An Efficacy, Safety, and Tolerability Study Comparing Dolutegravir (DTG) Plus Lamivudine (3TC) With Dolutegravir Plus Tenofovir/Emtricitabine in Treatment naïve HIV Infected Participants (Gemini 2)

Last updated: December 4, 2023
Sponsor: ViiV Healthcare
Overall Status: Completed

Phase

3

Condition

Hiv Infections

Hiv/aids

Aids And Aids Related Infections

Treatment

Lamivudine (3TC)

Tenofovir disoproxil fumarate/Emtricitabine (TDF/FTC FDC)

Dolutegravir (DTG)

Clinical Study ID

NCT02831764
205543
2016-000459-28
  • Ages > 18
  • All Genders

Study Summary

This study will compare safety, efficacy, and tolerability of a two drug regimen of dolutegravir (DTG) plus (+) lamivudine (3TC) administered once daily with DTG plus two nucleoside reverse transcriptase inhibitors (tenofovir disoproxil fumarate [TDF]/emtricitabine [FTC] fixed dose combination [FDC]) administered once daily in human immunodeficiency virus (HIV) 1 infected adult participants that have not previously received antiretroviral therapy. The study is designed to demonstrate the non inferior antiviral activity of DTG + 3TC regimen to that of DTG + TDF/FTC FDC and will characterise the long term antiviral activity, tolerability and safety of DTG plus 3TC through Week 148. Approximately, 700 participants will be randomised 1:1 to receive DTG + 3TC or DTG + TDF/FTC FDC. Participants will be stratified by screening HIV 1 ribonucleotide nucleic acid (RNA) levels and by screening CD4+ (cluster of differentiation 4) cell count.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Must be an HIV 1 infected adult >=18 years of age (or older, if required by local regulations) at the time of signing the informed consent

  • An eligible female participant should not be pregnant (as confirmed by a negative serum human chorionic gonadotrophin (hCG) test at Screening and negative urine test at Baseline), not lactating, and at least one of the following conditions applies

  • Non reproductive premenopausal women are those that have undergone documented tubal ligation or documented hysteroscopic tubal occlusion procedure with follow up confirmation of bilateral tubal occlusion or documented bilateral oophorectomy or hysterectomy

  • Non reproductive premenopausal women are those with 12 months of spontaneous amenorrhea and >=45 years of age

  • Women with reproductive potential agree to follow one of the protocol-defined methods for avoiding pregnancy

  • Should have screening plasma HIV 1 RNA levels of 1000 c/mL to <=100,000 c/mL. If an independent review of accumulated data from other clinical trials investigating the DTG plus 3TC dual regimen is supportive of the DTG plus 3TC treatment regimen, enrolment will be opened to participants with Screening plasma HIV 1 RNA of 1000 c/mL to <=500,000 c/mL

  • Participant should be antiretroviral naïve (defined as <=10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV 1 infection). 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 >1 year from HIV diagnosis or there is documented HIV seronegativity between the last prophylactic dose and the date of HIV diagnosis

  • Participants or the participants legal representative capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and the protocol

  • Participants enrolled in France: a participant will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category

Exclusion Criteria

  • Women who are breastfeeding or plan to become pregnant or breastfeed during the study

  • Any evidence of an active centers for disease control and prevention (CDC) Stage 3 disease (CDC, 2014), except cutaneous Kaposi's sarcoma not requiring systemic therapy and historical or current CD4 cell counts less than 200 cells/mm^3

  • Participants with severe hepatic impairment (Class C) as determined by Child Pugh classification

  • Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones

  • Evidence of hepatitis B virus (HBV) infection or HBV surface antibody (anti-HBs or HBsAb) based on:

Participants positive for HBV surface antigen (HBsAg) at screening will be excluded Participants negative for HBV core antibody (anti HBs) but positive for anti HBc (negative HBsAg status) and positive for HBV deoxyribose nucleic acid (DNA) will be excluded; however, participants positive for anti HBc (negative HBsAg status) and positive for anti HBs (past and/or current evidence) are immune to HBV and will not be excluded

  • Anticipated need for any hepatitis C virus (HCV) therapy during the first 48 weeks of the study and for HCV therapy based on interferon or any drugs that have a potential for adverse drug:drug interactions with study treatment throughout the entire study period

  • Untreated syphilis infection positive RPR at Screening without clear documentation of treatment. Participants who are at least 14 days post completed treatment are eligible

  • History or presence of allergy or intolerance to the study drugs or their components or drugs of their class

  • Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non invasive cutaneous squamous cell carcinoma, or cervical, anal or penile intraepithelial neoplasia; other localised 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. Recent history of suicidal behaviour and/or suicidal ideation may be considered as evidence of serious suicide risk

  • Treatment with an HIV 1 immunotherapeutic vaccine within 90 days of Screening

  • Treatment with any of the following agents within 28 days of Screening:

  • Radiation therapy,

  • Cytotoxic chemotherapeutic agents,

  • Any systemic immune suppressant

  • Treatment with any agent, except recognised ART as allowed above, with documented activity against HIV 1 in vitro within 28 days of first dose of study treatment

  • 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

  • Participants enrolled in France: the participant has participated in any study using an investigational drug during the previous 60 days or 5 half lives, or twice the duration of the biological effect of the experimental drug or vaccine, whichever is longer, prior to screening for the study or the participant will participate simultaneously in another clinical study

  • Any evidence of pre existing viral resistance based on the presence of any major resistance associated mutation in the Screening result or, if known, in any historical resistance test result

  • Any verified Grade 4 laboratory abnormality. A single repeat test is allowed during the Screening period to verify a result

  • Any acute laboratory abnormality at Screening, which, in the opinion of the Investigator, would preclude the participants participation in the study of an investigational compound

  • Alanine aminotransferase (ALT) >=5 times the upper limit of normal (ULN) or ALT >=3xULN and bilirubin >=1.5xULN (with >35% direct bilirubin)

  • Creatinine clearance of <50 mL/min per 1.73 m^2 via the chronic kidney disease epidemiology collaboration (CKD EPI) method

Study Design

Total Participants: 722
Treatment Group(s): 3
Primary Treatment: Lamivudine (3TC)
Phase: 3
Study Start date:
July 18, 2016
Estimated Completion Date:
June 29, 2022

