Clinical Trials

MainTitle

Rapid Test and Treat Dolutegravir Plus Lamivudine Study in Newly Diagnosed Human Immunodeficiency Virus (HIV)-1 Infected Adults

This study is ongoing, but not recruiting participants.
Sponsor
ViiV Healthcare


Information provided by (Responsible Party)
ViiV Healthcare
ClinicalTrials.gov Identifier
NCT03945981

First received: May 8, 2019
Last updated: May 5, 2020
Last Verified: May 2020
History of Changes
Purpose

Purpose

Early initiation of antiretroviral therapy (ART) reduces morbidity and mortality for individuals infected with HIV. Suppressing viral replication with ART also reduces the potential for transmission of HIV. Hence, ART is recommended for all persons with HIV viremia regardless of cluster of differentiation 4 (CD4) count. This is an open-label single arm which will evaluate the feasibility, efficacy and safety using a fixed dose combination (FDC) of Dolutegravir (DTG) plus Lamivudine (3TC) as a first line regimen of a rapid Test and Treat model of care over 48 weeks. Participants with new and confirmed diagnosed HIV-1 who are willing to start study treatment immediately following diagnosis will receive 50 milligram (mg) DTG + 300 (mg) 3TC FDC as first line therapy without waiting for screening laboratory results, at the Screening/Day 1 Visit. The total duration for the study will be 52 weeks and 4 weeks of follow up period if required. This study will be conducted in United States (US) with approximately 120 participants.

Condition Intervention Phase
HIV Infections

Drug : Dolutegravir + Lamivudine FDC
Phase 3

Study Type: Interventional
Study Design: Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Participants will receive 50 mg DTG + 300 mg 3TC FDC, participants will administer one tablet once daily (OD) orally with or without food.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3b Multi-center, Open Label, Single Arm, 52-week Study, Evaluating the Feasibility, Efficacy and Safety of Rapid Test and Treat Intervention in Newly Diagnosed HIV-1 Infected Adults Using a Fixed Dose Combination of Dolutegravir Plus Lamivudine (DOVATO) as a First Line Regimen

Further study details as provided by ViiV Healthcare:

Primary Outcome Measures

  • Number of Participants with plasma HIV-1 Ribonucleic acid (RNA) less than 50 copy/milliliter (c/mL) regardless of ART regimen (observed analysis) [ Time Frame: At Week 24 ]
    Blood samples will be collected to assess the number of participants with plasma HIV-1 RNA less than 50 c/mL analyzed with observed analysis.
Secondary Outcome Measures:
  • Number of participants who have HIV-RNA less than 50 c/mL regardless of ART regimen (observed analysis) [ Time Frame: At Week 48 ]
    Blood samples will be collected to assess the number of participants with plasma HIV-1 RNA less than 50 c/mL analyzed with observed analysis.
  • Number of participants with plasma HIV-1 RNA less than 50 c/mL using the FDA Snapshot algorithm [ Time Frame: At Weeks 24 and 48 ]
    Blood samples will be collected to assess the number of participants with plasma HIV-1 RNA less than 50 c/mL analyzed with FDA snapshot algorithm.
  • Time to suppression of HIV-1 RNA less than 50 c/mL [ Time Frame: Up to Week 48 ]
    Participants reaching viral suppression HIV-1 RNA less than 50 c/mL will be analyzed at given time points
  • Number of participants who change first line regimen of DTG + 3TC FDC due to Baseline laboratory or HIV-1 resistance mutation results [ Time Frame: Up to Week 48 ]
    Participants who change the first line regimen of DTG + 3TC FDC due to Baseline laboratory or HIV-1 resistance mutation results will be analyzed at given time points
  • Number of participants with treatment-emergent genotypic resistance to DTG and/or 3TC, or any other ART if treatment is modified, in participants meeting confirmed virologic failure criteria [ Time Frame: Up to Week 52 ]
    Blood samples will be collected for genotypic and phenotypic analyses at given time point. These may be analyzed by Monogram Biosciences using, but not limited to, their Standard PhenoSense and GenoSure testing methods for protease (PRO), reverse transcriptase (RT), and integrase assays. This assessment will be performed for participants meeting virologic failure criteria
  • Number of participants with treatment-emergent phenotypic resistance to DTG and/or 3TC, or any other ART treatment, modified, in participants meeting confirmed virologic failure criteria [ Time Frame: Up to Week 48 ]
    Blood samples will be collected for genotypic and phenotypic analyses at given time point. This will be analyzed by Monogram Biosciences using, but not limited to, their Standard PhenoSense and GenoSure testing methods for protease (PRO), reverse transcriptase (RT), and integrase assays. This assessment will performed for participants with meeting confirmed virologic failure criteria
  • Number of participants with adverse events (AEs) [ Time Frame: Up to Week 52 ]
    An AE is any untoward medical occurrence in a study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product
  • Severity of AEs [ Time Frame: Up to Week 52 ]
    Assessment of severity and intensity for each AE will be reported during the study. Intensity will be performed based on the division of acquired immune deficiency syndrome (AIDS) Table for Grading the Severity of Adult and Pediatric AEs (Division of AIDS [DAIDS] AE Grading Table)
  • Number of participants with abnormal hematology parameters [ Time Frame: Up to Week 48 ]
    Blood sample will be collected to measure laboratory parameters such as platelet count, red blood cells (RBC) count, white blood cells (WBC) count (absolute), haemoglobin (Hb), hematocrit, mean corpuscular volume (MCV), mean corpuscular Hb (MCH), neutrophils, lymphocytes, monocytes, eosinophils, basophils
  • Number of participants with abnormal chemistry parameters [ Time Frame: Up to Week 48 ]
    Blood sample will be collected to measure laboratory parameters such as blood urea nitrogen (BUN), creatinine, glucose, sodium, calcium, potassium chloride, total carbon dioxide (CO2), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, phosphate, protein, total bilirubin, direct bilirubin, albumin, glomerular Filtration rate (GFR)/creatinine clearance, cystatin-C
  • Number of participants with abnormal urinalysis parameters [ Time Frame: Up to Week 48 ]
    Urine sample will be collected to measure urinalysis parameters such as specific gravity, power of hydrogen (pH), glucose, protein, blood and ketones by dipstick (with microscopic examination if blood or protein is abnormal), urine albumin/creatinine ratio, urine protein/creatinine ratio
  • Number of participants who discontinued the treatment due to AEs [ Time Frame: Up to Week 48 ]
    Number of participants who will discontinue the treatment due to AEs will be analyzed
  • Number of participants who discontinued the treatment due to drug-related AEs [ Time Frame: Up to Week 48 ]
    Number of participants who will discontinue the treatment due to drug-related AEs will be analyzed
  • Change from Baseline in CD4+ cell counts [ Time Frame: Baseline (Day 1), Week 24 and 48 ]
    Blood samples will be collected at indicated time points
  • Change from Baseline in CD4+/ cluster of differentiation 8 (CD8)+ ratio [ Time Frame: Baseline (Day 1), Week 24 and 48 ]
    Blood samples will be collected at indicated time points
  • Number of participants who complete their visit [ Time Frame: At Weeks 24 and 48 ]
    Number of participants who will complete their visit at given time point will be analyzed
  • Number of participants who complete their visit with HIV-1 RNA less than 200 c/mL [ Time Frame: At Weeks 24 and 48 ]
    Number of participants who complete their visit with HIV-1 RNA less than 200 c/mL will be analyzed at given time points

