HIV InfectionsPhase 2NCT02568215
Evaluating the Safety and Efficacy of the VRC01 Antibody in Reducing Acquisition of HIV-1 Infection in Women
A Phase 2 study testing VRC01 in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 21 sites in 7 countries.
Trial summary
This study will evaluate the safety and efficacy of the human monoclonal antibody (mAb) VRC-HIVMAB060-00-AB (VRC01) in preventing HIV-1 infection in high-risk, HIV-uninfected women. Read more about this study
- Who is it for?
- Ages 18 to 50 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- HIV Infections
- What is being tested?
- VRC01
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,924 participants
- Where
- 21 sitesin 7 countries
- Study dates
- May 2016to 3 Mar 2021
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- General and Demographic Criteria
- Age of 18 to 50 years
- Access to a participating clinical research site (CRS) and willingness to be followed for the planned duration of the study
- Ability and willingness to provide informed consent
- Assessment of understanding: volunteer demonstrates understanding of this study and completes a questionnaire prior to first infusion with verbal demonstration of understanding of all questionnaire items answered incorrectly
- Agrees not to enroll in another study of an investigational research agent for the duration of the participant's trial participation
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- Good general health as shown by medical history, physical exam, and screening laboratory tests
- HIV-Related Criteria
- Willingness to receive HIV test results
- Willingness to discuss HIV infection risks and amenable to HIV risk reduction counseling
- Persons born Female (assigned female sex at birth) and identifying as a female, who, in the 6 months prior to randomization, has had vaginal and/or anal intercourse with a male partner
- All volunteers who have been in a monogamous relationship with an HIV-1 seronegative partner for greater than 1 year are excluded.
- Laboratory Inclusion Values+
- Hematology
- Hemoglobin (Hgb) greater than or equal to 10.5 g/dL for volunteers who were born female, greater than or equal to 13.0 g/dL for volunteers who were born male
- Platelets greater than or equal to 100,000 cells/mm^3
- Chemistry
- Alanine aminotransferase (ALT) less than 2.5 times the institutional upper limit of normal and creatinine less than or equal to 1.25 times the institutional upper limit of normal
- Virology
- HIV uninfected, as defined in the study specific procedures (SSP), within 30 days prior to enrollment
- Urine
- Negative, trace, or 1+ urine protein by dipstick
- Reproductive Status
- Volunteers capable of becoming pregnant: negative serum or urine beta human chorionic gonadotropin (β-HCG) pregnancy test performed at the screening visit and prior to infusion on the day of initial infusion. Persons who are NOT capable of becoming pregnant due to having undergone total hysterectomy or bilateral oophorectomy (verified by medical records) are not required to undergo pregnancy testing.
- Reproductive status: A volunteer who is capable of becoming pregnant must agree to consistently use effective contraception (see the protocol and SSP for more information) for sexual activity that could lead to pregnancy from at least 21 days prior to enrollment through the last required protocol clinic visit.
- Volunteers capable of becoming pregnant must also agree not to seek pregnancy through alternative methods, such as artificial insemination or in vitro fertilization until after the last required protocol clinic visit
Who cannot join
- General
- Investigational research agents received within 30 days before first infusion
- Body mass index (BMI) greater than or equal to 40
- Pregnant or breastfeeding
- Any reactive, indeterminate, or positive HIV test, even if subsequent testing indicates that the individual is not HIV infected.
- Monoclonal antibodies and vaccines
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- Previous receipt of humanized or human monoclonal antibodies (mAbs), whether licensed or investigational
- HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received control/placebo in an HIV vaccine trial, the HVTN 703/HPTN 081 Protocol Safety Review Team (PSRT) will determine eligibility on a case-by-case basis.
- Immune System
- Serious adverse reactions to VRC01 formulation components such as sodium citrate, sodium chloride, and L-arginine hydrochloride, including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain.
- Autoimmune disease, including Type I diabetes mellitus (Not excluded from participation: Volunteer with mild, stable and uncomplicated autoimmune disease that does not require consistent immunosuppressive medication and that, in the judgment of the site investigator, is likely not subject to exacerbation and likely not to complicate reactogenicity and adverse event (AE) assessments)
- Immunodeficiency syndrome
- Clinically significant medical conditions
- Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health. A clinically significant condition or process includes but is not limited to:
- Any contraindication to repeated infusions or blood draws, including inability to establish venous access;
- A condition that requires active medical intervention or monitoring to avert grave danger to the volunteer's health or well-being during the study period; or
- A condition or process for which signs or symptoms could be confused with reactions to VRC01.
