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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Low dose KL-HIV-Tri01
* Drug: Middle dose KL-HIV-Tri01
* Drug: High dose KL-HIV-Tri01


Participation Criteria
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Eligibility Criteria
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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: 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. Active viral infections, such as HBV, HCV, CMV, or other viruses that the investigator believes will affect clinical research. Any opportunistic infection in the past one year, such as tuberculosis, cryptococcosis, which is not cured after treatment. Currently treated with Immunosuppressive medications or steroids. Previous receipt of HIV vaccine, antibody or gene therapy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional Model Description: Low dose group will be administrated with 2.4×10^11 vg/kg; Middle dose group will be administrated with 8.0×10^11 vg/kg; High dose group will be administrated with 2.4×10^12 vg/kg;
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KL-HIV-Tri01 injection solution<br>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. | Drug: Low dose KL-HIV-Tri01<br>* Subjects will be dosed with single dose of KL-HIV-Tri01 at 2.4x10^11 vg/kg.<br>* Other names: rAAV vector;Drug: Middle dose KL-HIV-Tri01<br>* Subjects will be dosed with single dose of KL-HIV-Tri01 at 8.0x10^11 vg/kg.<br>* Other names: rAAV vector;Drug: High dose KL-HIV-Tri01<br>* Subjects will be dosed with single dose of KL-HIV-Tri01 at 2.4x10^12 vg/kg.<br>* Other names: rAAV vector;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and severity of AEs and SAEs | 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. | Day 0 through 52 Weeks after KL-HIV-Tri01 administration | 
| Neutralizing Antibodies Against KL-HIV-Tri01 Capsid | Anti-KL-HIV-Tri01 Capsid antibodies were analyzed by enzyme-linked immunosorbent assay (ELISA) using a vector-matched AAV capsid as the capture agent. | Day 0 through 52 Weeks after KL-HIV-Tri01 administration | 
| Inhibitors of broadly neutralizing antibodies | Inhibitors against broadly neutralizing antibodies expressed by KL-HIV-Tri01 were analyzed by enzyme-linked immunosorbent assay (ELISA) . | Day 0 through 52 Weeks after KL-HIV-Tri01 administration | 
| Cells mediated immune response against capsids and bNabs | Number of participants with T-cell response to AAV capsid and transgene products was planned to be reported. | Day 0 through 52 Weeks after KL-HIV-Tri01 administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration and titer of serum neutralizing antibodies | The serum concentration and titer of neutralizing antibodies produced by KL-HIV-Tri01 at specified time intervals for 52 weeks after dosing was determined | Day 0 through 52 Weeks after KL-HIV-Tri01 administration | 
| CD4+T, CD8+T cell count | 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 | Day 0 through 52 Weeks after KL-HIV-Tri01 administration | 
| viral load | The clinical effects of KL-HIV-Tri01 on viral load were assessed after interruption of HAART. | Day 0 through 52 Weeks after KL-HIV-Tri01 administration | 
| Time to interrupt HAART treatment | The duration of anti-HIV replication effection of the neutralizing antibodies produced by KL-HIV-Tri01were assessed after interruption of HAART. | Day 0 through 52 Weeks after KL-HIV-Tri01 administration |