Enrollment: 128
Study Start Date: July 2, 2019
Estimated Study Completion Date: October 30, 2020
Estimated Primary Completion Date: April 27, 2020 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: Participants receiving Dolutegravir + Lamivudine FDC
Participants will receive DTG 50mg and 3TC 300 mg FDC tablet orally once daily (OD) with or without food
Drug: Dolutegravir + Lamivudine FDC

Dolutegravir + Lamivudine FDC is available as white oval film-coated tablets which are packed in high density polyethylene (HDPE) bottles with induction seals and child-resistant closures. Each 60 milliliter (mL) bottle contains 30 tablets

Eligibility

Eligibility

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

Criteria

Inclusion Criteria:

  • Eligible participants must be able to understand and comply with protocol requirements, instructions, and restrictions.
  • Eligible participants must be likely to complete the study as planned.
  • Eligible participants must be considered appropriate candidates for participation in an investigative clinical trial with oral medication (e.g. no active problematic substance abuse, acute major organ disease, or potential long-term work assignments out of the country).
  • Participant must be more than or equal to 18 at the time of signing the informed consent.
  • Participants must have a new and confirmed diagnosis of HIV-1 infection and are willing to initiate ART immediately (or, for those participants referred from another site, within 14 days of initial diagnosis at the external clinic/testing center).
  • Participant must have an initial positive rapid HIV test and participant has a second positive confirmatory rapid HIV test, using a test kit from a different manufacturer than the first test or participant has been identified as HIV-1 infected using an FDA-approved 4th generation assay antigen/antibody combination immunoassay or 3rd generation immunoassay that detects and differentiates HIV-1 and HIV-2 antibodies; participant has a confirmatory HIV western blot or an HIV-1 RNA or participant has a positive FDA-approved 4th generation assay and a positive 3rd generation immunoassay that detects and differentiates HIV-1 and HIV-2 antibodies.
  • Antiretroviral-naïve. Participants who received HIV post-exposure prophylaxis (PEP) or pre-exposure prophylaxis (PrEP) in the past are allowed as long as the last PEP/PrEP dose was more than 6 months from HIV diagnosis or there is documented HIV seronegativity at least 2 months after the last prophylactic dose and prior to the date of HIV diagnosis.
  • Male and/or female participants.
  • Participants who are female at birth are eligible to participate if at least one of the following conditions applies: Not pregnant [as confirmed by a negative urine human chorionic gonadotropin (hCG) test at Screening/Day 1.
  • Pregnant and post the first trimester (the physician and patient should decide whether enrolling in this study is in the participants best interest during the consent process)
  • Not a participant of childbearing potential (POCBP) or a POCBP agrees to follow the contraceptive guidance, is currently taking hormonal contraceptives and continues for at least 2 weeks after the last dose of study medication. Participants who are female at birth and who are in the following categories are not considered POCBP, premenarchal, premenopausal female with one of the following: documented hysterectomy, documented bilateral salpingectomy, documented bilateral oophorectomy or postmenopausal, a postmenopausal state is defined as no menses for 12 months without an alternative medical cause; a high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in participants who are female at birth and not using hormonal contraception or hormonal replacement therapy (HRT); participants who are female at birth on HRT and whose menopausal status is in doubt will be required to use one of the non-hormonal highly effective contraception methods if they wish to continue their HRT during the study.
  • Participants who are capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.