Connect with a study center

  • GSK Investigational Site

    Rosario, Santa Fe S2000PBJ
    Argentina

    Site Not Available

  • GSK Investigational Site

    Buenos Aires, C1425 AWK
    Argentina

    Site Not Available

  • GSK Investigational Site

    Ciudad Autónoma de Buenos Aires, C1426ABP
    Argentina

    Site Not Available

  • GSK Investigational Site

    Cordoba, 5000
    Argentina

    Site Not Available

  • GSK Investigational Site

    San Isidro, B1642BZA
    Argentina

    Site Not Available

  • GSK Investigational Site

    Darlinghurst, New South Wales 2010
    Australia

    Site Not Available

  • GSK Investigational Site

    Parramatta, New South Wales 2150
    Australia

    Site Not Available

  • GSK Investigational Site

    Melbourne, Victoria Prahran 3181
    Australia

    Site Not Available

  • GSK Investigational Site

    North Fitzroy, Victoria 3068
    Australia

    Site Not Available

  • GSK Investigational Site

    Prahran, Victoria 3181
    Australia

    Site Not Available

  • GSK Investigational Site

    Bruxelles, 1090
    Belgium

    Site Not Available

  • GSK Investigational Site

    Gent, 9000
    Belgium

    Site Not Available

  • GSK Investigational Site

    Lodelinsart, 6042
    Belgium

    Site Not Available

  • GSK Investigational Site

    Vancouver, British Columbia V6Z 2C7
    Canada

    Site Not Available

  • GSK Investigational Site

    Toronto, Ontario M5G 2N2
    Canada

    Site Not Available

  • GSK Investigational Site

    Montreal, Quebec H4A 3J1
    Canada

    Site Not Available

  • GSK Investigational Site

    Bobigny, 93009
    France

    Site Not Available

  • GSK Investigational Site

    Lyon, 69317
    France

    Site Not Available

  • GSK Investigational Site

    Montpellier Cedex 5, 34295
    France

    Site Not Available

  • GSK Investigational Site

    Paris, 75020
    France

    Site Not Available

  • GSK Investigational Site

    Paris Cedex 20, 75970
    France

    Site Not Available

  • GSK Investigational Site

    Frankfurt am Main, Hessen 60590
    Germany

    Site Not Available

  • GSK Investigational Site

    Bonn, Nordrhein-Westfalen 53127
    Germany

    Site Not Available

  • GSK Investigational Site

    Koeln, Nordrhein-Westfalen 50937
    Germany

    Site Not Available

  • GSK Investigational Site

    Frankfurt/main, 60590
    Germany

    Site Not Available

  • GSK Investigational Site

    Hamburg, 20099
    Germany

    Site Not Available

  • GSK Investigational Site

    München, 81675
    Germany

    Site Not Available

  • GSK Investigational Site

    Modena, Emilia-Romagna 41100
    Italy

    Site Not Available

  • GSK Investigational Site

    Genova, Liguria 16128
    Italy

    Site Not Available

  • GSK Investigational Site

    Milano, Lombardia 20157
    Italy

    Site Not Available

  • GSK Investigational Site

    Torino, Piemonte 10149
    Italy

    Site Not Available

  • GSK Investigational Site

    Bergamo, 24128
    Italy

    Site Not Available

  • GSK Investigational Site

    Monza, 20900
    Italy

    Site Not Available

  • GSK Investigational Site

    Guadalajara, Jalisco 44280
    Mexico

    Site Not Available

  • GSK Investigational Site

    Distrito Federal, 03720
    Mexico

    Site Not Available

  • GSK Investigational Site

    Mexico, 14000
    Mexico

    Site Not Available

  • GSK Investigational Site

    Callao, Callao 02
    Peru

    Site Not Available

  • GSK Investigational Site

    Lima, Callao 2
    Peru

    Site Not Available

  • GSK Investigational Site

    Bydgoszcz, 85-030
    Poland

    Site Not Available

  • GSK Investigational Site

    Amadora, 2720-276
    Portugal

    Site Not Available

  • GSK Investigational Site

    Lisboa, 1349-019
    Portugal

    Site Not Available

  • GSK Investigational Site

    Porto, 4200-319
    Portugal

    Site Not Available

  • GSK Investigational Site

    Bucharest, 021105
    Romania

    Site Not Available

  • GSK Investigational Site

    Bucuresti, 30303
    Romania

    Site Not Available

  • GSK Investigational Site

    Iasi, 700116
    Romania

    Site Not Available

  • GSK Investigational Site

    Izhevsk, 426067
    Russian Federation

    Site Not Available

  • GSK Investigational Site

    Kazan, 420061
    Russian Federation

    Site Not Available

  • GSK Investigational Site

    Kemerovo, 650056
    Russian Federation

    Site Not Available

  • GSK Investigational Site

    Krasnodar, 350015
    Russian Federation

    Site Not Available

  • GSK Investigational Site

    St. Petersburg, 193167
    Russian Federation

    Site Not Available

  • GSK Investigational Site

    St.Peterburg, 190103
    Russian Federation

    Site Not Available

  • GSK Investigational Site

    Alcorcon, 28922
    Spain

    Site Not Available

  • GSK Investigational Site

    Barcelona, 08036
    Spain

    Site Not Available

  • GSK Investigational Site

    Granada, 18014
    Spain

    Site Not Available

  • GSK Investigational Site

    Madrid, 28046
    Spain

    Site Not Available

  • GSK Investigational Site

    Malaga, 29010
    Spain

    Site Not Available

  • GSK Investigational Site

    Marid, 28040
    Spain

    Site Not Available

  • GSK Investigational Site

    Sevilla, 41013
    Spain

    Site Not Available

  • GSK Investigational Site

    Valencia, 46026
    Spain

    Site Not Available

  • GSK Investigational Site

    Bern, 3010
    Switzerland

    Site Not Available

  • GSK Investigational Site

    Geneve, CH-1205
    Switzerland

    Site Not Available

  • GSK Investigational Site

    Zuerich, 8091
    Switzerland

    Site Not Available

  • GSK Investigational Site

    Kaohsiung, 813
    Taiwan

    Site Not Available

  • GSK Investigational Site

    New Taipei, 220
    Taiwan

    Site Not Available

  • GSK Investigational Site

    Taichung, 40705
    Taiwan

    Site Not Available

  • GSK Investigational Site

    Tainan, 704
    Taiwan

    Site Not Available

  • GSK Investigational Site

    Taipei, 11490
    Taiwan

    Site Not Available

  • GSK Investigational Site

    Taoyuan, 330
    Taiwan

    Site Not Available

  • GSK Investigational Site

    Woolwich, London, London SE18 4QH
    United Kingdom

    Site Not Available

  • GSK Investigational Site

    Brighton, BN2 5BE
    United Kingdom

    Site Not Available

  • GSK Investigational Site

    Liverpool, L69 3GE
    United Kingdom

    Site Not Available

  • GSK Investigational Site

    London, E1 1BB
    United Kingdom

    Site Not Available

  • GSK Investigational Site

    Manchester, M13 0FH
    United Kingdom

    Site Not Available

  • GSK Investigational Site

    Birmingham, Alabama 35294-3300
    United States

    Site Not Available

  • GSK Investigational Site

    Los Angeles, California 90069
    United States

    Site Not Available

  • GSK Investigational Site

    Sacramento, California 95825
    United States

    Site Not Available

  • GSK Investigational Site

    San Francisco, California 94109
    United States

    Site Not Available

  • GSK Investigational Site

    San Leandro, California 94577
    United States

    Site Not Available

  • GSK Investigational Site

    Torrance, California 90502
    United States

    Site Not Available

  • GSK Investigational Site

    Aurora, Colorado 80045
    United States

    Site Not Available

  • GSK Investigational Site

    Washington, District of Columbia 20005
    United States

    Site Not Available

  • GSK Investigational Site

    Washington, D.C., District of Columbia 20005
    United States

    Site Not Available

  • GSK Investigational Site

    Fort Pierce, Florida 34982
    United States

    Site Not Available

  • GSK Investigational Site

    Miami, Florida 33133
    United States

    Site Not Available

  • GSK Investigational Site

    Orlando, Florida 32803
    United States

    Site Not Available

  • GSK Investigational Site

    West Palm Beach, Florida 33407
    United States

    Site Not Available

  • GSK Investigational Site

    Decatur, Georgia 30033
    United States

    Site Not Available

  • GSK Investigational Site

    Savannah, Georgia 31401
    United States

    Site Not Available

  • GSK Investigational Site

    Chicago, Illinois 60612
    United States

    Site Not Available

  • GSK Investigational Site

    Berkeley, Michigan 48072
    United States

    Site Not Available

  • GSK Investigational Site

    Berkley, Michigan 48072
    United States

    Site Not Available

  • GSK Investigational Site

    Saint Louis, Missouri 63139
    United States

    Site Not Available

  • GSK Investigational Site

    St. Louis, Missouri 63139
    United States

    Site Not Available

  • GSK Investigational Site

    Hillsborough, New Jersey 08844
    United States

    Site Not Available

  • GSK Investigational Site

    Newark, New Jersey 07102
    United States

    Site Not Available

  • GSK Investigational Site

    Cincinnati, Ohio 45267-0405
    United States

    Site Not Available

  • GSK Investigational Site

    Austin, Texas 78705
    United States

    Site Not Available

  • GSK Investigational Site

    Dallas, Texas 75246
    United States

    Site Not Available

  • GSK Investigational Site

    Fort Worth, Texas 76104
    United States

    Site Not Available

  • GSK Investigational Site

    Houston, Texas 77009
    United States

    Site Not Available

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