- Any medical, psychiatric, occupational, or other condition that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence, assessment of safety or infusion reactions, or a volunteer's ability to give informed consent
- Psychiatric condition that precludes compliance with the protocol. Specifically excluded are persons with psychoses within the past 3 years, ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years.
- Asthma, other than mild, well-controlled asthma
- Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions)
- Malignancy (Not excluded from participation: Volunteer who has had malignancy excised surgically and who, in the investigator's estimation, has a reasonable assurance of sustained cure. or who is unlikely to experience recurrence of malignancy during the period of the study)
- Seizure disorder: History of seizure(s) within past three years. Also exclude if volunteer has used medications in order to prevent or treat seizure(s) at any time within the past 3 years.
- History of hereditary angioedema, acquired angioedema, or idiopathic angioedema
- History of organ or tissue transplantation
- Known hepatic or renal dysfunction
Trial locations and contacts
21 sites in 7 countries.
21 sites in 7 countries
South Africa12 sites
Groote Schuur HIV CRS
Cape Town, Western Cape, 7925
Chatsworth CRS
Chatsworth, KwaZulu-Natal, 4030
Botha's Hill CRS
Durban, KwaZulu-Natal, 3660
CAPRISA eThekwini CRS
Durban, KwaZulu-Natal, 4013
Vulindlela CRS
Durban, KwaZulu-Natal, 4013
The Aurum Institute Tembisa Clinical Research Centre CRS
Johannesburg, Gauteng, 1632
Soweto HVTN CRS
Johannesburg, Gauteng, 1862
Ward 21 CRS
Johannesburg, Gauteng, 2001
Wits Reproductive Health and HIV Institute CRS (WRHI CRS)
Johannesburg, Gauteng, 2038
Aurum Institute Klerksdorp CRS
Klerksdorp, North West, 2571
Synexus Stanza Clinical Research Centre CRS
Pretoria, Gauteng, 0122
Rustenburg CRS
Rustenburg, North West, 0300
Zimbabwe3 sites
Seke South CRS
Chitungwiza
Milton Park CRS
Harare
Spilhaus CRS
Harare
Mozambique1 site
Polana Canico Health Research and Training Center (CISPOC), National Institute of Health (INS) CRS
Maputo
Tanzania1 site
National Institute for Medical Research (NIMR) - Mbeya Medical Research Center (MMRC) Network CRS
Mbeya
About this study
Official title: A Phase 2b Study to Evaluate the Safety and Efficacy of VRC01 Broadly Neutralizing Monoclonal Antibody in Reducing Acquisition of HIV-1 Infection in Women in Sub-Saharan Africa
This study will evaluate the safety and efficacy of the human monoclonal antibody (mAb) VRC-HIVMAB060-00-AB (VRC01) in preventing HIV-1 infection in high-risk, HIV-uninfected women.
Read the detailed description
This study will evaluate the safety, tolerability, and efficacy of the VRC01 antibody in preventing HIV-1 infection in healthy women at high risk of HIV infection.
Participants will be enrolled from a cohort of heterosexual women in sub-Saharan Africa. An equal number of study participants will be randomized to receive VRC01 mAb by IV infusion at a dose of 10 mg/kg or 30 mg/kg every 8 weeks, or to receive control infusions every 8 weeks. All participants will receive the VRC01 antibody or placebo by intravenous infusion at Weeks 0 (study entry), 8, 16, 24, 32, 40, 48, 56, 64, and 72. For 3 days following each infusion, participants will be asked to record and report any symptoms to study researchers.
In addition to the infusion visits, participants will attend study visits at Weeks 4, 8 + 5 days, 12, 20, 28, 36, 44, 52, 60, 68, 76, 80, 84, 88, and 92. All study visits will include blood collection and HIV testing and counseling. Select study visits will include a medical history review, physical exam, urine collection, pregnancy testing for participants capable of becoming pregnant, risk reduction counseling, and an interview/questionnaire.
