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

Study Overview
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Brief Summary
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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.

Official Title
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Phase 1 Study to Evaluate the Safety of Genetically Modified, Autologous T Cells in Participants With HIV That is Well-Controlled on Antiretroviral Therapy

Conditions
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HIV

Intervention / Treatment
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* Biological: AGT103-T


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Total bilirubin <1.5 times the ULN range. If total bilirubin is elevated, direct bilirubin must be < 2 times the ULN range, except in participants with Gilbert's Syndrome who must have serum bilirubin <3.0 times ULN (NOTE: If participant is on an atazanavir containing therapy then a direct bilirubin should be measured instead of the total bilirubin and must be ≤ 1.0mg/dL. Also, asymptomatic elevations due to ART medications are not exclusionary when, in the opinion of the Investigator, the abnormalities are not attributable to intrinsic hepatic disease). 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 Weight (without shoes) ≥50 kilograms Has the ability to understand the study and must be willing to comply with study-required procedures and visits Written informed consent signed and dated by the study participant A negative pregnancy test for females of childbearing potential. A female participant is considered to be of childbearing potential if she is menstruating, has an intact uterus and at least 1 ovary, and is less than 2 years postmenopausal. Unless medically prescribed, a negative drug test for amphetamines; barbiturates; benzodiazepines; cocaine; methadone (Dolophine®); opiates (codeine, morphine only); phencyclidine (PCP); propoxyphene Agree to participate in the 15-year Long-Term Follow-Up study Exclusion Criteria: 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 Prior events of hemorrhagic cystitis Evidence of urinary outflow obstruction by history, enlarged prostate on physical exam, or use of medications for urinary outflow obstruction Is being treated for culture-confirmed bacteremia or had culture-confirmed bacteremia within 1 month prior to screening Has signs or symptoms of acute infectious disease History of hereditary angioedema, acquired angioedema, or idiopathic angioedema History of neurological diseases Significant laboratory values and/or chronic medical condition that in the opinion of the Investigator could impact trial participation Received another investigational drug or device within 30 days of screening Previously received any gene transfer therapy History or any features on physical examination indicative of a bleeding diathesis Use of aspirin, dipyridamole, warfarin and antithrombin inhibitors or any other medication that is likely to affect platelet function or other aspects of blood coagulation within 3 days prior to the Leukapheresis Visit Use of chronic corticosteroids, hydroxyurea, or immunomodulating agents (e.g., monoclonal antibodies, interleukin-2, interferon-alpha or gamma, granulocyte colony stimulating factors, etc.) within 30 days prior to screening (NOTE: Use of inhaled or topical steroids is not exclusionary) Currently pregnant or breast-feeding Unwilling to use acceptable methods of birth control for 6 months following the infusion of AGT103-T if sexually active with opposite sex. The following are acceptable methods of birth control: condoms (male or female) with or without a spermicidal agent, intrauterine device, diaphragm or cervical cap with spermicide, or hormonal-based contraception Active alcohol use or dependence that, in the opinion of the Investigator, would interfere with adherence to study requirements Serious illness requiring systemic treatment and/or hospitalization within 30 days prior to screening Recent vaccination or intercurrent illness within 5 weeks prior to screening (NOTE: It is recommended that participants should have completed their routine vaccinations, e.g., hepatitis A or B, pneumococcus, influenza and tetanus diphtheria booster, at least 5 weeks prior to screening for the study) Known allergy to Dimethyl Sulfoxide (DMSO) Known allergy to Cyclophosphamide

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Dose Cohort<br>A single infusion of ≥1x10e8 and <1x10e9 genetically modified T cells. | Biological: AGT103-T<br>* An autologous, genetically modified PBMC product enriched with HIV-specific and resistant CD4 T cells<br>|
| Experimental: High Dose Cohort<br>A single infusion of ≥1x10e9 and <5x10e9 genetically modified T cells. | Biological: AGT103-T<br>* An autologous, genetically modified PBMC product enriched with HIV-specific and resistant CD4 T cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |