Study to Evaluate the Safety of a Gene and Cell Therapy Product in Participants With HIV That is Well-Controlled on Antiretroviral Therapy

NCT04561258 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: AGT-HC168
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 2

Brief Summary

This is a Phase 1 study to assess the safety of a gene and cell therapy for autologous donor lymphocyte infusion in HIV+ participants with well-controlled viremia on antiretroviral therapy.

Conditions

HIV

Outcome Measures

Primary Outcomes (1)

• Assess the safety of AGT103-T in HIV+ participants with well-controlled viremia on antiretroviral therapy: adverse events

  Incidence of adverse events related to AGT103-T will be graded using NCI CTCAE (v5.0)

  Days 1 to 180 post-infusion

Study Arms (2)

Low Dose Cohort

EXPERIMENTAL

A single infusion of ≥1x10e8 and \<1x10e9 genetically modified T cells.

Biological: AGT103-T

High Dose Cohort

EXPERIMENTAL

A single infusion of ≥1x10e9 and \<5x10e9 genetically modified T cells.

Biological: AGT103-T

Interventions

AGT103-T BIOLOGICAL

An autologous, genetically modified PBMC product enriched with HIV-specific and resistant CD4 T cells

High Dose Cohort; Low Dose Cohort

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female between 18-60 years
• Documented HIV infection for ≥3 years
• Suppression of HIV to \<50 copies of viral RNA/mL plasma for ≥2 years. Participants who had intermittent, isolated episodes of detectable low-level viremia (\<500c/mL; blips) will remain eligible. Participant must have a complete antiretroviral treatment history including past and present data on resistance to antiretroviral therapy
• Agree to continue their current antiretroviral regimen during the study period unless change in treatment with antiretroviral regimen is medically indicated
• Have, in the Investigator's opinion, a fully active alternative antiretroviral regimen that can be used if resistance develops to the current antiretroviral therapy regimen
• CD4 T cell count \>400 cells/mm3
• Has adequate organ function as indicated by the following laboratory values:
• Hematocrit ≥33% or hemoglobin ≥13g/dL (males) and ≥12g/dL (females)
• Platelet count ≥150,000/mm3
• Absolute neutrophil count ≥1,500/mm3
• Serum creatinine ≤1.3 times ULN or calculated creatinine clearance (for those with creatinine \>1.3 ULN) ≥60mL/min
• Prothrombin Time or INR ≤ 1.5 times ULN
• Amylase \< 3 times ULN at the time of screening
• AST (SGOT) and ALT (SGPT): ≤ 3.0 times ULN
• Adequate venous access, per Investigator judgement, and no other contraindications for leukapheresis

You may not qualify if:

• Active viral hepatitis B or hepatitis C infection. A complete hepatitis B virus (HBV) screen (B-core antibody, HBV surface antibody, and HBV surface antigen testing) must be completed. Viral load testing will be used in questionable cases, per the discretion of the Investigator.
• The results for hepatitis B may be positive for surface antibodies against HBV but must be negative for circulating HBV surface antigen to confirm the absence of active infection and negative for HBV core antigen to excluded previous active hepatitis
• The results for hepatitis C virus (HCV) may be positive for antibodies against HCV but must be negative for HCV viral RNA in blood to confirm the absence of active infection.
• Liver disease by any cause
• Active or history (within 5 years prior to screening) of at least one acquired immune deficiency syndrome (AIDS)-defining complication
• CD4 T cell nadir of \<200 cells/mm3, if the information is available at the time of screening per medical records. If this information is unavailable, the Investigator will document this in the study source records
• Cancer or malignancy that has not been in remission for at least 5 years prior to screening, with the exception of successfully treated basal cell carcinoma of the skin
• Current diagnosis of congestive heart failure, uncontrolled angina, or arrhythmias
• Baseline prolonged QTc (Fridericia Formula) of 450 ms or more
• Any clinically significant renal, hepatic, or pulmonary disease
• History of active or latent tuberculosis, regardless of treatment history
• Asplenia
• Received high dose cytoreduction therapy within 3 months prior to screening
• Currently taking (or has taken within 6 months prior to screening) the antiretroviral drug Selzentry (Maraviroc)
• Currently using protease inhibitors, efavirenz, or zidovudine

Sponsors & Collaborators

• American Gene Technologies International Inc.: lead

Study Sites (2)

Georgetown University

Washington D.C., District of Columbia, 20007, United States

Location

Washington Health Institute

Washington D.C., District of Columbia, 20017, United States

Location

Related Publications (1)

• Pauza CD, Huang K, Bordon J. Advances in cell and gene therapy for HIV disease: it is good to be specific. Curr Opin HIV AIDS. 2021 Mar 1;16(2):83-87. doi: 10.1097/COH.0000000000000666.

  PMID: 33625039 DERIVED

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2020
• First Posted: September 23, 2020
• Study Start: October 12, 2020
• Primary Completion: August 15, 2022
• Study Completion: November 21, 2022
• Last Updated: April 12, 2023

Record last verified: 2023-04

Locations

US (2)