Combination Therapy With VRC01 and 10-1074 in HIV-Infected Individuals Undergoing Sequential Treatment Interruptions

NCT03831945 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 19004819-I-0048
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

Background: A daily drug combination can keep human immunodeficiency virus (HIV) levels low for a long time. But if this combination antiretroviral therapy (ART) stops, HIV levels go back up. People can also develop resistance or permanent side effects. Researchers want to see if 2 new drugs can help control HIV when a person is not on ART. Objective: To see if VRC01 and 10-1074 are safe and control HIV when a person is not on ART. Eligibility: Adults 18-65 with HIV Design: All participants must agree to practice safer sex. Those who can get pregnant will have a pregnancy test every visit. Participants will be screened with: Physical exam Medicine review Blood and urine tests Some participants may need to change their HIV medicine for a brief period of time during the study. A few weeks later, participants will repeat screening tests and stop taking their HIV medicines. Interruption phase 1: Participants will have blood tests every 2 weeks, and repeat screening tests every 4 weeks. Treatment phase: Once their HIV reaches a certain level in the blood, participants will get the 2 study drugs or a salt water placebo. They will not know which they get. Each substance will be given through a thin tube in an arm vein for about 1 hour. Participants will restart their HIV medicines and repeat screening tests every 4 weeks. Interruption phase 2: Once the level of HIV in the blood becomes undetectable for 3 months, participants will again stop taking their HIV medicines and have blood tests every 2 weeks to monitor the level of HIV in the blood. Participants will restart their medicines by week 24. They will start sooner if they have certain symptoms or blood levels of HIV become too high. They will repeat most screening tests 3 times over 24 weeks.

Conditions

HIV

Keywords

HIV Therapy; HIV Neutralizing Antibodies

Outcome Measures

Primary Outcomes (1)

• Days From Start of the Second Treatment Interruption Until the Subject Meets Criteria to Restart ART

  Number of days from start of the second analytical treatment interruption (ATI) until the subject meets criteria to restart Antiretroviral Therapy (ART) before Week 16 \[a confirmed \>30% decline in baseline CD4+ T Cell count or an absolute CD4+ T Cell count in the setting of detectable HIV viremia (\>40 copies/mL); a sustained (\>4weeks) HIV RNA level of \> 1000 copies/mL, or any HIV related symptoms or pregnancy.\]

  From start of second Analytical Treatment Interruption (ATI) until up to 16 weeks

Secondary Outcomes (1)

• Percent of Participants With Grade 3 or Higher Related Adverse Events

  From the start of the initial infusion through follow-up phase week 24

Study Arms (2)

Single infusion of VRC01 and 10-1074

ACTIVE COMPARATOR

Single infusion of 40 mg/kg VRC-HIVMAB060-00-AB (VRC01) in 100 mL of saline and 30 mg/kg of 10-1074 in 250 mL of saline when viral load is \>/= 200 copies/mL in HIV-infected individuals undergoing antiretroviral treatment interruption.

Biological: VRC-HIVMAB060-00-AB (VRC01); Biological: 10-1074

Single infusion of Normal Saline

PLACEBO COMPARATOR

Single infusion of 100 mL and 250 mL of normal saline when viral load is \>/= 200 copies/mL in HIV-infected individuals undergoing antiretroviral treatment interruption.

Biological: Normal Saline Placebo

Interventions

VRC-HIVMAB060-00-AB (VRC01) BIOLOGICAL

VRC01 is a broadly neutralizing human mAb targeted against the HIV-1CD4 binding site. As single intravenous infusion of VRC01(40 mg/kg) plus10-1074 (30mg/kg) or placebo will be administered after the first analytical treatment interruption phase once the subject's plasma viremia is \> or = 200 copies/mL.

Single infusion of VRC01 and 10-1074

10-1074 BIOLOGICAL

10-1074 is a recombinant, fully human mAb of the IgG1 lambda isotype that specifically binds to the base of the V3 loop within HIV-1 envelope gp-120. A single intravenous infusion of VRC01 (40 mg/kg) plus 10-1074 (30 mg/kg) or placebo will be administered after the first analytical treatment interruption phase once the subject's plasma viremia is \> or = 200 copies/mL.

Single infusion of VRC01 and 10-1074

Normal Saline Placebo BIOLOGICAL

2 sequential infusions of normal saline placebo in matching volumes to antibody infusions will be administered after the first analytical treatment interruption phase once the subject's plasma viremia is \> or = 200 copies/mL.

Single infusion of Normal Saline

Eligibility Criteria

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

You may qualify if:

• years of age.
• HIV-1 infection and clinically stable.
• General good health and has an identified primary health care provider for medical management of HIV infection and is willing to maintain a relationship with a primary health care provider for medical management of HIV infection while participating in the study.
• CD4+ T cell count \>450 cells/mm(3) at screening.
• Documentation of continuous ART treatment with suppression of plasma viral level below the lower limit of quantification (LLOQ) for the assay used for greater than or equal to 2 years. Individuals with blips (i.e., detectable viral levels on ART) 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.
• 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).
• Estimated or a measured glomerular filtration rate \>60 mL/min/1.73 m(2) as determined by the NIH Clinical Center (CC) laboratory.
• Aspartate aminotransferase (AST) and alanine transaminase (ALT) levels of \<2.5 times upper limit of normal (ULN), direct bilirubin within the normal range for the NIH CC laboratory.
• Willingness to have samples stored for future research.
• Willingness to undergo analytical treatment interruption (ATI)

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.
• HIV immunotherapy or HIV vaccine(s) received within 1 year prior to screening.
• Any prior history of receiving 10-1074 or VRC01.
• 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 (Exceptions: \[1\] corticosteroid nasal spray or inhaler; \[2\] topical corticosteroids for mild, uncomplicated dermatitis; or \[3\] 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 or cerebrovascular disease (e.g., angina, congestive heart failure, recent stroke or 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.
• Pregnancy or breast-feeding at time of screening.
• Documented multiclass antiretroviral drug resistance that, in the judgment of the investigator, would pose a risk of virologic failure should additional mutations develop during the study.

Sponsors & Collaborators

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

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Nishimura Y, Gautam R, Chun TW, Sadjadpour R, Foulds KE, Shingai M, Klein F, Gazumyan A, Golijanin J, Donaldson M, Donau OK, Plishka RJ, Buckler-White A, Seaman MS, Lifson JD, Koup RA, Fauci AS, Nussenzweig MC, Martin MA. Early antibody therapy can induce long-lasting immunity to SHIV. Nature. 2017 Mar 23;543(7646):559-563. doi: 10.1038/nature21435. Epub 2017 Mar 13.

  PMID: 28289286 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 BACKGROUND

• Mendoza P, Gruell H, Nogueira L, Pai JA, Butler AL, Millard K, Lehmann C, Suarez I, Oliveira TY, Lorenzi JCC, Cohen YZ, Wyen C, Kummerle T, Karagounis T, Lu CL, Handl L, Unson-O'Brien C, Patel R, Ruping C, Schlotz M, Witmer-Pack M, Shimeliovich I, Kremer G, Thomas E, Seaton KE, Horowitz J, West AP Jr, Bjorkman PJ, Tomaras GD, Gulick RM, Pfeifer N, Fatkenheuer G, Seaman MS, Klein F, Caskey M, Nussenzweig MC. Combination therapy with anti-HIV-1 antibodies maintains viral suppression. Nature. 2018 Sep;561(7724):479-484. doi: 10.1038/s41586-018-0531-2. Epub 2018 Sep 26.

  PMID: 30258136 BACKGROUND

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: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2019
• First Posted: February 6, 2019
• Study Start: April 4, 2019
• Primary Completion: December 8, 2020
• Study Completion: December 8, 2020
• Last Updated: October 12, 2021
• Results First Posted: October 12, 2021

Record last verified: 2021-08

Locations

US (1)