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

• ClinicalTrials.gov Identifier: NCT02664415
• Recruitment Status: Completed
• First Posted: January 27, 2016
• Results First Posted: October 17, 2018
• Last Update Posted: November 2, 2021
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)

Study Description

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.

Condition or disease	Intervention/treatment	Phase
HIV Infections	Biological: VRC01; Biological: Placebo for VRC01	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 23 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: August 2016
• Actual Primary Completion Date: August 4, 2017
• Actual Study Completion Date: August 4, 2017

Arms and Interventions

Arm	Intervention/treatment
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.	Biological: VRC01; 40 mg/kg; administered IV; Other Name: VRC-HIVMAB060-00-AB
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.	Biological: Placebo for VRC01; Sodium Chloride for Injection 0.9%, USP; administered IV

Outcome Measures

Primary Outcome Measures :

1. 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
2. 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.

Secondary Outcome Measures :

1. 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
2. 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.
3. 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.
4. 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.
5. 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.
6. 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
7. 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
8. 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.
9. 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.
10. 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.

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 50 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Thailand

SEARCH Thai Red Cross AIDS Research Centre Non-Network CRS

Bangkok, Thailand, 10330

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Study Chair: Trevor Crowell, MD, PhD; US Military HIV Research Program

  Study Documents (Full-Text)

Documents provided by National Institute of Allergy and Infectious Diseases (NIAID):

Study Protocol  [PDF] December 1, 2016

Statistical Analysis Plan  [PDF] December 1, 2016

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT02664415
• Obsolete Identifiers: NCT03036709
• Other Study ID Numbers: RV 397; 12001 ( Registry Identifier: DAIDS-ES Registry Number )
• First Posted: January 27, 2016
• Results First Posted: October 17, 2018
• Last Update Posted: November 2, 2021
• Last Verified: October 2021

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Human Monoclonal Antibody

Additional relevant MeSH terms:

Infections; Communicable Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Disease Attributes; Pathologic Processes; Blood-Borne Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases