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Safety and Therapeutic Efficacy of the VRC01 Antibody in Patients Who Initiated Antiretroviral Therapy During Early Acute HIV Infection

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ClinicalTrials.gov Identifier: NCT02664415
Recruitment Status : Completed
First Posted : January 27, 2016
Results First Posted : October 17, 2018
Last Update Posted : October 17, 2018
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information
First Submitted Date  ICMJE January 20, 2016
First Posted Date  ICMJE January 27, 2016
Results First Submitted Date  ICMJE August 3, 2018
Results First Posted Date  ICMJE October 17, 2018
Last Update Posted Date October 17, 2018
Study Start Date  ICMJE August 2016
Actual Primary Completion Date August 4, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 16, 2018)
  • Number of Participants With Serious Adverse Event [ Time Frame: Measured up to 10 weeks after last infusion of VRC01 or placebo ]
    Participants were monitored for up to 10 weeks after the last infusion of VRC01 or placebo
  • Number of Participants With Sustained Virologic Suppression [ Time Frame: Measured through 24 weeks after ATI ]
    Number of participants who sustained virologic control (HIV RNA <50 copies/mL), without indication for ART resumption at week 24.
Original Primary Outcome Measures  ICMJE
 (submitted: January 22, 2016)
  • Incidence of serious adverse event at any time up to 10 weeks after the last infusion of VRC01 or placebo [ Time Frame: Measured through Week 34 ]
  • Number of participants with sustained virologic suppression, without indication for ART resumption [ Time Frame: Measured through Week 24 ]
    sustained virologic control (HIV RNA <50 copies/mL)
Change History Complete list of historical versions of study NCT02664415 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 16, 2018)
  • Time to Viral Rebound After Cessation of ART [ Time Frame: Measured from Baseline ATI through ART resumption. ]
    This is the days from Analytic Treatment Interruption (ATI) to:
    1. HIV RNA >= 20 copies/mL.
    2. HIV RNA >= 1000 copies/mL
  • Level of Rebound Viremia After Cessation of ART [ Time Frame: Measured from Baseline ATI through ART resumption. ]
    This is the HIV-1 RNA levels (copies/mL) at first detection and ART resumption.
  • Time to ART Resumption for Any Reason After Cessation of ART [ Time Frame: Measured from Baseline ATI through ART resumption. ]
    This is the days from ATI to ART resumptions.
  • Number of Participants With Detectable HIV-1 RNA Via Single Copy Assay [ Time Frame: Measured from Baseline ATI through ART resumption. ]
    This is number of participants who had detectable HIV-1 RNA via the ultrasensitive single copy assay prior to detectability on the routine assay.
  • Change in CD4+ T Cell Count From ATI to ART Resumption [ Time Frame: Measured from Baseline ATI through ART resumption ]
    This is change in CD4+ T cell count from ATI to ART resumption.
  • Total HIV DNA in the Peripheral Compartment [ Time Frame: Measured from ATI through 6 months after ART resumption ]
    This is total HIV DNA levels at baseline ATI, ART resumption and 6 month after ART resumption
  • Number of Participants Hospitalized. [ Time Frame: Measured up to 10 weeks after the last infusion of VRC01 or placebo ]
    Participants were monitored for up to 10 weeks after the last infusion of VRC01 or placebo
  • Number of Participants With Acute Retroviral Syndrome (ARS) [ Time Frame: Measured from Baseline ATI through ART resumption. ]
    This is the number of participants who have developed during ATI.
  • Neuropsychological Battery Performance [ Time Frame: Measured from Baseline ATI through ART resumption. ]
    This is a NPZ-4 score,a 4-test NP battery evaluated fine motor function/manual dexterity [Grooved Pegboard test (GP), non-dominant hand], psychomotor speed [Color Trails 1 (CT1), Trail Making A (TM)], and executive function/set shifting [Color Trails 2 (CT2)]. Individual test raw scores were converted to z-scores. Z-scores range from -3 standard deviations up to +3 standard deviations. Higher scores indicate better test performance and lower cognitive impairment.
  • Computed Score on the Control and Attention Task (i.e., Flanker Task) [ Time Frame: Measured from Baseline ATI through ART resumption. ]
    The Flanker is a measure of executive function, specifically tapping inhibitory control and attention.The scores range from 0 to 10. A higher scores indicate higher levels of ability to attend to relevant stimuli and inhibit attention from irrelevant stimuli.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 22, 2016)
  • Time to Viral Rebound After Cessation of ART [ Time Frame: Measured through Week 48 ]
  • Level of Rebound Viremia After Cessation of ART [ Time Frame: Measured through Week 48 ]
  • Time to ART Resumption for Any Reason After Cessation of ART [ Time Frame: Measured through Week 48 ]
  • Detectable HIV RNA via single copy assay [ Time Frame: Measured through Week 48 ]
  • CD4+ T cell count [ Time Frame: Measured through Week 48 ]
  • Cell-associated HIV RNA and DNA in the peripheral compartment [ Time Frame: Measured through Week 48 ]
  • Neuropsychological battery performance [ Time Frame: Measured through Week 48 ]
  • Score on the Control and Attention task (i.e., Flanker Task) (computerized test of cognition) [ Time Frame: Measured through Week 48 ]
  • Frequency of hospitalization [ Time Frame: Measured through Week 48 ]
  • Incidence of non-AIDS related conditions [ Time Frame: Measured through Week 48 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Therapeutic Efficacy of the VRC01 Antibody in Patients Who Initiated Antiretroviral Therapy During Early Acute HIV Infection
Official Title  ICMJE Safety and Therapeutic Efficacy of the Broadly Neutralizing HIV-1 Specific Monoclonal Antibody VRC01 During Analytic Treatment Interruption in Patients Who Initiated Antiretroviral Therapy During Early Acute HIV Infection
Brief Summary The study will evaluate the safety and therapeutic efficacy of the human monoclonal antibody (mAb) VRC-HIVMAB060-00-AB (VRC01), when administered during analytic treatment interruption (ATI), in adults who began antiretroviral therapy (ART) during early acute HIV infection.
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 therapeutic efficacy of VRC01, when administered during analytic treatment interruption (ATI), in adults who began antiretroviral therapy (ART) during early acute HIV infection.

The study will enroll participants from the RV 254 study who were diagnosed during early acute HIV infection and who have been on ART. At study entry, participants will stop taking their antiretroviral (ARV) medications. They will be randomly assigned to receive an intravenous (IV) infusion of VRC01 or placebo at Weeks 0 (study entry), 3, 6, 9, 12, 15, 18, 21, and 24. For 7 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 follow-up visits for 48 weeks. Study visits may include physical examinations, blood collection, and urine collection. Neurocognitive testing will take place at select study visits. Some participants may take part in optional study procedures including mucosal secretion collection, MRI brain scan, colon biopsy, lymph node biopsy, leukapheresis, and lumbar puncture.

Study staff will monitor participants' HIV throughout the study, and participants will end their participation in the study and restart their ARV medications, if needed.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE HIV Infections
Intervention  ICMJE
  • Biological: VRC01
    40 mg/kg; administered IV
    Other Name: VRC-HIVMAB060-00-AB
  • Biological: Placebo for VRC01
    Sodium Chloride for Injection 0.9%, USP; administered IV
Study Arms  ICMJE
  • Experimental: VRC01
    Participants will receive an intravenous (IV) infusion of 40 mg/kg of VRC01 at Week 0 and every 3 weeks until Week 24 or until criteria for resumption of ART are met.
    Intervention: Biological: VRC01
  • Placebo Comparator: Placebo for VRC01
    Participants will receive an IV infusion of placebo at Week 0 and every 3 weeks until Week 24 or until criteria for resumption of ART are met.
    Intervention: Biological: Placebo for VRC01
Publications * Crowell TA, Colby DJ, Pinyakorn S, Sacdalan C, Pagliuzza A, Intasan J, Benjapornpong K, Tangnaree K, Chomchey N, Kroon E, de Souza MS, Tovanabutra S, Rolland M, Eller MA, Paquin-Proulx D, Bolton DL, Tokarev A, Thomas R, Takata H, Trautmann L, Krebs SJ, Modjarrad K, McDermott AB, Bailer RT, Doria-Rose N, Patel B, Gorelick RJ, Fullmer BA, Schuetz A, Grandin PV, O'Connell RJ, Ledgerwood JE, Graham BS, Tressler R, Mascola JR, Chomont N, Michael NL, Robb ML, Phanuphak N, Ananworanich J; RV397 Study Group. Safety and efficacy of VRC01 broadly neutralising antibodies in adults with acutely treated HIV (RV397): a phase 2, randomised, double-blind, placebo-controlled trial. Lancet HIV. 2019 May;6(5):e297-e306. doi: 10.1016/S2352-3018(19)30053-0. Epub 2019 Apr 15.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 16, 2018)
23
Original Estimated Enrollment  ICMJE
 (submitted: January 22, 2016)
24
Actual Study Completion Date  ICMJE August 4, 2017
Actual Primary Completion Date August 4, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Able and willing to provide written informed consent or, in the case of illiteracy, witnessed verbal informed consent with documentation of a thumbprint in lieu of a signature.
  • Passes Test of Understanding.
  • Man or woman aged 20-50 years.
  • Initiated on ART during acute HIV infection (Fiebig Stage I to III at RV 254 enrollment).
  • Prescribed ART for at least 24 months prior to enrollment.
  • HIV-1 RNA less than 50 copies/mL on at least three consecutive measurements within the past 12 months.
  • Integrated HIV DNA in peripheral blood mononuclear cells (PBMCs) below the level of detection (1 copy/10^5 PBMCs) within 6 months prior to enrollment.
  • Last documented peripheral blood CD4 greater than 400 cells/mm^3 within 3 months prior to enrollment.
  • No HIV-related or AIDS-defining illness within 6 months prior to enrollment.
  • In general good health.
  • Able to participate in study visits.

Female-Specific Criteria:

  • Agrees not to become pregnant from the time of study enrollment until the last study visit. If a woman is sexually active and has no history of hysterectomy or tubal ligation or menopause, she must agree to use a prescription birth control method or a barrier birth control method.
  • Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test (urine or serum) on day of enrollment for any women unless she is post-menopause for 24 consecutive months or has undergone a surgical procedure that precludes pregnancy.

Exclusion Criteria:

  • Previous receipt of humanized or human monoclonal antibody whether licensed or investigational.
  • Ongoing AIDS-related opportunistic infection (including oral thrush).
  • 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 requiring daily treatment.
  • Physical finding on examination considered indicative of significant disease such as murmur (other than functional), hepatosplenomegaly, or focal neurologic deficit.
  • Hypertension that is not well controlled by medication.
  • Hepatitis B surface antigen positive at any time in the past.
  • Hepatitis C antibody positive at any time in the past.
  • Untreated syphilis.
  • Estimated glomerular filtration rate (GFR) less than 50 ml/min within the past 90 days.
  • Pregnant or breastfeeding.
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Thailand
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02664415
Other Study ID Numbers  ICMJE RV 397
12001 ( Registry Identifier: DAIDS-ES Registry Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institute of Allergy and Infectious Diseases (NIAID)
Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Jintanat Ananworanich, MD, PhD US Military HIV Research Program
PRS Account National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP