, dose-escalation pilot study to evaluate the safety and efficacy of KL-HIV-Tri01 injection solution expressing triple targets antibodies with broad HIV-1 neutralizing activity in HIV-1 infected adults on anti-retroviral therapy (ARV). Nine subjects will be enrolled and administered with three different doses of KL-HIV-Tri01. Subjects will provide informed consent and then undergo screening assessments up to 1 month prior administration of KL-HIV-Tri01. All subjects will undergo 52 weeks safety observation and will be encouraged to enroll in an extension study to evaluate long- term safety of KL-HIV-Tri01 for total 5 years.

Study Timeline

• Study First Submitted: 2023-10-31
• Study First Submitted QC: 2023-10-31
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-05
• Study First Posted: 2023-11-07
• Last Update Posted: 2023-11-08
• Study Start: 2023-11-10
• Primary Completion: 2024-08-20
• Study Completion: 2025-09-10

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 9

Inclusion Criteria

1.18 (not inclusive) to 80 (inclusive) years of age, both male and female.

2. Conform to the Chinese AIDS Diagnosis and Treatment Guidelines (2021), HIV positive, and received HAART treatment for ≥ 3 months before enrollment.

3. CD4+T cell count≥500 cells/μl.

4. On a stable antiretroviral regimen before enrollment and viral load less than 40 copies/mL in two consecutive tests one year prior to enrollment.

5. Willing to fully understand the purpose, nature, method, and potential adverse reactions that may occur during the discontinuation period of the experiment, voluntarily participate in this experiment and sign an informed consent form.

Exclusion Criteria

1. Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with IM injections or blood draws.
2. Active viral infections, such as HBV, HCV, CMV, or other viruses that the investigator believes will affect clinical research.
3. Any opportunistic infection in the past one year, such as tuberculosis, cryptococcosis, which is not cured after treatment.
4. Currently treated with Immunosuppressive medications or steroids.
5. Previous receipt of HIV vaccine, antibody or gene therapy.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
KL-HIV-Tri01 injection solution	High dose KL-HIV-Tri01	Subjects will be dosed with three different dose of KL-HIV-Tri01 injection solution at 2.4x10\^11 vg/kg to 2.4x10\^12 vg/kg.
KL-HIV-Tri01 injection solution	Low dose KL-HIV-Tri01	Subjects will be dosed with three different dose of KL-HIV-Tri01 injection solution at 2.4x10\^11 vg/kg to 2.4x10\^12 vg/kg.
KL-HIV-Tri01 injection solution	Middle dose KL-HIV-Tri01	Subjects will be dosed with three different dose of KL-HIV-Tri01 injection solution at 2.4x10\^11 vg/kg to 2.4x10\^12 vg/kg.

Primary Outcome Measures

Name	Time	Method
Number and severity of AEs and SAEs	Day 0 through 52 Weeks after KL-HIV-Tri01 administration	AEs and SAEs from the date of product administration will be recorded through the last study visit. The relationship between AEs and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol.
Neutralizing Antibodies Against KL-HIV-Tri01 Capsid	Day 0 through 52 Weeks after KL-HIV-Tri01 administration	Anti-KL-HIV-Tri01 Capsid antibodies were analyzed by enzyme-linked immunosorbent assay (ELISA) using a vector-matched AAV capsid as the capture agent.
Inhibitors of broadly neutralizing antibodies	Day 0 through 52 Weeks after KL-HIV-Tri01 administration	Inhibitors against broadly neutralizing antibodies expressed by KL-HIV-Tri01 were analyzed by enzyme-linked immunosorbent assay (ELISA) .
Cells mediated immune response against capsids and bNabs	Day 0 through 52 Weeks after KL-HIV-Tri01 administration	Number of participants with T-cell response to AAV capsid and transgene products was planned to be reported.

Secondary Outcome Measures

Name	Time	Method
Concentration and titer of serum neutralizing antibodies	Day 0 through 52 Weeks after KL-HIV-Tri01 administration	The serum concentration and titer of neutralizing antibodies produced by KL-HIV-Tri01 at specified time intervals for 52 weeks after dosing was determined
CD4+T, CD8+T cell count	Day 0 through 52 Weeks after KL-HIV-Tri01 administration	The clinical effects of KL-HIV-Tri01 on CD4+T and CD8+T cell count were assessed. CD4+T and CD8+T Cell Count (cells/mL) shown as reported by the Clinical Center serology lab
viral load	Day 0 through 52 Weeks after KL-HIV-Tri01 administration	The clinical effects of KL-HIV-Tri01 on viral load were assessed after interruption of HAART.
Time to interrupt HAART treatment	Day 0 through 52 Weeks after KL-HIV-Tri01 administration	The duration of anti-HIV replication effection of the neutralizing antibodies produced by KL-HIV-Tri01were assessed after interruption of HAART.