Evaluating the Safety and Efficacy of the VRC01 Antibody in Reducing Acquisition of HIV-1 Infection in Women
NCT ID: NCT02568215
Last Updated: 2022-02-23
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
1924 participants
INTERVENTIONAL
2016-05-31
2021-03-03
Brief Summary
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Detailed Description
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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
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Study Design
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RANDOMIZED
PARALLEL
PREVENTION
QUADRUPLE
Study Groups
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Group 1: Low-Dose VRC01
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.
VRC01
Administered by IV infusion; total dose will vary based on participant's weight
Group 2: High-Dose VRC01
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.
VRC01
Administered by IV infusion; total dose will vary based on participant's weight
Group 3: Placebo for VRC01
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.
Placebo for VRC01
Sodium Chloride for Injection USP, 0.9%; administered by IV infusion
Interventions
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VRC01
Administered by IV infusion; total dose will vary based on participant's weight
Placebo for VRC01
Sodium Chloride for Injection USP, 0.9%; administered by IV infusion
Other Intervention Names
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Eligibility Criteria
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Inclusion 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
* 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
Exclusion Criteria
* 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
* 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
18 Years
50 Years
FEMALE
Yes
Sponsors
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National Institute of Allergy and Infectious Diseases (NIAID)
NIH
Responsible Party
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Principal Investigators
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Lawrence Corey
Role: STUDY_CHAIR
HVTN; FHCRC
Myron Cohen
Role: STUDY_CHAIR
HPTN; University of North Carolina
Locations
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Gaborone CRS
Gaborone, South-East District, Botswana
Kisumu Crs
Kisumu, Nyanza, Kenya
Blantyre CRS
Blantyre, Southern Region, Malawi
Malawi CRS
Lilongwe, , Malawi
Polana Canico Health Research and Training Center (CISPOC), National Institute of Health (INS) CRS
Maputo, , Mozambique
The Aurum Institute Tembisa Clinical Research Centre CRS
Johannesburg, Gauteng, South Africa
Soweto HVTN CRS
Johannesburg, Gauteng, South Africa
Ward 21 CRS
Johannesburg, Gauteng, South Africa
Wits Reproductive Health and HIV Institute CRS (WRHI CRS)
Johannesburg, Gauteng, South Africa
Synexus Stanza Clinical Research Centre CRS
Pretoria, Gauteng, South Africa
Chatsworth CRS
Chatsworth, KwaZulu-Natal, South Africa
Botha's Hill CRS
Durban, KwaZulu-Natal, South Africa
CAPRISA eThekwini CRS
Durban, KwaZulu-Natal, South Africa
Vulindlela CRS
Durban, KwaZulu-Natal, South Africa
Aurum Institute Klerksdorp CRS
Klerksdorp, North West, South Africa
Rustenburg CRS
Rustenburg, North West, South Africa
Groote Schuur HIV CRS
Cape Town, Western Cape, South Africa
National Institute for Medical Research (NIMR) - Mbeya Medical Research Center (MMRC) Network CRS
Mbeya, , Tanzania
Seke South CRS
Chitungwiza, , Zimbabwe
Milton Park CRS
Harare, , Zimbabwe
Spilhaus CRS
Harare, , Zimbabwe
Countries
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References
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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.
Mgodi 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.
Huang 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.
Huang 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.
Corey 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.
Reeves 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.
Hanass-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.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Document Type: Informed Consent Form
Other Identifiers
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12045
Identifier Type: REGISTRY
Identifier Source: secondary_id
HVTN 703/HPTN 081
Identifier Type: -
Identifier Source: org_study_id
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