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Trial record 1 of 1 for:    18-i-0030
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VRC 603: A Phase I, Dose-Escalation Study of the Safety of AAV8-VRC07 (VRC-HIVAAV070-00-GT) Recombinant AAV Vector Expressing VRC07 HIV-1 Neutralizing Antibody in Antiretroviral -Treated, HIV-1 Infected Adults With Controlled Viremia.

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ClinicalTrials.gov Identifier: NCT03374202
Recruitment Status : Active, not recruiting
First Posted : December 15, 2017
Last Update Posted : January 25, 2022
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

Tracking Information
First Submitted Date  ICMJE December 14, 2017
First Posted Date  ICMJE December 15, 2017
Last Update Posted Date January 25, 2022
Actual Study Start Date  ICMJE January 11, 2018
Estimated Primary Completion Date August 8, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 18, 2021)
  • Immune response [ Time Frame: Over 5 years of the study participation ]
    Determine the immune responses to the AAV8-VRC07 product.
  • Evaluate the pharmacokinetics [ Time Frame: 24 weeks post injection ]
    At all 3 dose levels.
  • Evaluate safety and tolerability [ Time Frame: Through 52 weeks post product administration ]
    5x10(10) vg/kg, 5x10(11) vg/kg, or 2.5x10(12) vg/kg of AAV8-VRC07 will be administered IM to HIV-1 infected adults.
  • Evaluate concentration [ Time Frame: 4 weeks post injection ]
    Determine AAV8-VRC07 dose that achieves at least 50 mcg/ml VRC07 concentration in serum
Original Primary Outcome Measures  ICMJE
 (submitted: December 14, 2017)
  • To evaluate the safety and tolerability of AAV8-VRC07 administered IM at 5x10(10) vg/kg, 5x10(11) vg/kg, or 2.5x10(12) vg/kg, to HIV-infected adults. [ Time Frame: Over 52 weeks after study injection. ]
  • To evaluate the pharmacokinetics of VRC07 at each dose level through 24 weeks after injection. [ Time Frame: 24 weeks ]
  • To determine the AAV8-VRC07 dose that achieves at least 50 mcg/Ml VRC07 concentration in serum. [ Time Frame: 4 weeks post injection ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 18, 2021)
  • To determine the serum concentration of VRC07 at specified time intervals for 1 year after injection, and if persistent, then every 6 months as long as there is detectable antibody in serum [ Time Frame: 1 year after injection ]
    The serum concentration of VRC07 at specified time intervals for 1 yr after injection will be determined.
  • To assess for potential clinical effects of the product on CD4 cell count and viral load in study participants [ Time Frame: 24 weeks post injection. ]
    The clinical effects of pAAV8-VRC07 on CD4 cell count and viral load will be assessed.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 14, 2017)
  • To assess for potential clinical effects of the product on CD4 cell count and viral load in study participants. [ Time Frame: 24 weeks post injection ]
  • To determine the serum concentration of VRC07 at specified time intervals for 1 year after injection, and if persistent, then every 6 months as long as there is detectable antibody in serum. [ Time Frame: 1 year after injection ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE VRC 603: A Phase I, Dose-Escalation Study of the Safety of AAV8-VRC07 (VRC-HIVAAV070-00-GT) Recombinant AAV Vector Expressing VRC07 HIV-1 Neutralizing Antibody in Antiretroviral -Treated, HIV-1 Infected Adults With Controlled Viremia.
Official Title  ICMJE VRC 603: A Phase 1 Dose-Escalation Study of the Safety of AAV8-VRC07 (VRC-HIVAAV070-00-GT) Recombinant AAV Vector Expressing VRC07 HIV-1 Neutralizing Antibody in Antiretroviral-Treated, HIV-1 Infected Adults With Controlled Viremia
Brief Summary

Background:

The Human Immunodeficiency Virus (HIV) attacks the immune system. Scientists have created a gene that could be transferred to the cells of people with HIV. The gene should tell the cells to make an antibody called VRC07. This antibody fights HIV. The VRC07 gene is packaged into a man-made version of a virus called AAV8.

Objectives:

To see if AAV8-VRC07 is safe. To study if it causes cells to produce the VRC07 antibody.

Eligibility:

Adults ages 18 65 who are HIV infected but in general good health and have been taking the same HIV medicine for at least 3 months

Design:

Participants will be screened in a different protocol.

