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Trial record 4 of 280 for:    603

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 : Recruiting
First Posted : December 15, 2017
Last Update Posted : December 18, 2017
Sponsor:
Information provided by (Responsible Party):

Study Description
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 60 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.

Sponsoring Institute: National Institute of Allergy and Infectious Diseases


Condition or disease Intervention/treatment Phase
HIV-1 Infected Adults With Controlled Viremia Genetic: VRC-HIVAAV070-00-GT (AAV8-VRC07) Phase 1

National Institute of Allergy and Infectious Diseases (NIAID) has indicated that access to an investigational treatment associated with this study is available outside the clinical trial.  

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 60 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 Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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.
Anticipated Study Start Date : December 21, 2017
Estimated Primary Completion Date : March 1, 2019
Estimated Study Completion Date : March 1, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Group 1
5x10(10)vg/kg dose of AAV8-VRC07
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.
Experimental: Group 2
5x10(11)vg/kg dose of AAV8-VRC07
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.
Experimental: Group3
2.5x10(12) vg/kg dose of AAV8-VRC07
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.


Outcome Measures

Primary Outcome Measures :
  1. 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. ]
  2. To evaluate the pharmacokinetics of VRC07 at each dose level through 24 weeks after injection. [ Time Frame: 24 weeks ]
  3. To determine the AAV8-VRC07 dose that achieves at least 50 mcg/Ml VRC07 concentration in serum. [ Time Frame: 4 weeks post injection ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

A volunteer must meet all of the following criteria:

Able and willing to complete the informed consent process.

18 to 60 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 1.1 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 greater 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.

Evidence of pre-existing antibodies to AAV8 capsid.

Weight > 115 kg.

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.

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.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03374202


Contacts
Contact: Laura Novik, R.N. (301) 451-8715 vaccines@nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: VRC Clinic    301-451-8715    vaccines@nih.gov   
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Principal Investigator: Joseph P Casazza, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT03374202     History of Changes
Other Study ID Numbers: 180030
18-I-0030
First Posted: December 15, 2017    Key Record Dates
Last Update Posted: December 18, 2017
Last Verified: December 8, 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):
ARV Therapy
Broadly Neutralizing
Gene Transfer
Monoclonal Antibody
AAV8

Additional relevant MeSH terms:
Viremia
Virus Diseases
Sepsis
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Antibodies
Immunoglobulins
Antibodies, Blocking
Immunologic Factors
Physiological Effects of Drugs