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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Low dose KL-HIV-Tri01; Drug: Middle dose KL-HIV-Tri01; Drug: High dose KL-HIV-Tri01

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 Type: Interventional
• Enrollment (Estimated): 9
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Honghua He, MD; Phone Number: +86 138 2822 9695; Email: 192880@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Affiliated Hospital of Guangdong Medical University
• Investigators: Principal Investigator: Honghua He, MD, Affiliated Hospital of Guangdong Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): November 10, 2023
• Primary Completion (Estimated): August 20, 2024
• Study Completion (Estimated): September 10, 2025

Study Registration Dates

• First Submitted: October 31, 2023
• First Submitted That Met QC Criteria: October 31, 2023
• First Posted (Actual): November 7, 2023

Study Record Updates

• Last Update Posted (Actual): November 8, 2023
• Last Update Submitted That Met QC Criteria: November 5, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Urogenital Diseases; Genital Diseases; HIV Infections
• Other Study ID Numbers: CP-Tri01-001/01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No