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

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ClinicalTrials.gov Identifier: NCT02384395
Recruitment Status : Recruiting
First Posted : March 10, 2015
Last Update Posted : April 19, 2019
Sponsor:
Collaborator:
ViiV Healthcare
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill

Brief Summary:
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 or disease Intervention/treatment Phase
HIV Acute HIV Infection Drug: DTG/3TC/ABC FDC Not Applicable

Detailed Description:

The study will be conducted at the University of North Carolina in Chapel Hill, NC and Duke University in Durham, NC. We plan to enroll up to 44 participants who 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. We hypothesize that earlier treatment coupled with more rapid ART-mediated virus suppression will be associated with better long-term T cell function, specifically better T cell function after 2 years of durable HIV suppression.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 44 participants
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
Study Start Date : September 2015
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : July 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
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 Names:
  • Dolutegravir
  • abacavir sulfate
  • lamivudine




Primary Outcome Measures :
  1. Viral load measurement of <200 copies/mL [ Time Frame: week 24 ]

Secondary Outcome Measures :
  1. 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

  2. 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 ]
  3. Rate of virologic decline in the first 24 weeks of treatment [ Time Frame: week 24 ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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)

  5. Testing for HBsAg is pending. Note: Participants who test positive for HBsAg will be terminated from the study prior to starting study treatment.
  6. 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.
  7. 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.
  8. Females who meet the post-menopausal definition, noted in inclusion criterion 7, will have a follicle stimulation hormone (FSH) test to verify menopause,
  9. Ability and willingness of participant to give written informed consent.

Exclusion Criteria

  1. ALT ≥ 5 times Upper Limit of Normal (≥5xULN)
  2. AST ≥ 3x ULN
  3. Bilirubin ≥1.5x ULN (with >35% direct bilirubin)
  4. Weight <40 kg
  5. Women who are breast-feeding.
  6. Women with a positive pregnancy test on enrollment or prior to study drug administration.
  7. Women and men of child bearing potential unwilling to agree to use an effective methods of contraception required by the study.
  8. History or presence of allergy to the study drugs or their components.
  9. Requires or is anticipated to require any of the prohibited concomitant therapy: barbiturates, dofetilide, modafinil, oxcarbazepine, pioglitazone, pilsicainide, pimozide, rifampin, rifapentine, phenytoin, phenobarbital, carbamazepine, and St. John's wort.

    • Dofetilide and pilsicainide are prohibited, as DTG may inhibit its renal tubular secretion resulting in increased dofetilide concentrations and potential for toxicity.
  10. Unable to discontinue any current medications that are excluded during study treatment.
  11. 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.
  12. 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.
  13. Administration of an HIV-1 immunotherapeutic vaccine within 90 days prior to screening.
  14. Prior treatment with any other experimental drug for any indication (within 30 days of initiating study treatment).
  15. Difficulty swallowing capsules/tablets.
  16. Inability to communicate effectively with study personnel.
  17. Incarceration; prisoner recruitment and participation are not permitted.
  18. 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.
  19. 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.
  20. 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.

  21. A life expectancy less than twelve months.
  22. Acute viral hepatitis, including, but not limited to, hepatitis A, B, or C.
  23. History of myocardial infarction or diagnosis of coronary artery disease.
  24. History of ongoing or clinically relevant pancreatitis within the previous 6 months.
  25. Chronic hepatitis C infection with an anticipated need for treatment during the study period (through week 96).
  26. Chronic hepatitis B infection (see inclusion criterion 5).
  27. 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).
  28. Evidence of biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  29. Any verified grade 4 laboratory abnormality with exception of ALT as defined in exclusion criterion 1

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02384395


Contacts
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Contact: JoAnn Kuruc, MSN, RN 919-966-8533 joann_kuruc@med.unc.edu
Contact: Susan Blevins, ANP 919-843-8763 suzanne_blevins@med.unc.edu

Locations
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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
Investigators
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Principal Investigator: Cindy Gay, MD, MPH University of North Carolina

Additional Information:
Publications:
Adolescents. PoAGfAa. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. In: Department of Health and Human Servies.; 2013
Walmsley SL, Berenguer J, Kuong-Josses M-A, Kilby JM, Lutz T, Podzamczer D, et al. Dolutegravir Regimen Statistically Superior to Efavirenz/Tenofovir/Emtricitabine: 96-Week Results From the SINGLE Study (ING114467) In: 21st Conference on Retroviruses and Opportunistic Infections. Boston, MA; 2014.

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Responsible Party: University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT02384395     History of Changes
Other Study ID Numbers: 14-0549
First Posted: March 10, 2015    Key Record Dates
Last Update Posted: April 19, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
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:
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Lamivudine
Infection
Communicable Diseases
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Abacavir
Dideoxynucleosides
Dolutegravir
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Anti-HIV Agents
HIV Integrase Inhibitors
Integrase Inhibitors
Antimetabolites