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Clinical Trials

MainTitle

Safety and Efficacy of Fixed Dose Combination Dolutegravir/Abacavir/Lamivudine FDC Initiated During Acute HIV Infection (PHI 05)

This study is currently recruiting participants. (see Contacts and Locations)

Verified May 2017 by University of North Carolina, Chapel Hill

Sponsor
University of North Carolina, Chapel Hill

Collaborator
ViiV Healthcare
National Cancer Institute (NCI)

Information provided by (Responsible Party)
University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier
NCT02384395

First received: March 4, 2015
Last updated: May 15, 2017
Last Verified: May 2017
History of Changes
Purpose

Purpose

This is a multicenter, single arm, 96-week open-label study of the safety and virologic efficacy of fixed dose combination Dolutegravir/Lamivudine/Abacavir (DTG/3TC/ABC FDC) initiated during acute HIV infection (AHI).

Condition Intervention
HIV
Acute HIV Infection

Drug : DTG/3TC/ABC FDC

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: IGHID 11417 - The Safety and Efficacy of Fixed Dose Combination Dolutegravir/Abacavir/Lamivudine FDC Initiated During Acute HIV Infection: Impact on the Latent HIV Reservoir and Long-Term Immunologic Effect

Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures

  • Viral load measurement of <200 copies/mL [ Time Frame: week 24 ]
Secondary Outcome Measures:
  • Occurrence of Grade 3 or higher adverse event (AE) [ Time Frame: baseline through week 96 ]
    sign/symptom, lab toxicity, or clinical events, or Grade 1 or higher AE that is definitely, probably, or possibly related to study treatment
  • Virologic efficacy of DTG/3TC/ABC FDC given once daily to participants with acute HIV as determined by the proportion of treated participants with HIV-1 RNA to <50 copies/mL [ Time Frame: week 48 ]
  • Rate of virologic decline in the first 24 weeks of treatment [ Time Frame: week 24 ]

Estimated Enrollment: 40
Study Start Date: September 2015
Estimated Study Completion Date: January 2019
Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: DTG/3TC/ABC FDC
Dolutegravir (DTG 50 mg), abacavir sulfate (ABC 600 mg) and lamivudine (3TC 300 mg) formulated in a single tablet fixed dose combination (FDC) (DTG/ABC/3TC, GSK2619619), administered orally, once daily
Drug: DTG/3TC/ABC FDC

DTG/3TC/ABC FDC as initial therapy for AHI

Other Name:
  • Dolutegravir
  • abacavir sulfate
  • lamivudine

Detailed Description:

The study will be conducted at the University of North Carolina in Chapel Hill, NC and Duke University in Durham, NC. All forty (40) participants will be enrolled for 96 weeks and will receive DTG/3TC/ABC FDC.
We propose to evaluate the efficacy and time to viral suppression with DTG/3TC/ABC FDC as initial therapy for AHI (acute HIV infection), as well as the feasibility of prompt administration using a rapid HLA-B57 (human leukocyte antigen) screening antibody assay. In addition to validating the restriction of RCI (resting cell infection) by ART (antiretroviral therapy) including a DTG-based regimen initiated during AHI, we will seek correlations between low RCI, residual GALT (gastrointestinal associated lymphoid tissue) HIV expression, and measures of immune activation. We hypothesize that rapid reduction in plasma viremia with this regimen will limit the area under the pre-ART viral load curve, and thus reduce the latent reservoir size as measured by a viral outgrowth assay one to two years following ART start, and as compared with the latent reservoir size in acutely infected individuals started on regimens without an integrase inhibitor based regimen. In addition, we will examine the longitudinal impact of the proposed integrase-based regimen initiated during the acute period on immune activation through week 96. If residual viral expression and persistent immune dysfunction is related to the burden of the latent viral reservoir (and presumably its periodic activation) these abnormalities should be ameliorated by early ART with rapid viral suppression. Finally, we will evaluate dolutegravir levels in plasma and GALT and whether rapid viral suppression with the proposed dolutegravir-based ART regimen impacts HIV RNA levels in GALT.

Eligibility

Eligibility

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

Criteria

Inclusion Criteria

  1. Documentation of Acute HIV infection at or within 30 days of study entry.
  2. Men and women age ≥18 years.
  3. ART naive, defined as ≤14 days of antiretroviral treatment at any time prior to entry. The only exceptions are:
    • Pre-exposure prophylaxis (PrEP) and documented as HIV-1 negative at least 1 month prior to AHI diagnosis during PrEP, and
    • Post-exposure prophylaxis (PEP) provided the participant was documented as HIV-1 negative at least 3-6 months following completion of PEP treatment.
  4. Lab values obtained within 30 days prior to study entry:
    • Absolute neutrophil count >500/mm3
    • Hemoglobin > 8.5 g/dL for men and > 8.0 g/dL for women
    • Platelet count >50,000/mm3
    • Lipase ≤ 3 X upper limit of normal (ULN), single repeat test is allowed to determine eligibility
    • Calculated creatinine clearance (Cockcroft-Gault formula) ≥ 50mL/min:

