Clinical Trials

MainTitle

Long-Acting Cabotegravir Plus VRC01LS for Viral Suppression in Adults Living With HIV-1

This study is not yet open for participant recruitment. (see Contacts and Locations)

Verified July 2019 by National Institute of Allergy and Infectious Diseases (NIAID)

Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator
ViiV

Information provided by (Responsible Party)
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier
NCT03739996

First received: November 9, 2018
Last updated: July 22, 2019
Last Verified: July 2019
History of Changes
Purpose

Purpose

The purpose of this study is to assess the safety, tolerability, pharmacokinetics, and antiviral activity of long-acting cabotegravir (CAB LA) plus the broadly neutralizing monoclonal antibody, VRC-HIVMAB080-00-AB (VRC01LS), in adults living with HIV-1 with suppressed plasma viremia.

Condition Intervention Phase
HIV Infections

Drug : Oral Cabotegravir (CAB)
Drug : Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
Drug : Long-Acting Injectable Cabotegravir (CAB LA)
Biological : VRC01LS
Drug : Standard of Care (SOC) Oral ART
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Study of Long-Acting Cabotegravir Plus VRC01LS to Maintain Viral Suppression in Adults Living With HIV-1

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures

  • Frequency of either 1) the occurrence of a Grade 3 or higher adverse event (AE); or 2) premature study treatment discontinuation due to an AE (regardless of grade) [ Time Frame: Measured through Week 48 of Step 2 ]
    Both of which are possibly, probably, or definitely related (as judged by the core team) to the CAB LA plus VRC01LS combination.
  • Number of participants who experience virologic failure [ Time Frame: Measured through Week 44 of Step 2 ]
    Defined as confirmed HIV-1 RNA greater than or equal to 200 copies/mL
Secondary Outcome Measures:
  • Trough levels of the concentration of VRC01LS [ Time Frame: Measured through Week 48 of Step 2 ]
    Based on PK sampling
  • Trough levels of the concentration of CAB LA [ Time Frame: Measured through Week 48 of Step 2 ]
    Based on PK sampling
  • Frequency of viral resistance of breakthrough isolates [ Time Frame: Measured through Week 44 of Step 2 ]
    Based on laboratory evaluations
  • Number of participants who experience virologic failure [ Time Frame: Measured through Week 24 of Step 2 ]
    Defined as confirmed HIV-1 RNA greater than or equal to 200 copies/mL
  • Frequency of either 1) virologic failure (confirmed HIV-1 RNA greater than or equal to 200 copies/mL); or 2) premature discontinuation of the CAB LA plus VRC01LS combination [ Time Frame: Measured through Week 44 of Step 2 ]
    Based on laboratory evaluations
  • Number of participants with confirmed HIV-1 RNA greater than or equal to 50 copies/mL [ Time Frame: Measured through Week 44 of Step 2 ]
    Based on laboratory evaluations
  • Number of participants with confirmed HIV-1 RNA greater than or equal to 50 copies/mL [ Time Frame: Measured through Week 24 of Step 2 ]
    Based on laboratory evaluations
  • Number of participants with either 1) confirmed HIV-1 RNA greater than or equal to 50 copies/mL; or 2) premature discontinuation of the CAB LA plus VRC01LS combination [ Time Frame: Measured through Week 44 of Step 2 ]
    Based on laboratory evaluations
  • Number of participants who experience virologic failure [ Time Frame: Measured through Week 44 of Step 2 ]
    Defined by the U.S. Food and Drug Administration (FDA) snapshot algorithm
  • Frequency of anti-idiotype antibodies against VRC01LS in samples collected from representative time points throughout the study [ Time Frame: Measured through Week 48 of Step 2 ]
    Based on laboratory evaluations
  • Frequency of either 1) the occurrence of a Grade 3 or higher AE; or 2) premature oral CAB discontinuation due to an AE (regardless of grade) [ Time Frame: Measured through Week 5 of Step 1 ]
    Both of which are possibly, probably, or definitely related (as judged by the core team) to oral CAB.
  • Number of participants who prematurely discontinue oral CAB or the CAB LA plus VRC01LS combination [ Time Frame: Measured through Week 44 of Step 2 ]
    Based on self report
  • Frequency of the occurrence of a Grade 3 or higher AE that is possibly, probably, or definitely related (as judged by the core team) to oral CAB or the CAB LA plus VRC01LS combination [ Time Frame: Measured through Week 48 of Step 2 ]

Estimated Enrollment: 74
Anticipated Study Start Date: November 4, 2019
Estimated Study Completion Date: October 24, 2022
Estimated Primary Completion Date: October 30, 2020 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: CAB LA + VRC01LS
Step 1: CAB administered orally as one 30 mg tablet once daily, plus two NRTIs, for 5 weeks. Step 2: CAB LA loading dose (600 mg) administered as one IM injection at Step 2 entry study visit, and maintenance dose (400 mg), starting at 4 weeks after CAB LA loading dose, and then every 4 weeks through Week 44. VRC01LS (30 mg/kg) administered as an IV infusion starting at Step 2 entry and then every 12 weeks through Week 36. Step 3: SOC oral ART regimen for 48 weeks.
Drug: Oral Cabotegravir (CAB)

30 mg tablets administered orally

Drug: Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

NRTIs will not be provided by the study. Participants will obtain NRTIs outside of the study through routine care.

Drug: Long-Acting Injectable Cabotegravir (CAB LA)

600 mg loading dose followed by 400 mg maintenance doses administered by intramuscular (IM) injection

Biological: VRC01LS

30 mg/kg administered as an intravenous (IV) infusion

Other Name: VRC-HIVMAB080-00-AB
Drug: Standard of Care (SOC) Oral ART

SOC ART will not be provided by the study. Participants will obtain SOC ART outside of the study through routine care.

Detailed Description:

This study will assess the safety, tolerability, pharmacokinetics, and antiviral activity of long-acting cabotegravir (CAB LA) plus the broadly neutralizing monoclonal antibody, VRC-HIVMAB080-00-AB (VRC01LS), in adults living with HIV-1 with suppressed plasma viremia.
The study will be conducted in three steps. At Step 1 entry, all participants will discontinue their current antiretroviral therapy (ART) regimen except for nucleoside reverse transcriptase inhibitors (NRTIs), and initiate oral CAB.
During Step 1, participants tolerating oral CAB plus their current two NRTIs, and displaying viral suppression (HIV-1 RNA <50 copies/mL), will register to Step 2. At entry into Step 2, eligible participants will stop their oral CAB and NRTIs and will receive a VRC01LS infusion plus CAB LA injection. After entry in Step 2, participants will receive CAB LA every 4 weeks through Week 44 plus VRC01LS every 12 weeks through Week 36.
At the last visit in Step 2 (Week 48), or at premature study treatment discontinuation, all participants who received any CAB LA or VRC01LS will enter Step 3 and switch to standard of care (SOC) oral ART for 48 weeks.
Participants will attend a number of study visits throughout the study. Study visits may include a physical examination, clinical assessment, pregnancy testing, and blood and urine collection. Participants will remain in the study for approximately 101 weeks, including approximately 5 weeks in Step 1, 48 weeks in Step 2, followed by 48 weeks in Step 3.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years and older  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

