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

Study Overview
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Brief Summary
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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.

Detailed Description
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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 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, available first line combination therapy: currently 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.

Official Title
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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

Conditions
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HIV Infections

Intervention / Treatment
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* Biological: VRC01
* Biological: Placebo for VRC01
* Drug: Antiretroviral therapy (ART) (regimen will vary within countries and by patient)


Participation Criteria
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Eligibility Criteria
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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 OR by a positive nucleic acid test or a positive 4th generation enzyme immunoassay (EIA) in the context of a negative 2nd or negative 3rd generation HIV EIA test No history of antiretroviral therapy for any indication in the last 30 days. 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 I of the protocol) or clinical condition (other than HIV infection) 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 Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 2 times the upper limit of normal (ULN). Absolute neutrophil count (ANC) less than 740 cells/mm^3 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: immediate ART and placebo infusion<br>Participants will start ART and will receive a single infusion of placebo at Day 0. | Biological: Placebo for VRC01<br>* Administered as an intravenous infusion over 30 to 60 minutes using a volumetric pump<br>Drug: Antiretroviral therapy (ART) (regimen will vary within countries and by patient)<br>* ART is provided by the study sites and consists of country guideline-recommended, available first line once-daily oral combination therapy: currently 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.<br>|
| Experimental: Group 2: immediate ART and VRC01 infusion<br>Participants will start ART and receive a single infusion of VRC01 at Day 0. | Biological: VRC01<br>* 40 mg/kg of VRC01 will be administered as an intravenous infusion over 30 to 60 minutes using a volumetric pump<br>* Other names: VRC-HIVMAB060-00-AB;Drug: Antiretroviral therapy (ART) (regimen will vary within countries and by patient)<br>* ART is provided by the study sites and consists of country guideline-recommended, available first line once-daily oral combination therapy: currently 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.<br>|
| Experimental: Group 3: immediate VRC01 infusion and subsequent ART<br>Participants will receive a single infusion of VRC01 on Day 0 followed by ART initiation on Day 7. | Biological: VRC01<br>* 40 mg/kg of VRC01 will be administered as an intravenous infusion over 30 to 60 minutes using a volumetric pump<br>* Other names: VRC-HIVMAB060-00-AB;Drug: Antiretroviral therapy (ART) (regimen will vary within countries and by patient)<br>* ART is provided by the study sites and consists of country guideline-recommended, available first line once-daily oral combination therapy: currently 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of grade 3 or greater mAb-related reactogenicity and mAb-related adverse events (AEs) |  | Measured through Week 24 | 
| Plasma viral load change from Day 0 to Day 7 |  | Measured through Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to virologic suppression (less than 50 copies/ml) in plasma |  | Measured through Week 24 | 
| Number of total viremic copy days (area under viral load curve) from Day 0 to Week 24 |  | Measured through Week 24 | 
| Measurement of plasma viremia including single copy HIV RNA quantification | In samples with HIV RNA less than 50 copies/ml at Day 7, Day 14, and Week 24 | Measured through Week 24 | 
| Measurement of cell-associated HIV RNA and DNA in the peripheral compartment |  | Measured through Week 24 | 
| Percentage of participants experiencing acute retroviral syndrome |  | Measured through Week 24 | 
| Percentage of participants experiencing a hospitalization |  | Measured through Week 24 | 
| Percentage of participants experiencing opportunistic infections |  | Measured through Week 24 | 
| Percentage of participants experiencing non-AIDS-related conditions |  | Measured through Week 24 | 
| Measurement of CD4 + T cells | Decrease from baseline to nadir, increase from nadir to Week 24, and overall change from baseline to Week 24 | Measured through Week 24 | 
| Measurement of VRC01 levels in peripheral blood |  | Measured through Week 24 |