- Conditions
- HIV Infections
- Being tested
- VRC01, Placebo for VRC01
- Keywords
- HIV-1 Infections
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VRC01Biological
Also called Human monoclonal antibody (mAb) VRC-HIVMAB060-00-AB
Administered by IV infusion; total dose will vary based on participant's weight
Placebo for VRC01Biological
Sodium Chloride for Injection USP, 0.9%; administered by IV infusion
| Study group | Role | What they receive |
|---|---|---|
| Group 1: Low-Dose VRC01 | Experimental | Participants will receive an IV infusion of 10 mg/kg of VRC01 over about 30 to 60 minutes at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, and 72. Receives: Biological: VRC01 |
| Group 2: High-Dose VRC01 | Experimental | Participants will receive an IV infusion of 30 mg/kg of VRC01 over about 30 to 60 minutes at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, and 72. Receives: Biological: VRC01 |
| Group 3: Placebo for VRC01 | Placebo comparator | Participants will receive an IV infusion of placebo for VRC01 over about 30 to 60 minutes at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, and 72. Receives: Biological: Placebo for VRC01 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Pain and/or Tenderness
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [July 2017]. The maximum grade observed for each symptom over the time frame is presented
Measured: Measured through 3 days after each infusion at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, 72.
Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Erythema and/or Induration
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [July 2017]. The maximum grade observed for each symptom over the time frame is presented
Measured: Measured through 3 days after each infusion at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, 72.
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [July 2017]. The following symptoms are considered as systemic reactogenicity if the onset date was within the periods of assessment specified in the protocol: malaise and/or fatigue, myalgia, headache, nausea, vomiting, chills, arthralgia, and body temperature. The item Max. Systemic Symptoms is the maximum of the individual systemic reactogenicities excluding body temperature for a participant.
Measured: Measured through 3 days after each infusion at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, 72.
Chemistry and Hematology Laboratory Measures - Alanine Aminotransferase (ALT)
For each local laboratory measure, summary statistics are presented by treatment group and timepoint.
Measured: Measured at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, 72.
Chemistry and Hematology Laboratory Measures - Creatinine
For each local laboratory measure, summary statistics are presented by treatment group and timepoint.
Measured: Measured at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, 72.
Chemistry and Hematology Laboratory Measures - Hemoglobin
For each local laboratory measure, summary statistics are presented by treatment group and timepoint.
Measured: Measured at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, 72.
Chemistry and Hematology Laboratory Measures - Lymphocyte Count, Neutrophil Count
For each local laboratory measure, summary statistics are presented by treatment group and timepoint.
Measured: Measured at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, 72.
Chemistry and Hematology Laboratory Measures - Platelets, White Blood Cells (WBC)
For each local laboratory measure, summary statistics are presented by treatment group and timepoint.
Measured: Measured at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, 72.
Chemistry and Hematology Laboratory Measures Meeting Grade 3 AE Criteria or Above
The number (percentage) of participants with chemistry and hematology laboratory measures meeting grade 3 AE criteria or above as specified in the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 [July 2017] is tabulated by treatment group and timepoint. Excludes measures taken prior to exposure to study product at Week 0/Infusion 1.
Measured: Measured at Weeks 8, 16, 24, 32, 40, 48, 56, 64, 72.
Number of Participants With Early Infusion Discontinuation and Reasons for Discontinuation
The number (percentage) of participants with early permanent discontinuation of infusions and their reason for discontinuation is summarized by treatment group. Includes all discontinuations documented on a study case report form.
Measured: Measured through Week 72 (the last infusion visit).
Incidence Rate of Early Infusion Discontinuation
Incidence rate (95% CI) of early infusion discontinuation per 100 person years. Includes discontinuations documented on a study case report form and operational discontinuations defined as 20 consecutive weeks without participant contact. Discontinuations due to pregnancy, death, or HIV-1 infection are right-censored.
Measured: Measured through Week 72 (the last infusion visit).
Number of Participants With Documented HIV-1 Infection by the Week 80 Visit
Prevention efficacy (PE) is measured as 1 minus the ratio (VRC01:control) of cumulative incidences of HIV-1 infection diagnosis between enrollment and the week 80 visit for assessment of the primary efficacy end point. Cumulative incidence was estimated with the Nelson-Aalen estimator for the cumulative hazard function, with stratification according to VRC01 dose and trial.
Measured: Measured through Week 80.
Secondary outcomes (3)
Serum Concentration of VRC01 in Participants Assigned to Receive the mAb
The pharmacokinetic analyses of VRC01 involved a subgroup of VRC01 recipients who had not acquired HIV-1 infection through the week 88 visit and were not likely to have used preexposure prophylaxis (on the basis of self-report or testing of dried blood-spot samples), randomly sampled among the trials and dose groups. Midpoint and trough concentrations are the participant-level median concentrations at the 4-week and 8-week postinfusion visits, respectively, across all 10 infusion intervals.
Measured: Day 61 (5 days post infusion #2), Midpoint (4-weeks post infusion visits): Weeks 4, 12, 16, 28, 36, 44, 52, 60, 68, 76 and Trough (infusion visits): Pre dose at Weeks 0 (study entry), 8, 16, 24, 32, 40, 48, 56, 64, and 72.
VRC01 Clinical Lot Neutralization of Founder Viruses (IC80)
The VRC01 80% inhibitory concentration (IC80) of acquired isolates was measured with the TZM-bl assay using the earliest available post-HIV-infection serum sample. Median and IQR are summarized immediately below, then the analysis of prevention efficacy was repeated for each of three prespecified categories of in vitro susceptibility of the infecting strain (IC80 less than 1 μg per milliliter, 1 to 3 μg per milliliter, or >3 μg per milliliter) with the use of the Aalen-Johansen estimator.
Measured: Measured through Week 80.
VRC01 Serum Neutralization of Autologous Founder Viruses (ID50, ID80)
Autologous titer (ID50, ID80) summaries, based on most sensitive virus, for first RNA+ samples from a subset of HIV-infected VRC01 recipients. Values below the limit of detection (less than 10) were set to NA. Summaries are only computed for the Pooled VRC01 arm.
Measured: First RNA+ Sample detected from baseline up to Week 104.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2015 (estimated)
- Study startMay 2016
- Primary completion3 Mar 2021
- Study completion3 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,924 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Lawrence Corey, Study chair, HVTN; FHCRCMyron Cohen, Study chair, HPTN; University of North Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02568215
- Sponsor's protocol ID
- HVTN 703/HPTN 081
- Other IDs
- 12045
- Status last verified
- Feb 2022
- First submitted
- 1 Oct 2015
- Last updated
- 23 Feb 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Edupuganti S, Mgodi N, Karuna ST, Andrew P, Rudnicki E, Kochar N, deCamp A, De La Grecca R, Anderson M, Karg C, Tindale I, Greene E, Broder GB, Lucas J, Hural J, Gallardo-Cartagena JA, Gonzales P, Frank I, Sobieszczyk M, Gomez Lorenzo MM, Burns D, Anderson PL, Miner MD, Ledgerwood J, Mascola JR, Gilbert PB, Cohen MS, Corey L; HVTN 704/HPTN 085 study group. Feasibility and Successful Enrollment in a Proof-of-Concept HIV Prevention Trial of VRC01, a Broadly Neutralizing HIV-1 Monoclonal Antibody. J Acquir Immune Defic Syndr. 2021 May 1;87(1):671-679. doi: 10.1097/QAI.0000000000002639.
PubMed 33587505Mgodi NM, Takuva S, Edupuganti S, Karuna S, Andrew P, Lazarus E, Garnett P, Shava E, Mukwekwerere PG, Kochar N, Marshall K, Rudnicki E, Juraska M, Anderson M, Karg C, Tindale I, Greene E, Luthuli N, Baepanye K, Hural J, Gomez Lorenzo MM, Burns D, Miner MD, Ledgerwood J, Mascola JR, Donnell D, Cohen MS, Corey L; HVTN 703/HPTN 081 Team. A Phase 2b Study to Evaluate the Safety and Efficacy of VRC01 Broadly Neutralizing Monoclonal Antibody in Reducing Acquisition of HIV-1 Infection in Women in Sub-Saharan Africa: Baseline Findings. J Acquir Immune Defic Syndr. 2021 May 1;87(1):680-687. doi: 10.1097/QAI.0000000000002649.
PubMed 33587510Huang Y, Naidoo L, Zhang L, Carpp LN, Rudnicki E, Randhawa A, Gonzales P, McDermott A, Ledgerwood J, Lorenzo MMG, Burns D, DeCamp A, Juraska M, Mascola J, Edupuganti S, Mgodi N, Cohen M, Corey L, Andrew P, Karuna S, Gilbert PB, Mngadi K, Lazarus E. Pharmacokinetics and predicted neutralisation coverage of VRC01 in HIV-uninfected participants of the Antibody Mediated Prevention (AMP) trials. EBioMedicine. 2021 Feb;64:103203. doi: 10.1016/j.ebiom.2020.103203. Epub 2021 Jan 23.
PubMed 33493795Huang Y, Zhang L, Eaton A, Mkhize NN, Carpp LN, Rudnicki E, DeCamp A, Juraska M, Randhawa A, McDermott A, Ledgerwood J, Andrew P, Karuna S, Edupuganti S, Mgodi N, Cohen M, Corey L, Mascola J, Gilbert PB, Morris L, Montefiori DC. Prediction of serum HIV-1 neutralization titers of VRC01 in HIV-uninfected Antibody Mediated Prevention (AMP) trial participants. Hum Vaccin Immunother. 2022 Dec 31;18(1):1908030. doi: 10.1080/21645515.2021.1908030. Epub 2021 Jul 2.
PubMed 34213402Corey L, Gilbert PB, Juraska M, Montefiori DC, Morris L, Karuna ST, Edupuganti S, Mgodi NM, deCamp AC, Rudnicki E, Huang Y, Gonzales P, Cabello R, Orrell C, Lama JR, Laher F, Lazarus EM, Sanchez J, Frank I, Hinojosa J, Sobieszczyk ME, Marshall KE, Mukwekwerere PG, Makhema J, Baden LR, Mullins JI, Williamson C, Hural J, McElrath MJ, Bentley C, Takuva S, Gomez Lorenzo MM, Burns DN, Espy N, Randhawa AK, Kochar N, Piwowar-Manning E, Donnell DJ, Sista N, Andrew P, Kublin JG, Gray G, Ledgerwood JE, Mascola JR, Cohen MS; HVTN 704/HPTN 085 and HVTN 703/HPTN 081 Study Teams. Two Randomized Trials of Neutralizing Antibodies to Prevent HIV-1 Acquisition. N Engl J Med. 2021 Mar 18;384(11):1003-1014. doi: 10.1056/NEJMoa2031738.
PubMed 33730454Weiner JA, Banks LA, Natarajan H, Lin S, Sami S, Kovacikova G, Carpenter MC, Ackerman ME. Drawing a line in the sand: impact of analytical choices on anti-drug antibody cut-points and testing outcomes. Bioanalysis. 2026 Jun-Jun;18(8-9):711-722. doi: 10.1080/17576180.2026.2698615. Epub 2026 Jul 14.
PubMed 42444466Reeves DB, Mayer BT, deCamp AC, Huang Y, Zhang B, Carpp LN, Magaret CA, Juraska M, Gilbert PB, Montefiori DC, Bar KJ, Cardozo-Ojeda EF, Schiffer JT, Rossenkhan R, Edlefsen P, Morris L, Mkhize NN, Williamson C, Mullins JI, Seaton KE, Tomaras GD, Andrew P, Mgodi N, Ledgerwood JE, Cohen MS, Corey L, Naidoo L, Orrell C, Goepfert PA, Casapia M, Sobieszczyk ME, Karuna ST, Edupuganti S. High monoclonal neutralization titers reduced breakthrough HIV-1 viral loads in the Antibody Mediated Prevention trials. Nat Commun. 2023 Dec 14;14(1):8299. doi: 10.1038/s41467-023-43384-y.
PubMed 38097552Hanass-Hancock J, Carpenter B, Reddy T, Nzuza A, Gaffoor Z, Goga A, Andrasik M. Participants' characteristics and motivations to screen for HIV vaccine and monoclonal antibody trials in KwaZulu-Natal, South Africa. Trials. 2021 Dec 11;22(1):897. doi: 10.1186/s13063-021-05792-7.
PubMed 34895272