Step 1 Inclusion Criteria

  • 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.
    • NOTE: The term "licensed" refers to a US Food and Drug Administration (FDA)-approved kit, which is required for all IND studies.
    • World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (e.g., indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load.
  • Clinically stable for at least 8 weeks prior to study entry on a three-drug ART regimen that includes a boosted protease inhibitor, a nonnucleoside reverse transcriptase inhibitor (NNRTI), or an integrase inhibitor, plus two NRTIs, with no history of a switch due to virologic failure.
    • NOTE: Previous switches for reasons other than virologic failure prior to screening are allowed.
  • Screening CD4+ cell count greater than or equal to 350 cells/mm^3 obtained within 60 days prior to study entry at any US laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent.
  • All available HIV-1 RNA measurements must be less than 50 copies/mL within the 2 years prior to study entry except as allowed by the note below.
    • NOTE: A single plasma HIV-1 RNA greater than or equal to 50 copies/mL but less than 200 copies/mL is allowed if followed by a subsequent HIV-1 RNA value below 50 copies/mL.
  • Participants must have at least two documented HIV-1 RNA less than 50 copies/mL within 12 months prior to study entry.
    • NOTE: The HIV-1 RNA level obtained at the screening visit can be used as the second measurement, but must meet the requirements of screening plasma HIV-1 RNA criterion below.
  • Screening plasma HIV-1 RNA less than 40 copies/mL by any FDA-approved assay with minimum limit of detection of 40 copies/mL or lower obtained within 60 days prior to study entry by any US laboratory that has a CLIA certification or its equivalent.
  • The following laboratory values obtained within 60 days prior to entry at any US laboratory that has a CLIA certification or its equivalent.
    • Absolute neutrophil count (ANC) greater than or equal to 750/mm^3
    • Hemoglobin greater than or equal to 11.0 g/dL for men or greater than or equal to ~#o2~0 g/dL for women ~#sl~ Platelet count greater than or equal to 100,000/mm^3
    • Calculated creatinine clearance (Cockcroft-Gault formula) greater than or equal to 50 mL/min
    • Aspartate aminotransferase (AST) (SGOT) less than or equal to 2.0 x ULN
    • Alanine aminotransferase (ALT) (SGPT) less than or equal to 2.0 x ULN
  • For females of reproductive potential, negative serum or urine pregnancy test within 48 hours prior to entry by any clinic or laboratory that has a CLIA certification or its equivalent, or is using a point of care (POC)/CLIA-waived test.
    • NOTE A: Reproductive potential is defined as girls who have reached menarche and women who have had menses within the prior 12 months, and have not undergone surgical sterilization. If no menses for a year or longer, the follicle-stimulating hormone (FSH) should be less than or equal to 40 IU/mL to be considered of reproductive potential. If an FSH is not available, and they have not had menses in 24 or more consecutive months, they would be considered not to be of reproductive potential. Women who have undergone surgical sterilization (e.g., hysterectomy, bilateral oophorectomy, tubal micro-inserts, tubal ligation or salpingectomy) are considered not to be of reproductive potential.
    • NOTE B: Participant-reported history of hysterectomy and bilateral oophorectomy, tubal ligation, bilateral salpingectomy, tubal micro-inserts, and menopause is acceptable documentation.
    • Female participants of reproductive potential, who are participating in sexual activity that could lead to pregnancy, must agree to use an effective form of contraception from 30 days prior to the first dose of study medication, while receiving the study drugs, and for 30 days after stopping oral medications, or the duration specified in the product label if receiving study drugs not supplied by the study, or for 52 weeks after last dose of CAB LA or VRC01LS. Acceptable methods of contraception include:
      • Contraceptive subdermal implant
      • Intrauterine device or intrauterine system
      • Combined estrogen and progestogen oral contraceptive
      • Injectable progestogen
      • Contraceptive vaginal ring
      • Percutaneous contraceptive patches
    • Women who are not of reproductive potential are eligible to start study drugs without requiring the use of contraceptives. Refer to above criterion for definition of female who is not of reproductive potential.
    • NOTE: All participants in the study should be counseled on safer sexual practices including the use and benefit/risk of effective barrier methods (e.g., male condom) and on the risk of HIV transmission to an uninfected partner.
  • Men and women aged greater than or equal to 18 years.
  • Ability and willingness of participant to provide written informed consent.
  • Negative HBsAg results obtained within 60 days prior to study entry.
  • Negative hepatitis C virus (HCV) antibody result obtained within 60 days prior to study entry or, if the HCV antibody result is positive, a negative HCV RNA result obtained within 60 days prior to study entry.
  • Susceptibility to VRC01LS based on IC50 less than or equal to 1.0 µg/mL using the Monogram Phenosense Assay on sample obtained at the screening visit.
  • Adequate venous access in at least one arm.
  • Willingness to continue current two NRTIs and have continued access to NRTIs in Step
      • NOTE: NRTIs will not be provided by the study. Participants without continued access to NRTIs will be provided reimbursement for these drugs by the study.
    1. Willingness to not actively engage in the conception process for the duration of the study.

    Step 1 Exclusion Criteria
  • Any previous receipt of humanized or human monoclonal antibody (licensed or investigational).
  • Weight greater than 115 kg or less than 53 kg.
  • Acute or ongoing AIDS-defining illness within 60 days prior to study entry.
  • History of a severe allergic reaction with generalized urticarial, angioedema, or anaphylaxis within 2 years prior to study entry.
  • Currently breastfeeding or pregnant.
  • Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
  • Acute or serious illness that, in the opinion of the site investigator, requires systemic treatment and/or hospitalization within 60 days prior to entry.
  • Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 60 days prior to study entry.
    • NOTE: Participants receiving stable physiologic doses of glucocorticoids, defined as the equivalent of prednisone less than or equal to 10 mg/day, will not be excluded. Stable physiologic glucocorticoid doses should not be discontinued for the duration of the study. In addition, participants receiving inhaled or topical corticosteroids will not be excluded.
  • Treatment for hepatitis C within 24 weeks prior to study entry.
  • Vaccinations within 7 days prior to study entry.
    • NOTE: Participants are encouraged to get routine vaccinations, such as seasonal influenza vaccine outside this window. If vaccination occurs within 7 days prior to study entry, the entry visit should be postponed for at least 7 days after the vaccination.
  • Initiation of ART during acute HIV-1 infection (as determined by the site investigator by history and/or available medical records).
  • Personal or known family history of prolonged QT syndrome or a clinically significant finding on the screening electrocardiogram (ECG).
  • Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • Moderate or severe hepatic impairment (Class B or C) as determined by Child-Pugh classification.
  • History of seizures or treatment for seizures within the past 2 years prior to study entry.
    • NOTE: For candidates with a remote (greater than 2 year) history of seizure, consult the A5357 protocol core team for eligibility determination.

    • Step 2 Inclusion Criteria
  • HIV-1 RNA less than 50 copies/mL at week 4 (Step 1), or HIV-1 RNA of 50-199 copies/mL at week 4 followed by HIV-1 RNA less than 50 copies/mL at week 5 (Step 1).
  • Females of reproductive potential must have a negative serum or urine pregnancy test obtained within 48 hours prior to Step 2 registration.
    • NOTE: Refer to the criteria above for definition of reproductive potential and acceptable documentation.
  • Female participant agrees to continue to use an effective form of contraception (see criterion above) while on study, and for 52 weeks after last dose of CAB LA or VRC01LS.
  • Willingness to not actively engage in the conception process for the duration of the study.

  • Step 2 Exclusion Criteria
  • Discontinuation or temporary hold of oral CAB for greater than 7 consecutive days for any reason during Step 1.
  • Discontinuation or temporary hold of NRTIs for greater than 7 consecutive days for any reason during Step 1.
  • Grade 3 or 4 adverse event thought to be related to oral CAB during Step 1 according to the site investigator.
  • Vaccination (e.g., influenza) within 7 days prior to the Step 2 registration.
    • NOTE: Vaccination should also be avoided when possible within 7 days of the week 44 and week 48 visits.
  • Currently breastfeeding or pregnant.
  • Any greater than or equal to Grade 2 ALT (greater than 2.5 times ULN) that developed during Step 1.

  • Step 3 Inclusion Criterion
  • Received any CAB LA or VRC01LS during Step 2.
    • NOTE: Participants who prematurely discontinue study treatment for any reason in Step 2 remain eligible for Step 3.

    • Step 3 Exclusion Criterion
  • There are no exclusion criteria to Step 3.

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03739996

Locations

United States, California
UCLA CARE Center CRS Not yet recruiting
Los Angeles, California, United States, 90035
Contact: Aleen Khodabakhshian    310-557-9027    akhodabakhshian@mednet.ucla.edu
UCSD Antiviral Research Center CRS Not yet recruiting
San Diego, California, United States, 92103
Contact: Steven Hendrickx, R.N.    619-543-6968    smhendrickx@ucsd.edu
Ucsf Hiv/Aids Crs Not yet recruiting
San Francisco, California, United States, 94110
Contact: Jay Dwyer    415-476-4082 ext 353    Jay.Dwyer@ucsf.edu
Harbor-UCLA CRS Not yet recruiting
Torrance, California, United States, 90502
Contact: Mario Guerrero    424-201-3000 ext 7318    mguerrero@labiomed.org
United States, Colorado
University of Colorado Hospital CRS Not yet recruiting
Aurora, Colorado, United States, 80045
Contact: Suzanne Fiorillo, M.S.P.H.    303-724-5931    suzanne.fiorillo@ucdenver.edu
United States, Georgia
The Ponce de Leon Center CRS Not yet recruiting
Atlanta, Georgia, United States, 30308-2012
Contact: Ericka Patrick, M.S.N.    404-616-6313    erpatri@emory.edu
United States, Illinois
Northwestern University CRS Not yet recruiting
Chicago, Illinois, United States, 60611
Contact: Baiba Berzins, M.P.H.    312-695-5012    Baiba@northwestern.edu
United States, Maryland
Johns Hopkins University CRS Not yet recruiting
Baltimore, Maryland, United States, 21205
Contact: Ilene Wiggins, R.N.    410-614-2766    iwiggin1@jhmi.edu
United States, Massachusetts
Massachusetts General Hospital CRS (MGH CRS) Not yet recruiting
Boston, Massachusetts, United States, 02114
Contact: Theresa Flynn, R.N., M.S.N., A.N.P., B.S.N.    617-724-0072    tflynn@partners.org
Brigham and Women's Hospital Therapeutics Clinical Research Site (BWH TCRS) CRS Not yet recruiting
Boston, Massachusetts, United States, 02115
Contact: Cheryl E. Keenan, R.N.    617-732-5635    CKeenan@BWH.Harvard.edu
United States, New York
Weill Cornell Chelsea CRS Not yet recruiting
New York, New York, United States, 10010
Contact: Todd Stroberg, R.N., B.S.N.    212-746-7198    tstrober@med.cornell.edu
Columbia P&S CRS Not yet recruiting
New York, New York, United States, 10032-3732
Contact: Steven Palmer, P.A. -C    212-342-2958    sp500@cumc.columbia.edu
Weill Cornell Uptown CRS Not yet recruiting
New York, New York, United States, 10065
Contact: Rebecca Fry, M.S.N., FNP    212-746-4166    ref2007@med.cornell.edu
United States, North Carolina
Chapel Hill CRS Not yet recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Becky Straub, B.S.N., M.P.H., R.N.    919-843-9975    bstraub@med.unc.edu
United States, Ohio
Ohio State University CRS Not yet recruiting
Columbus, Ohio, United States, 43210
Contact: Kathy Watson, B.S.N., R.N.    614-293-5856    kathy.watson@osumc.edu
United States, Pennsylvania
University of Pittsburgh CRS Not yet recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Dawn R. Weinman    412-383-1748    drw38@pitt.edu
Puerto Rico
Puerto Rico AIDS Clinical Trials Unit CRS Not yet recruiting
San Juan, Puerto Rico, 00935
Contact: Sylvia I. Davila Nieves, M.Sc.    787-767-9192    sylvia.davila1@upr.edu

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)
ViiV

Investigators

Study Chair: Babafemi Taiwo, MBBS Northwestern University CRS
Study Chair: Pablo Tebas, MD Hospital of the University of Pennsylvania CRS
Study Chair: Leah Burke, MD Weill Cornell Chelsea CRS
More Information

More Information


Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)  
ClinicalTrials.gov Identifier: NCT03739996   History of Changes  
Other Study ID Numbers: ACTG A5357  
  30005  
Study First Received: November 9, 2018  
Last Updated: July 22, 2019  
Individual Participant Data    
Plan to Share IPD: Yes  

Studies a U.S. FDA-regulated Drug Product: Yes  
Studies a U.S. FDA-regulated Device Product: No  

Additional relevant MeSH terms:
HIV Infections
Reverse Transcriptase Inhibitors

ClinicalTrials.gov processed this data on October 15, 2019
This information is provided by ClinicalTrials.gov.