Safety and Tolerability of AAV8 Delivery of a Broadly Neutralizing Antibody in Adults Living With HIV: a Phase 1, Dose-escalation Trial (VRC 603)

This is an interventional treatment trial for HIV-1 Infected Adults With Controlled Viremia focused on measuring ARV Therapy, Broadly Neutralizing, Gene Transfer, Monoclonal Antibody, AAV8 Read More

• INCLUSION CRITERIA:

A volunteer must meet all of the following criteria:

• Able and willing to complete the informed consent process.
• 18 to 65 years of age.
• HIV-1 infected.
• On a stable antiretroviral regimen for greater than or equal to 3 months.
• Available for clinical follow-up through the last study visit.
• Based on history and examination, must be in general good health with no evidence of clinically significant lab abnormalities and without additional clinically significant medical conditions as per exclusion criteria.
• Willing to maintain or establish a relationship with a primary health care provider for medical management of HIV infection while participating in the study.
• Willing to have blood samples collected, stored indefinitely, and used for research purposes.
• Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.

• Laboratory tests assessing subject health will be conducted within 84 days prior to enrollment and values must meet the following criteria:

  1. White blood cell count (WBC) 2,500-12,000/mm cubed;
  2. WBC differential either within institutional normal range or accompanied by approval of the Principal Investigator (PI) or designee;
  3. Platelets = 125,000 400,000/mm cubed;
  4. Hemoglobin greater than or equal to 10.0 gm/dL;
  5. Creatinine less than or equal to 1.25 x upper limit of normal (ULN);
  6. ALT less than or equal to 1.1 x ULN;
  7. AST less than or equal to 1.1 x ULN; and,

  8. VL less than or equal to 50 copies/mL and a CD4 count greater than or equal to 300/mcL.

     Male-Specific Criteria:

• Males must agree to use condoms for all sexual activity of any reproductive potential for 52 weeks after receiving the study product.

Female-Specific Criteria:

• If a woman is sexually active with a male partner and has no history of hysterectomy, tubal ligation or menopause, she must agree to use either a prescription birth control method or a barrier birth control method from the time of study enrollment through study Week 52, or to be monogamous with a partner who has had a vasectomy.
• Negative beta-HCG (human chorionic gonadotropin) pregnancy test (urine or serum) on day of enrollment for women presumed to be of reproductive potential.

EXCLUSION CRITERIA:

A volunteer will be excluded if one or more of the following conditions apply:

• Previous receipt of monoclonal antibody whether licensed or investigational.
• Previous receipt of gene therapy product.
• Ongoing AIDS-related opportunistic infection (including oral thrush).
• Active injection drug use or active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
• A titer of pre-existing antibodies to AAV8 capsid is greater than 1:90.
• Weight > 115 kg for Group 3 subjects only.
• History of a severe allergic reaction with generalized urticaria, angioedema or anaphylaxis within the 2 years prior to enrollment that has a reasonable risk of recurrence.
• 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 liver disease such as chronic hepatitis.
• Hypertension that is not well controlled by medication.
• Woman who is breast-feeding or planning to become pregnant during the study participation.
• Receipt of any investigational study agent within 28 days prior to enrollment.
• Current infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
• Any other chronic or clinically significant medical condition that in the opinion of investigator would jeopardize the safety or rights of the volunteer, including, but not limited to: diabetes mellitus type I; OR clinically significant forms of asthma, autoimmune disease, psychiatric disorders, heart disease, or cancer.