Clinical trial NCT02568215: Evaluating the Safety and Efficacy of the VRC01 Antibody in Reducing Acquisition of HIV-1 Infection in Women
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: HIV-1 Infections
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2015-10-05
Enrollment: 1924
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

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
* 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:

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

* 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

Primary outcomes:
measure: Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Pain and/or Tenderness
timeFrame: Measured through 3 days after each infusion at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, 72.
measure: Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Erythema and/or Induration
timeFrame: Measured through 3 days after each infusion at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, 72.
measure: Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms
timeFrame: Measured through 3 days after each infusion at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, 72.
measure: Chemistry and Hematology Laboratory Measures - Alanine Aminotransferase (ALT)
timeFrame: Measured at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, 72.
measure: Chemistry and Hematology Laboratory Measures - Creatinine
timeFrame: Measured at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, 72.
measure: Chemistry and Hematology Laboratory Measures - Hemoglobin
timeFrame: Measured at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, 72.
measure: Chemistry and Hematology Laboratory Measures - Lymphocyte Count, Neutrophil Count
timeFrame: Measured at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, 72.
measure: Chemistry and Hematology Laboratory Measures - Platelets, White Blood Cells (WBC)
timeFrame: Measured at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, 72.
measure: Chemistry and Hematology Laboratory Measures Meeting Grade 3 AE Criteria or Above
timeFrame: Measured at Weeks 8, 16, 24, 32, 40, 48, 56, 64, 72.
measure: Number of Participants With Early Infusion Discontinuation and Reasons for Discontinuation
timeFrame: Measured through Week 72 (the last infusion visit).
measure: Incidence Rate of Early Infusion Discontinuation
timeFrame: Measured through Week 72 (the last infusion visit).
measure: Number of Participants With Documented HIV-1 Infection by the Week 80 Visit
timeFrame: Measured through Week 80.
Secondary outcomes:
measure: Serum Concentration of VRC01 in Participants Assigned to Receive the mAb
timeFrame: 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.
measure: VRC01 Clinical Lot Neutralization of Founder Viruses (IC80)
timeFrame: Measured through Week 80.
measure: VRC01 Serum Neutralization of Autologous Founder Viruses (ID50, ID80)
timeFrame: First RNA+ Sample detected from baseline up to Week 104.
Other outcomes:
Locations:
city: Gaborone
country: Botswana
facility: Gaborone CRS
state: South-East District
city: Kisumu
country: Kenya
facility: Kisumu Crs
state: Nyanza
city: Blantyre
country: Malawi
facility: Blantyre CRS
state: Southern Region
city: Lilongwe
country: Malawi
facility: Malawi CRS
city: Maputo
country: Mozambique
facility: Polana Canico Health Research and Training Center (CISPOC), National Institute of Health (INS) CRS
city: Johannesburg
country: South Africa
facility: The Aurum Institute Tembisa Clinical Research Centre CRS
state: Gauteng
city: Johannesburg
country: South Africa
facility: Soweto HVTN CRS
state: Gauteng
city: Johannesburg
country: South Africa
facility: Ward 21 CRS
state: Gauteng
city: Johannesburg
country: South Africa
facility: Wits Reproductive Health and HIV Institute CRS (WRHI CRS)
state: Gauteng
city: Pretoria
country: South Africa
facility: Synexus Stanza Clinical Research Centre CRS
state: Gauteng
city: Durban
country: South Africa
facility: Botha's Hill CRS
state: Kwa Zulu Natal
city: Chatsworth
country: South Africa
facility: Chatsworth CRS
state: KwaZulu-Natal
city: Durban
country: South Africa
facility: CAPRISA eThekwini CRS
state: KwaZulu-Natal
city: Durban
country: South Africa
facility: Vulindlela CRS
state: KwaZulu-Natal
city: Klerksdorp
country: South Africa
facility: Aurum Institute Klerksdorp CRS
state: North West Province
city: Rustenburg
country: South Africa
facility: Rustenburg CRS
state: North West Province
city: Cape Town
country: South Africa
facility: Groote Schuur HIV CRS
state: Western Cape Province
city: Mbeya
country: Tanzania
facility: National Institute for Medical Research (NIMR) - Mbeya Medical Research Center (MMRC) Network CRS
city: Chitungwiza
country: Zimbabwe
facility: Seke South CRS
city: Harare
country: Zimbabwe
facility: Milton Park CRS
city: Harare
country: Zimbabwe
facility: Spilhaus CRS
Study officials:
affiliation: HVTN; FHCRC
name: Lawrence Corey
role: STUDY_CHAIR
affiliation: HPTN; University of North Carolina
name: Myron Cohen
role: STUDY_CHAIR
References:
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citation: 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.
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