Participants will get the study product on day 1. It will be injected one or more times in the upper arm or thigh using a needle. Participants weight will be measured to calculate the dose.

Women may have a pregnancy test.

For 7 days after getting the study product, participants will check their temperature with a thermometer. They will note any symptoms in an electronic or paper diary.

Participants will have study visits. At each one, they will have a physical exam and medical history. They will have blood drawn and may have saliva collected.

The visit schedule will be:

For 12 weeks: 1 visit a week

For the next 12 weeks: 1 visit every other week

Then about 1 visit a month

After 1 year in the study: a visit every 6 months for the next 4 years.

Total study participation is 5 years.

Detailed Description

Design: This is a Phase I study of the safety and tolerability of AAV8-VRC07 (VRC-HIVAAV070-00-GT) expressing VRC07 human monoclonal antibody with broad HIV-1 neutralizing activity in HIV-1 infected adults. It is a dose-escalation study to examine pharmacokinetics of VRC07 expression following intramuscular (IM) administration of AAV8-VRC07 in subjects on anti-retroviral therapy (ARV). The hypotheses are: 1) AAV8-VRC07 will be safe for human administration and will not elicit hypersensitivity or anti-drug antibody (ADA) to VRC07; and 2) intramuscular delivery of AAV8-VRC07 will result in production of biologically active VRC07 antibody at a concentration in serum that is measurable and safe.

Description: AAV8-VRC07 was developed by VRC, NIAID, NIH, and manufactured by the Clinical Vector Core, Center for Cellular and Molecular Therapeutics, The Children s Hospital of Philadelphia (CHOP), Philadelphia, PA. It is composed of an AAV8 recombinant vector expressing genes encoding the heavy and light chains of the VRC07 monoclonal antibody. AAV8-VRC07 will be supplied at 2.84x1013 vg/mL.

Subjects: HIV-1 infected adult volunteers (18 to 65 years old) on a stable antiretroviral regimen for more than or equal to 3 months, with controlled viremia, under the care of a physician, and without additional clinically significant medical conditions.

Study Plan: There are 3 dose escalation groups. Sequentially enrolled subjects will be assigned to the dosage level being evaluated at the time of enrollment. All injections will be administered intramuscularly (IM) by needle and syringe. Cumulative safety data will be reviewed weekly by a Protocol Safety Review Team (PSRT) that includes an Independent Safety Monitor (ISM) while injections are being administered. Safety, including reactogenicity and unsolicited AEs, laboratory findings, pharmacokinetics, and VRC07 antibody levels in blood will be assessed after the injection and summarized for an interim analysis at 4 weeks post injection. The second subject in each dose group will be injected after the 4 weeks safety assessment for the first subject. Decisions regarding dose escalation and subject enrollments will be based on safety data and the VRC07 concentration in blood at 4 weeks after product administration. The pharmacokinetics of VRC07 at each dose level will be evaluated to determine the dose that would result in antibody production that achieves at least 50 mcg/mL VRC07 concentration in serum at 4 weeks post injection with a target set point of more than or equal to 5 mcg/mL at 12 weeks post injection.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HIV-1 Infected Adults With Controlled Viremia
Intervention  ICMJE Genetic: VRC-HIVAAV070-00-GT (AAV8-VRC07)
AAV8-VRC07 is a recombinant AAV vector expressing a HIV-1 CD4 binding site-specific neutralizing antibody, VRC07
Study Arms  ICMJE
  • Experimental: Group 1
    5 x 10 (10) vg/kg IM
    Intervention: Genetic: VRC-HIVAAV070-00-GT (AAV8-VRC07)
  • Experimental: Group 2
    5 x 10 (11) vg/kg IM
    Intervention: Genetic: VRC-HIVAAV070-00-GT (AAV8-VRC07)
  • Experimental: Group3
    2.5 x 10 (12) vg/kg IM
    Intervention: Genetic: VRC-HIVAAV070-00-GT (AAV8-VRC07)
Publications *

*   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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: November 18, 2021)
9
Original Estimated Enrollment  ICMJE
 (submitted: December 14, 2017)
25
Estimated Study Completion Date  ICMJE March 1, 2027
Estimated Primary Completion Date August 8, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03374202
Other Study ID Numbers  ICMJE 180030
18-I-0030
Has Data Monitoring Committee Not Provided
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 Not Provided
Responsible Party National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )
Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Joseph P Casazza, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date November 19, 2021

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