Exclusion Criteria:
  • Participants who are breastfeeding, plan to become pregnant or breastfeed during the study.
  • Participants who are in their first trimester of pregnancy.
  • HIV-1 drug resistance genotype test results are known prior to Screening/Day 1.
  • Any evidence of an active Centers for Disease Control and Prevention (CDC) Stage 3 disease except for esophageal candidiasis and cutaneous Kaposi's sarcoma not requiring systemic therapy.
  • Participants with known or suspected Hepatitis B infection.
  • Participants with known or suspected severe hepatic impairment or unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • Participants with known moderate to severe renal impairment (creatinine clearance less than 30ml/minute per 1.73 square meter);
  • Participant with ongoing malignancy other than basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical, anal or penile intraepithelial neoplasia; other localized malignancies require agreement between the investigator and the Study Medical Monitor for inclusion of the participant.
  • Participants who in the investigator's judgment, poses a significant suicidality risk.
  • Participants with any pre-existing physical or mental condition which, in the opinion of the Investigator, may interfere with the participant's ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the participant.
  • Participants with substance abuse disorders or social restraints that the Investigator considers to be possible deterrents to successful initiation of ART.
  • Participants with history or presence of allergy or intolerance to the study drugs or their components.
  • Participants with treatment with any of the following agents within 28 days of the first dose of study treatment, radiation therapy, cytotoxic chemotherapeutic agents, any systemic immune suppressant.
  • Participants receiving any prohibited medication and who are unwilling or unable to switch to an alternate medication.
  • Exposure to an experimental drug or experimental vaccine within either 28 days, 5
half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to the first dose of study treatment.

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: NCT03945981

Locations

United States, Alabama
GSK Investigational Site
Birmingham, Alabama, United States, 35294
United States, California
GSK Investigational Site
Los Angeles, California, United States, 90036
GSK Investigational Site
Palm Springs, California, United States, 92262
United States, Florida
GSK Investigational Site
Fort Pierce, Florida, United States, 34982
GSK Investigational Site
Miami, Florida, United States, 33136
GSK Investigational Site
Oakland Park, Florida, United States, 33334
GSK Investigational Site
Orlando, Florida, United States, 32803
GSK Investigational Site
Orlando, Florida, United States, 32806
United States, Georgia
GSK Investigational Site
Decatur, Georgia, United States, 30030
GSK Investigational Site
Savannah, Georgia, United States, 31405
United States, Minnesota
GSK Investigational Site
Minneapolis, Minnesota, United States, 55415
United States, Missouri
GSK Investigational Site
Saint Louis, Missouri, United States, 63108
United States, North Carolina
GSK Investigational Site
Huntersville, North Carolina, United States, 28078
United States, Pennsylvania
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19107
United States, Texas
GSK Investigational Site
Austin, Texas, United States, 78705
GSK Investigational Site
Bellaire, Texas, United States, 77401
GSK Investigational Site
Dallas, Texas, United States, 75246

Sponsors and Collaborators

ViiV Healthcare

Investigators

Study Director: GSK Clinical Trials ViiV Healthcare
More Information

More Information


Responsible Party: ViiV Healthcare  
ClinicalTrials.gov Identifier: NCT03945981   History of Changes  
Other Study ID Numbers: 212355  
Study First Received: May 8, 2019  
Last Updated: May 5, 2020  
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  

Keywords provided by ViiV Healthcare:

GSK3515864, dolutegravir, Dovato, lamivudine, 3TC, HIV-1, Test and Treat

Additional relevant MeSH terms:
HIV Infections
Lamivudine
Dolutegravir

ClinicalTrials.gov processed this data on August 13, 2020
This information is provided by ClinicalTrials.gov.