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Safety and Virologic Effect of a Human Monoclonal Antibody (VRC01) Administered Intravenously to Adults During Early Acute HIV Infection

This study is currently recruiting participants.
Verified September 2016 by National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor:
ClinicalTrials.gov Identifier:
NCT02591420
First Posted: October 29, 2015
Last Update Posted: October 3, 2016
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.
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
  Purpose
This study will evaluate the safety and virologic effect of an experimental human monoclonal antibody (mAb), VRC-HIVMAB060-00-AB (VRC01), alone or in combination with antiretroviral therapy (ART), in adults during early acute HIV infection.

Condition Intervention Phase
HIV Infections Biological: VRC01 Biological: Placebo for VRC01 Drug: Antiretroviral therapy (ART) (regimen will vary within countries and by patient) Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Safety and Virologic Effect of a Human Monoclonal Antibody, VRC-HIVMAB060-00-AB (VRC01), With Broad HIV-1 Neutralizing Activity, Administered Intravenously to Adults During Early Acute HIV Infection

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Number of grade 3 or greater mAb-related reactogenicity and mAb-related adverse events (AEs) [ Time Frame: Measured through Week 24 ]
  • Plasma viral load change from Day 0 to Day 7 [ Time Frame: Measured through Day 7 ]

Secondary Outcome Measures:
  • Time to virologic suppression (less than 50 copies/ml) in plasma [ Time Frame: Measured through Week 24 ]
  • Number of total viremic copy days (area under viral load curve) from Day 0 to Week 24 [ Time Frame: Measured through Week 24 ]
  • Measurement of plasma viremia including single copy HIV RNA quantification [ Time Frame: Measured through Week 24 ]
    In samples with HIV RNA less than 50 copies/ml at Day 7, Day 14, and Week 24

  • Measurement of cell-associated HIV RNA and DNA in the peripheral compartment [ Time Frame: Measured through Week 24 ]
  • Percentage of participants experiencing acute retroviral syndrome [ Time Frame: Measured through Week 24 ]
  • Percentage of participants experiencing a hospitalization [ Time Frame: Measured through Week 24 ]
  • Percentage of participants experiencing opportunistic infections [ Time Frame: Measured through Week 24 ]
  • Percentage of participants experiencing non-AIDS-related conditions [ Time Frame: Measured through Week 24 ]
  • Measurement of CD4 + T cells [ Time Frame: Measured through Week 24 ]
    Decrease from baseline to nadir, increase from nadir to Week 24, and overall change from baseline to Week 24

  • Measurement of VRC01 levels in peripheral blood [ Time Frame: Measured through Week 24 ]

Estimated Enrollment: 24
Study Start Date: April 2016
Estimated Primary Completion Date: April 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1: immediate ART and placebo infusion
Participants will start ART and will receive a single infusion of placebo at Day 0.
Biological: Placebo for VRC01
Administered as an intravenous infusion over 60 minutes using a volumetric pump
Drug: Antiretroviral therapy (ART) (regimen will vary within countries and by patient)
ART is provided by the study sites and consists of country guideline-recommended first line once-daily oral combination therapy: either efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg or efavirenz 600 mg/lamivudine 300 mg/tenofovir disoproxil fumarate 300 mg. This initial ART regimen may be adjusted or switched to an alternate regimen as clinically indicated for regimen intolerance or failure.
Experimental: Group 2: immediate ART and VRC01 infusion
Participants will start ART and receive a single infusion of VRC01 at Day 0.
Biological: VRC01
40 mg/kg of VRC01 will be administered as an intravenous infusion over 60 minutes using a volumetric pump
Other Name: VRC-HIVMAB060-00-AB
Drug: Antiretroviral therapy (ART) (regimen will vary within countries and by patient)
ART is provided by the study sites and consists of country guideline-recommended first line once-daily oral combination therapy: either efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg or efavirenz 600 mg/lamivudine 300 mg/tenofovir disoproxil fumarate 300 mg. This initial ART regimen may be adjusted or switched to an alternate regimen as clinically indicated for regimen intolerance or failure.
Experimental: Group 3: immediate VRC01 infusion and subsequent ART
Participants will receive a single infusion of VRC01 on Day 0 followed by ART initiation on Day 7.
Biological: VRC01
40 mg/kg of VRC01 will be administered as an intravenous infusion over 60 minutes using a volumetric pump
Other Name: VRC-HIVMAB060-00-AB
Drug: Antiretroviral therapy (ART) (regimen will vary within countries and by patient)
ART is provided by the study sites and consists of country guideline-recommended first line once-daily oral combination therapy: either efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg or efavirenz 600 mg/lamivudine 300 mg/tenofovir disoproxil fumarate 300 mg. This initial ART regimen may be adjusted or switched to an alternate regimen as clinically indicated for regimen intolerance or failure.

Detailed Description:

Human monoclonal antibodies (mAbs) may have the potential to treat HIV infection by preventing the spread of the virus. This study will evaluate an experimental mAB known as VRC-HIVMAB060-00-AB (VRC01). The purpose of this study is to evaluate the safety and virologic effect of VRC01, alone or in combination with ART, in adults with early acute HIV infection. Researchers will also evaluate the effect of VRC01 on the establishment of an HIV reservoir during early acute HIV infection.

This study will enroll participants from the RV 217 study who are diagnosed with early acute HIV infection. Participants will be randomly assigned to one of three groups: Group 1 will begin ART and receive a single infusion of placebo at Day 0. Group 2 will begin ART and receive a single infusion of VRC01 at Day 0. Group 3 will receive a single infusion of VRC01 on Day 0 and begin ART on Day 7. ART will vary by country and will consist of country guideline-recommended first line combination therapy: either efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg or efavirenz 600 mg/lamivudine 300 mg/tenofovir disoproxil fumarate 300 mg. This initial ART regimen may be adjusted or switched to an alternate regimen as clinically indicated for regimen intolerance or failure.

Study visits will occur at Days 0, 1, 3, 7, 10, 14, 18, 21, 25, 28, 42, 56, 84, 112, 168, and 175. Visits will include a physical examination, medical history review, and blood collection. Neurocognitive testing will take place on Day 168. Some participants may take part in optional study procedures at various time points during the study including mucosal secretion collection, rectosigmoid biopsy, lymph node biopsy, leukapheresis, and lumbar puncture.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Able and willing to complete the informed consent process
  • Passes Test of Understanding
  • 18 to 50 years of age
  • Experiencing early acute HIV-1 infection as defined by blood samples on at least two separate days positive by nucleic acid testing within 21 days of a negative nucleic acid HIV-1 test
  • No history of antiretroviral therapy for any indication
  • In general good health
  • Willing to have blood samples collected and stored
  • Able to participate for 25 weeks for study visits
  • Willing to have photo or fingerprint taken for identification purposes

Female-Specific Criteria:

  • Agrees not to become pregnant from the time of study enrollment until the last study visit. If a woman has no history of hysterectomy, tubal ligation, or menopause, she must agree to use an effective birth control method: abstinence; male or female condoms; diaphragm or cervical cap with spermicide; intrauterine device; contraceptive hormones delivered by pills, patch, injections, or vaginally; and hormonal implants under the skin; or a male partner who has previously undergone a vasectomy.
  • Negative beta-human chorionic gonadotropin (HCG) pregnancy test (urine or serum) on day of enrollment for any woman unless she is post-menopause for 24 consecutive months or has undergone a surgical procedure that precludes pregnancy

Exclusion Criteria:

  • Weight less than 46 kg or greater than 115 kg
  • Previous receipt of humanized or human monoclonal antibody whether licensed or investigational
  • Ongoing AIDS-related opportunistic infection (including oral thrush or active tuberculosis)
  • Severe acute retroviral syndrome (as defined in Appendix 1 of the protocol) or other clinical condition constituting an indication for immediate antiretroviral therapy per local country guidelines
  • Active injection drug use within previous 12 months
  • History of a severe allergic reaction with generalized urticaria, angioedema, or anaphylaxis in the 2 years prior to enrollment
  • History of chronic urticaria
  • Physical finding on examination considered indicative of significant disease such as murmur (other than functional), hepatosplenomegaly, focal neurological deficit
  • Hypertension that is not well controlled by medication
  • Positive hepatitis B surface antigen at any time in the past
  • History of hepatitis C infection
  • Untreated syphilis infection
  • Estimated glomerular filtration rate (GFR) less than 50 ml/min within the past 90 days
  • Breastfeeding
  • Pregnancy
  • Receipt of licensed vaccine or other investigational study agent within 28 days prior to enrollment or past participation in an investigational HIV vaccine study with receipt of active product
  • Current or planned participation in another interventional clinical trial during the study period
  • Chronic or recurrent use of medications that modify host immune response, e.g., oral or parenteral steroids, cancer chemotherapy
  • 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, chronic hepatitis, renal failure; OR clinically significant forms of: drug or alcohol abuse, mental illness, severe asthma, autoimmune disease, psychiatric disorders, heart disease, or cancer.
  • Study site employee
  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): NCT02591420


Locations
Kenya
Kenya Med. Research Inst./Walter Reed Project, Clinical Research Centre, Off Hospital Road. Kericho Recruiting
Kericho, Kenya, 20200
Contact: Samwel K. Chirchir, R.N., B.Sc.    254-522-030868    Samwel.Chirchir@usamru-k.org   
Tanzania
National Institute for Medical Research (NIMR)-Mbeya Medical Research Center (MMRC) Non-Network CRS Recruiting
Mbeya, Tanzania
Contact: Philipp Mann, M.D., DTM&H    255-25-2506164    pmann@mmrp.org   
Thailand
ECHO Center Non-Network CRS Recruiting
Chonburi, Thailand
Contact: Suchai Kitsiripornchai, M.D.    66-81-9150028    suchaik@hiv-th.org   
Uganda
Makerere University Walter Reed Project (MUWRP) Recruiting
Kampala, Uganda
Contact: Monica Millard, B.S.N., M.P.H., C.C.R.C., R.N.    256-312-330400    mmillard@muwrp.org   
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Study Chair: LTC Julie Ake, MD U.S. Military HIV Research Program (MHRP)/Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF)
Study Chair: Merlin Robb, MD US Military HIV Research Program
  More Information

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT02591420     History of Changes
Other Study ID Numbers: RV 398
12002 ( Registry Identifier: DAIDS-ES )
WRAIR 2166 ( Other Identifier: NIAID )
First Submitted: October 28, 2015
First Posted: October 29, 2015
Last Update Posted: October 3, 2016
Last Verified: September 2016

Additional relevant MeSH terms:
Infection
Communicable Diseases
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Antibodies
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs