Evaluating the Safety, Pharmacokinetics, and Antiviral Activity of a Human Monoclonal Antibody (VRC01) in HIV-Infected Adults Undergoing a Brief Treatment Interruption

NCT02463227 | Completed Phase 1 Results DMC

• 2 other identifiers: A534011998
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study was to evaluate the safety, tolerability, pharmacokinetics (PK), and antiviral activity of an antibody (called VRC01) in HIV-infected adults whose HIV was well-controlled with HIV medicines. The study examined whether VRC01 controlled or delayed the return of HIV viremia when the participants' HIV medicines were briefly stopped during the study.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants Who Experienced a Grade 3 or Higher Systemic (i.e., Not a Local Reaction) Adverse Event (AE) That is Possibly, Probably, or Definitely Related to the Administration of the VRC01 Antibody

  The primary safety outcome examined the occurrence of a Grade 3 or higher systemic (i.e., not a local reaction) adverse event (AE) possibly, probably, or definitely related to the administration of the VRC01 antibody. The DAIDS AE Grading Table (V2.0) was used.

  Measured from entry through week 21 (Steps 1 and 2)

• Percentage of Participants Who Had a Confirmed HIV-1 RNA Greater Than or Equal to 200 Copies/mL at Week 8 of the Analytical Treatment Interruption (ATI) or Indication to Re-initiate ART Prior to Week 8 of the ATI

  The primary efficacy outcome is the percentage of participants who had a confirmed HIV-1 RNA greater than or equal to 200 copies/mL at week 8 of the analytical treatment interruption (ATI) or indication to re-initiate ART prior to week 8 of the ATI.

  Measured at Weeks 1, 2, 3, 4, 5, 6, 7, and 8 of the ATI

Secondary Outcomes (3)

• Measured Value of Plasma VRC01 at the Time of Rebound

  Measured from entry through week 21 (Steps 1 and 2)

• Measured Values of VRC01 in Plasma in the First 8 Weeks of the Analytical Treatment Interruption (ATI)

  Measured at weeks 1, 2, 3, 4, 5, 6, 7, and 8 of the ATI

• Percentage of Participants Who Had a Confirmed HIV-1 RNA Greater Than or Equal to 200 Copies/mL at Week 4 of the ATI or Indication to Reinitiate ART Prior to Week 4 of the ATI

  Measured at weeks 1, 2, 3, and 4 of the ATI

Study Arms (1)

VRC01

EXPERIMENTAL

Participants received an IV infusion of 40 mg/kg of VRC01 on study days 0, 21, and 42.

Biological: VRC01

Interventions

VRC01 BIOLOGICAL

40 mg/kg of VRC01 administered IV in 100 mL of 0.9% sodium chloride for injection, USP. Administered over about 30 to 60 minutes using a volumetric pump.

Also known as: VRC-HIVMAB060-00-AB

VRC01

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load (VL). More information on this criterion can be found in the protocol.
• Ability and willingness of participant or legal representative to provide informed consent
• Clinically stable on their first or second ART regimen that includes a boosted protease inhibitor or an integrase inhibitor. The current regimen should have been stable for 8 weeks at the time of entry. Changes while the patient HIV viral load was undetectable did not count toward the number of ART regimens used, (for example, an individual switching from a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen to an integrase inhibitor based regimen while the HIV viral load is undetectable would still be on their first regimen).
• HIV-1 RNA that is less than 50 copies/mL using a Food and Drug Administration (FDA)-approved assay performed by any laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent within 45 days prior to study entry
• HIV-1 RNA less than 50 copies/mL using a FDA-approved assay for at least 24 weeks prior to study entry performed by any laboratory that had a CLIA certification or its equivalent. More information on this criterion can be found in the protocol.
• Screening CD4+ T-cell count greater than or equal to 450 cells/μL within 45 days prior to study entry
• Nadir CD4+ T-cell count greater than 200 cells/μL
• Willingness to have blood samples collected, stored indefinitely, and used for study-related research purposes
• The following laboratory values obtained within 45 days prior to enrollment:
• Absolute neutrophil count (ANC) greater than or equal to 1000 cells/mm\^3
• Hemoglobin greater than or equal to 12.0 g/dL for men and greater than or equal to 11.0 g/dL for women
• Platelet count greater than or equal to 100,000/mm\^3
• Creatinine clearance greater than or equal to 60 mL/min estimated by the Cockcroft-Gault equation. More information on this criterion can be found in the protocol.
• Alanine aminotransferase (ALT) less than or equal to 2.0 times the upper limit of normal (ULN)
• At least eight participants had availability of plasma or serum specimen before the initiation of ART either in the Center for AIDS Research (CFAR) repository of the University of Pennsylvania, University of Alabama, or in the AIDS Clinical Trials Group (ACTG) central repository

You may not qualify if:

• Previous receipt of humanized or human monoclonal antibody whether licensed or investigational
• Weight greater than 115 kg or less than 53 kg
• History of an AIDS-defining illness
• Ongoing AIDS-related opportunistic infection (including oral thrush)
• History of a severe allergic reaction with generalized urticaria, angioedema, or anaphylaxis in the 2 years prior to enrollment
• Currently breastfeeding
• Receipt of other investigational study agent within 30 days prior to enrollment
• Treatment with systemic glucocorticoids (e.g., prednisone or other glucocorticoid) or other immunomodulators (other than nonsteroidal anti-inflammatory drugs \[NSAIDs\]) within 30 days prior to enrollment
• Any other chronic or clinically significant medical condition that in the opinion of investigator would have jeopardized the safety or rights of the participant, including, but not limited to diabetes mellitus type I, OR clinically significant forms of drug or alcohol abuse, severe asthma, autoimmune disease, uncontrolled hypertension, liver disease, psychiatric disorders, heart disease, or cancer
• Treatment during acute infection (i.e., treatment within 6 months of acute infection)
• Current use of a NNRTI
• Non-participation in Step 1
• Non-participation in Step 2

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (2)

Alabama CRS

Birmingham, Alabama, 35294, United States

Location

Penn Therapeutics, CRS

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (7)

• Zhou T, Georgiev I, Wu X, Yang ZY, Dai K, Finzi A, Kwon YD, Scheid JF, Shi W, Xu L, Yang Y, Zhu J, Nussenzweig MC, Sodroski J, Shapiro L, Nabel GJ, Mascola JR, Kwong PD. Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. Science. 2010 Aug 13;329(5993):811-7. doi: 10.1126/science.1192819. Epub 2010 Jul 8.

  PMID: 20616231 BACKGROUND

• Li Y, O'Dell S, Walker LM, Wu X, Guenaga J, Feng Y, Schmidt SD, McKee K, Louder MK, Ledgerwood JE, Graham BS, Haynes BF, Burton DR, Wyatt RT, Mascola JR. Mechanism of neutralization by the broadly neutralizing HIV-1 monoclonal antibody VRC01. J Virol. 2011 Sep;85(17):8954-67. doi: 10.1128/JVI.00754-11. Epub 2011 Jun 29.

  PMID: 21715490 BACKGROUND

• U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS. Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0. [November 2014]. Available from: http://rsc.tech-res.com/docs/default-source/safety/daids_ae_grading_table_v2_nov2014.pdf

  BACKGROUND

• Manual for Expedited Reporting of Adverse Events to DAIDS, Version 2.0, January 2010.

  BACKGROUND

• Bar KJ, Sneller MC, Harrison LJ, Justement JS, Overton ET, Petrone ME, Salantes DB, Seamon CA, Scheinfeld B, Kwan RW, Learn GH, Proschan MA, Kreider EF, Blazkova J, Bardsley M, Refsland EW, Messer M, Clarridge KE, Tustin NB, Madden PJ, Oden K, O'Dell SJ, Jarocki B, Shiakolas AR, Tressler RL, Doria-Rose NA, Bailer RT, Ledgerwood JE, Capparelli EV, Lynch RM, Graham BS, Moir S, Koup RA, Mascola JR, Hoxie JA, Fauci AS, Tebas P, Chun TW. Effect of HIV Antibody VRC01 on Viral Rebound after Treatment Interruption. N Engl J Med. 2016 Nov 24;375(21):2037-2050. doi: 10.1056/NEJMoa1608243. Epub 2016 Nov 9.

  PMID: 27959728 RESULT

• Weir IR, Harrison LJ. An evaluation of confidence intervals for a cumulative proportion to enable decisions at interim reviews of single-arm trials. Contemp Clin Trials. 2024 Mar;138:107453. doi: 10.1016/j.cct.2024.107453. Epub 2024 Jan 20.

  PMID: 38253253 DERIVED

• Salantes DB, Zheng Y, Mampe F, Srivastava T, Beg S, Lai J, Li JZ, Tressler RL, Koup RA, Hoxie J, Abdel-Mohsen M, Sherrill-Mix S, McCormick K, Overton ET, Bushman FD, Learn GH, Siliciano RF, Siliciano JM, Tebas P, Bar KJ. HIV-1 latent reservoir size and diversity are stable following brief treatment interruption. J Clin Invest. 2018 Jul 2;128(7):3102-3115. doi: 10.1172/JCI120194. Epub 2018 Jun 18.

  PMID: 29911997 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

VRC01 monoclonal antibody

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; 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

Results Point of Contact

• Title: ACTG Clinicaltrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.

ACTGCT.Gov@s3.com

(301) 628-3313

Study Officials

• Pablo Tebas, MD

  University of Pennsylvania

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2015
• First Posted: June 4, 2015
• Study Start: August 1, 2015
• Primary Completion: March 1, 2016
• Study Completion: October 1, 2016
• Last Updated: October 19, 2021
• Results First Posted: April 20, 2017

Record last verified: 2017-03

Locations

US (2)