Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04561258
Recruitment Status : Recruiting
First Posted : September 23, 2020
Last Update Posted : October 19, 2020
Sponsor:
Information provided by (Responsible Party):
American Gene Technologies International Inc.

Tracking Information
First Submitted Date  ICMJE September 14, 2020
First Posted Date  ICMJE September 23, 2020
Last Update Posted Date October 19, 2020
Actual Study Start Date  ICMJE October 12, 2020
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 22, 2020)
Assess the safety of AGT103-T in HIV+ participants with well-controlled viremia on antiretroviral therapy: adverse events [ Time Frame: Days 1 to 180 post-infusion ]
Incidence of adverse events related to AGT103-T will be graded using NCI CTCAE (v5.0)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Evaluate the Safety of a Gene and Cell Therapy Product in Participants With HIV That is Well-Controlled on Antiretroviral Therapy
Official Title  ICMJE Phase 1 Study to Evaluate the Safety of Genetically Modified, Autologous T Cells in Participants With HIV That is Well-Controlled on Antiretroviral Therapy
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HIV
Intervention  ICMJE Biological: AGT103-T
An autologous, genetically modified PBMC product enriched with HIV-specific and resistant CD4 T cells
Study Arms  ICMJE
  • Experimental: Low Dose Cohort
    A single infusion of ≥1x10e8 and <1x10e9 genetically modified T cells.
    Intervention: Biological: AGT103-T
  • Experimental: High Dose Cohort
    A single infusion of ≥1x10e9 and <5x10e9 genetically modified T cells.
    Intervention: Biological: AGT103-T
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 22, 2020)
6
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2022
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female between 18-60 years
  2. Documented HIV infection for ≥3 years
  3. 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
  4. Agree to continue their current antiretroviral regimen during the study period unless change in treatment with antiretroviral regimen is medically indicated
  5. 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
  6. CD4 T cell count >500 cells/mm3
  7. 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
  8. Adequate venous access, per Investigator judgement, and no other contraindications for leukapheresis
  9. Weight (without shoes) ≥50 kilograms
  10. Has the ability to understand the study and must be willing to comply with study-required procedures and visits
  11. Written informed consent signed and dated by the study participant
  12. 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.
  13. Unless medically prescribed, a negative drug test for amphetamines; barbiturates; benzodiazepines; cannabinoids (marijuana); cocaine; methadone (Dolophine®); opiates (codeine, morphine only); phencyclidine (PCP); propoxyphene
  14. Agree to participate in the 15-year Long-Term Follow-Up study

Exclusion Criteria:

  1. 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.
  2. Liver disease by any cause
  3. Active or history (within 5 years prior to screening) of at least one acquired immune deficiency syndrome (AIDS)-defining complication
  4. CD4 T cell nadir of <300 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
  5. 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
  6. Current diagnosis of congestive heart failure, uncontrolled angina, or arrhythmias
  7. Baseline prolonged QTc (Fridericia Formula) of 450 ms or more
  8. Any clinically significant renal, hepatic, or pulmonary disease
  9. History of active or latent tuberculosis, regardless of treatment history
  10. Asplenia
  11. Received high dose cytoreduction therapy within 3 months prior to screening
  12. Currently taking (or has taken within 6 months prior to screening) the antiretroviral drug Selzentry (Maraviroc)
  13. Currently using protease inhibitors, efavirenz, or zidovudine
  14. Prior events of hemorrhagic cystitis
  15. Evidence of urinary outflow obstruction by history, enlarged prostate on physical exam, or use of medications for urinary outflow obstruction
  16. Is being treated for culture-confirmed bacteremia or had culture-confirmed bacteremia within 1 month prior to screening
  17. Has signs or symptoms of acute infectious disease
  18. History of hereditary angioedema, acquired angioedema, or idiopathic angioedema
  19. History of neurological diseases
  20. Significant laboratory values and/or chronic medical condition that in the opinion of the Investigator could impact trial participation
  21. Received another investigational drug or device within 30 days of screening
  22. Previously received any gene transfer therapy
  23. History or any features on physical examination indicative of a bleeding diathesis
  24. 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
  25. 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)
  26. Currently pregnant or breast-feeding
  27. 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
  28. Active alcohol use or dependence that, in the opinion of the Investigator, would interfere with adherence to study requirements
  29. Serious illness requiring systemic treatment and/or hospitalization within 30 days prior to screening
  30. 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)
  31. Known allergy to Dimethyl Sulfoxide (DMSO)
  32. Known allergy to Cyclophosphamide
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Anisha Mannan 301-337-2100 clinicaltrials@americangene.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04561258
Other Study ID Numbers  ICMJE AGT-HC168
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party American Gene Technologies International Inc.
Study Sponsor  ICMJE American Gene Technologies International Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account American Gene Technologies International Inc.
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP