VRC-HIVMAB060-00-AB (VRC01) in People With Chronic HIV Infection Undergoing Analytical Treatment Interruption

NCT02471326 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 15014015-I-0140
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- A combination of daily drugs (called cART) can keep human immunodeficiency virus (HIV) very low for a long time. But cART can lose effectiveness and cause permanent side effects. If treatment stops, HIV levels go up again. Researchers want to see if a new product can control HIV levels when a person is off cART. Objective: \- To see if the new product VRC01 is safe and can control the HIV level in the blood when a person is not taking cART. Eligibility: \- Adults ages 18-65 with HIV who are willing to interrupt their treatment for at least 24 weeks. Design:

• Participants will be screened with:
• Physical exam
• Medical history
• Heart tests
• Blood and urine tests.
• Their HIV drugs may be switched. They will keep taking them until a few days after Visit 1.
• Visit 1: Repeat screening procedures.
• Participants will also have genetic testing and leukapheresis. For this, blood will be removed through a needle in one arm and circulated through a machine that removes white blood cells. The rest of the blood is returned through a needle in the other arm.
• They will get the first study drug dose through a thin tube in an arm vein for about 1 hour.
• For 24 weeks, participants will have 16 visits. They will have blood drawn every visit. At some visits they will repeat the screening procedures and get another VRC01 dose. They may have another leukapheresis.
• Four weeks after the last dose, participants will restart their cART. For 20 weeks, they will have monthly visits to repeat the screening procedures and discuss new symptoms.

Conditions

HIV

Keywords

HIV Neutralizing Antibodies; HIV Therapy

Outcome Measures

Primary Outcomes (1)

• Number of Grade 3 or Higher Adverse Events

  The primary endpoint was the number of grade 3 or higher adverse events, including serious adverse events, that were possibly related to VRC-HIVMAB060-00-AB (VRCO1).

  From the start of the initial infusion until up to 48 weeks.

Secondary Outcomes (1)

• Subjects Who Met Criteria to Restart Antiretroviral Therapy

  From Day 3 post initial infusion until up to 28 weeks.

Study Arms (1)

HIV Positive Subjects

EXPERIMENTAL

VRC-HIVMAB060-00-AB (VRC01) given in HIV-infected Adults (age 18-65 years) on cART with suppressed viremia

Biological: VRC-HIVMAB060-00-AB (VRC01)

Interventions

VRC-HIVMAB060-00-AB (VRC01) BIOLOGICAL

A potent HIV-specific monoclonal antibody

HIV Positive Subjects

Eligibility Criteria

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

You may qualify if:

• Age 18-65 years old.
• HIV-1 infection and clinically stable.
• In general good health and with an identified primary health care provider for medical management of HIV infection and willing to maintain a relationship with a primary health care provider for medical management of HIV infection while participating in the study.
• CD4+ cell count \>450 cells/mm\^3 at screening.
• Documentation of continuous cART treatment with suppression of plasma viral level below the limit of detection for greater than or equal to 3 years. Subjects with blips (i.e., detectable viral levels on cART) prior to screening may be included provided they satisfy the following criteria:
• The blips are \<400 copies/mL, and
• Succeeding viral levels return to levels below the limit of detection on subsequent testing.
• Willingness to undergo ATI.
• Laboratory values within pre-defined limits at screening:
• Absolute neutrophil count \>1,000/mm\^3.
• Hemoglobin levels \>10.0 g/dL for men and \>9.0 g/dL for women.
• Platelet count \>100,000/mm\^3.
• Prothrombin time (PT) and partial thromboplastin time (PTT) \<1.5 upper limit of normal (ULN).
• Estimated or a measured creatinine clearance rate of greater than or equal to 50 mL/min as determined by the NIH Clinical Center laboratory.
• AST and ALT levels of \<2.5 x ULN.

You may not qualify if:

• Chronic hepatitis B, as evidenced by a positive test for hepatitis B surface antigen (HBsAg), or chronic hepatitis C virus (HCV) infection, as evidenced by a positive test for HCV RNA. Subjects with a positive test for HCV antibody and a negative test for HCV RNA are eligible.
• Documented virologic failure to \>1 cART regimen.
• HIV immunotherapy or vaccine(s) received within 1 year prior to screening.
• Any licensed or experimental non-HIV vaccination (e.g., hepatitis B, influenza, pneumococcal polysaccharide) received within 2 weeks prior to study enrollment.
• Receipt of other investigational study agent within 28 days of enrollment.
• Any active malignancy that may require systemic chemotherapy or radiation therapy.
• Systemic immunosuppressive medications received within 3 months prior to enrollment (Not excluded: corticosteroid nasal spray or inhaler; topical corticosteroids for mild, uncomplicated dermatitis; or oral/parenteral corticosteroids administered for non-chronic conditions not expected to recur \[length of therapy less than or equal to 10 days, with completion in greater than or equal to 30 days prior to enrollment\]).
• History or other clinical evidence of:
• Significant or unstable cardiac disease (e.g., angina, congestive heart failure, recent myocardial infarction).
• Severe illness, malignancy, immunodeficiency other than HIV, or any other condition that, in the opinion of the investigator, would make the subject unsuitable for the study.
• Active drug or alcohol use or any other pattern of behavior that, in the opinion of the investigator, would interfere with adherence to study requirements.
• Breast-feeding.

Sponsors & Collaborators

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

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• 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

• Shingai M, Nishimura Y, Klein F, Mouquet H, Donau OK, Plishka R, Buckler-White A, Seaman M, Piatak M Jr, Lifson JD, Dimitrov DS, Nussenzweig MC, Martin MA. Antibody-mediated immunotherapy of macaques chronically infected with SHIV suppresses viraemia. Nature. 2013 Nov 14;503(7475):277-80. doi: 10.1038/nature12746. Epub 2013 Oct 30.

  PMID: 24172896 BACKGROUND

• Chun TW, Murray D, Justement JS, Blazkova J, Hallahan CW, Fankuchen O, Gittens K, Benko E, Kovacs C, Moir S, Fauci AS. Broadly neutralizing antibodies suppress HIV in the persistent viral reservoir. Proc Natl Acad Sci U S A. 2014 Sep 9;111(36):13151-6. doi: 10.1073/pnas.1414148111. Epub 2014 Aug 25.

  PMID: 25157148 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 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Interventions

VRC01 monoclonal antibody

Results Point of Contact

• Title: Sneller, Michael
• Organization: National Institute of Allergy and Infectious Diseases

MSNELLER@niaid.nih.gov

+1 301 496 0491

Study Officials

• Michael C Sneller, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: June 12, 2015
• First Posted: June 15, 2015
• Study Start: July 13, 2015
• Primary Completion: April 7, 2017
• Study Completion: April 7, 2017
• Last Updated: October 31, 2017
• Results First Posted: October 31, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will share

Locations

US (1)