CrCl = (140-age) x body weight (kg) (x 0.85 if female) Serum creatinine [mg/dL] x (72)
  • Testing for HBsAg is pending. Note: Participants who test positive for HBsAg will be terminated from the study prior to starting study treatment.
  • Testing for HLA-B57 and/or HLA-B*5701 is pending. Note: Participants who test positive for HLA-B*5701 will be terminated from the study prior to starting study treatment.
  • A female is eligible to enter and participate in the study if she:
    • Is of non-childbearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥ 45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy; or,
    • Is of child-bearing potential, with a negative pregnancy test at screening and at enrollment, who agrees to use one of the methods of contraception listed below.
    • Complete abstinence from intercourse from 2 weeks prior to administration of study medication, throughout the study, and for at least 2 weeks after discontinuation of all study medication;
    • Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide);
    • Approved hormonal contraception - used alone is not considered a sufficient form of contraception for the study see Protocol Appendix 1 for a listing of examples of approved hormonal contraception;
    • Any intrauterine device (IUD) with published data showing that the expected failure rate is <1% per year; see Protocol Appendix 2 for a listing of IUDs meeting this criterion;
    • Male partner sterilization confirmed prior to the female participant's entry into the study, and this male is the sole partner for that patient;
    • Any other method with published data showing that the expected failure rate is <1% per year.
    • Any contraception method must be used consistently, in accordance with the approved product label and for at least 2 weeks after discontinuation of the study medication.
  • Ability and willingness of participant to give written informed consent.

  • Exclusion Criteria
  • ALT ≥ 5 times Upper Limit of Normal (≥5xULN)
  • AST ≥ 3x ULN
  • Bilirubin ≥1.5x ULN (with >35% direct bilirubin)
  • Women who are breast-feeding.
  • Women with a positive pregnancy test on enrollment or prior to study drug administration.
  • History or presence of allergy to the study drugs or their components.
  • Requires or is anticipated to require any of the prohibited concomitant therapy: barbiturates, dofetilide, modafinil, oxcarbazepine, pioglitazone, pimozide, rifampin, rifapentine, phenytoin, phenobarbital, carbamazepine, and St. John's wort.
    • Dofetilide is prohibited, as DTG may inhibit its renal tubular secretion resulting in increased dofetilide concentrations and potential for toxicity.
  • Unable to discontinue any current medications that are excluded during study treatment.
  • Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), radiation therapy, HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry.
    • Prednisone at a daily dose of 10 mg or less (physiologic replacement dose) is permitted.
  • Treatment with radiation therapy or cytotoxic chemotherapeutics agents within 28 days prior to screening or has an anticipated need for these agents during the study.
  • Administration of an HIV-1 immunotherapeutic vaccine within 90 days prior to screening.
  • Prior treatment with any other experimental drug for any indication (within 30 days of initiating study treatment).
  • Difficulty swallowing capsules/tablets.
  • Inability to communicate effectively with study personnel.
  • Incarceration; prisoner recruitment and participation are not permitted.
  • Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements or confound the analysis of study endpoints.
  • Any condition (including but not limited to alcohol and drug use) or any active clinically significant disease or findings during screening of medical history or physical examination, which, in the opinion of the Investigator would interfere with patient safety or compliance.
  • Serious illness requiring systemic treatment and/or hospitalization until patient either completes therapy or is clinically stable on therapy, in the opinion of the site investigator, for at least 7 days prior to study entry.

  • NOTE: Oral candidiasis, vaginal candidiasis, mucocutaneous herpes simplex, and other minor illnesses (as judged by the site investigator) have no restriction.
  • A life expectancy less than twelve months.
  • Acute viral hepatitis, including, but not limited to, hepatitis A, B, or C.
  • History of myocardial infarction or diagnosis of coronary artery disease.
  • History of ongoing or clinically relevant pancreatitis within the previous 6 months.
  • Chronic hepatitis C infection with an anticipated need for treatment during the study period (through week 96).
  • Chronic hepatitis B infection (see inclusion criteria 5).
  • Evidence for moderate to severe hepatic impairment (as defined by the presence of cirrhosis, ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice or Child-Pugh class B or greater hepatic impairment).
  • Evidence of biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • Any verified grade 4 laboratory abnormality with exception of ALT as defined in exclusion criteria 1

    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: NCT02384395

    Contacts

    Contact:   JoAnn Kuruc, MSN, RN 919-966-8533 joann_kuruc@med.unc.edu
    Contact:   Kristen Hancock, RN 919-843-6848 kristen_hancock@med.unc.edu

    Locations

    United States, North Carolina
    University of North Carolina Recruiting
    Chapel Hill, North Carolina, United States, 27599
    Duke University Health System Recruiting
    Durham, North Carolina, United States, 27710
    Contact: Kara McGee, MSPH, PA-C    919-668-0242    kara.mcgee@duke.edu
    Principal Investigator: Mehri McKellar, MD

    Sponsors and Collaborators

    University of North Carolina, Chapel Hill
    ViiV Healthcare
    National Cancer Institute (NCI)

    Investigators

    Principal Investigator: Cindy Gay, MD, MPH University of North Carolina
    More Information

    More Information

    Additional Information:

    University of North Carolina website

    Responsible Party: University of North Carolina, Chapel Hill  
    ClinicalTrials.gov Identifier: NCT02384395   History of Changes  
    Other Study ID Numbers: 14-0549  
    Study First Received: March 4, 2015  
    Last Updated: May 15, 2017  
    Individual Participant Data    
    Plan to Share IPD: No  

    Keywords provided by University of North Carolina, Chapel Hill:

    Dolutegravir
    Abacavir
    Lamivudine
    acute HIV infection
    human leukocyte antigen
    latent HIV reservoir
    integrase-based regimen
    viremia
    antiretroviral therapy
    fixed dose combination

    Additional relevant MeSH terms:
    Infection
    Communicable Diseases
    HIV Infections
    Acquired Immunodeficiency Syndrome
    Lamivudine
    Abacavir
    Dideoxynucleosides
    Dolutegravir

    ClinicalTrials.gov processed this data on October 19, 2017
    This information is provided by ClinicalTrials.gov.