An Efficacy, Safety, and Tolerability Study Comparing Dolutegravir Plus Lamivudine With Dolutegravir Plus Tenofovir/Emtricitabine in Treatment naïve HIV Infected Subjects (Gemini 1)

NCT02831673 | Completed Phase 3 Results DMC

• 2 other identifiers: 2048612015-004418-95
• Study Type: interventional
• Target: 719
• Locations: 18 countries
• Sites: 90

Brief 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 \[TDF\]/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 plus 3TC regimen to that of DTG plus 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.

Conditions

Infection, Human Immunodeficiency Virus; HIV Infections

Keywords

safety; treatment naïve; HIV 1; dolutegravir plus lamivudine; non inferiority; tolerability; dolutegravir plus tenofovir/emtricitabine; efficacy

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/mL (c/mL) at Week 48

  Percentage of participants with HIV-1 RNA\<50 c/mL was obtained using Food and Drug Administration (FDA) Snapshot algorithm. The Snapshot algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as non-responders, as well as participants who switch their concomitant antiretroviral therapy (ART) prior to the visit of interest. This endpoint was analyzed using a stratified analysis with Cochran-Mantel-Haenszel (CMH) weights. Intent-To-Treat Exposed (ITT-E) Population was used which comprised of all randomized participants who received at least one dose of study treatment. Percentage values are rounded to the nearest whole digit.

  Week 48

Secondary Outcomes (63)

• Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 24

  Week 24

• Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 96

  Week 96

• Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 144

  Week 144

• Time to Viral Suppression (HIV-1 RNA <50 c/mL) up to Week 144

  Up to Week 144

• CD4+ Cell Counts at Weeks 24 and 48

  Weeks 24 and 48

Study Arms (2)

DTG + 3TC (50 mg+300 mg)

EXPERIMENTAL

Eligible participants will receive one 50 mg tablet of DTG plus one overencapsulated 300 mg 3TC tablet orally once daily upto 96 weeks; thereafter will receive DTG plus 3TC tablet upto Week 148 and will continue to receive this schedule until (i) DTG and 3TC are both locally approved for use as part of a dual regimen, and the single entities of DTG and 3TC are available to patients (e.g. through public health services), or (ii) the DTG/3TC FDC tablet, if required by local regulations, is available, , or (iii) the participant no longer derives clinical benefit, or (iv) the participant meets a protocol defined reason for discontinuation, or (v) development of the DTG plus 3TC dual regimen is terminated.

Drug: Dolutegravir (DTG); Drug: Lamivudine (3TC)

DTG + TDF/FTC FDC (50 mg+300/200 mg)

ACTIVE COMPARATOR

Eligible participants will receive one 50 mg tablet of DTG plus one overencapsulated TDF/ FTC FDC (300/200 mg) tablet orally once daily upto 96 weeks; thereafter will receive DTG plus TDF/FTC FDC tablets upto Week 148 (open-label randomised phase).

Drug: Dolutegravir (DTG); Drug: Tenofovir disoproxil fumarate/Emtricitabine (TDF/FTC FDC)

Interventions

Dolutegravir (DTG) DRUG

DTG is available as 50 mg white, round, biconvex, film coated tablet debossed on one side with 'SV 572' and on the other side with '50'. The tablets are packaged into high density polyethylene (HDPE) bottles with induction seals and child resistant closures. Each 45 ml bottle contains 30 tablets and a desiccant. DTG 50 mg tablet will be orally administered once daily with or without food upto 148 weeks.

DTG + 3TC (50 mg+300 mg); DTG + TDF/FTC FDC (50 mg+300/200 mg)

Lamivudine (3TC) DRUG

Lamivudine is available as swedish orange, 'AA' sized elongated double blind HPMC capsules containing 300 mg lamivudine to visually match overencapsulated TDF/FTC FDC tablet. The capsules are packaged into HDPE bottles with induction seals and child resistant closures. Each 150 mL bottle contains 30 capsules and a desiccant. Overencapsulated 3TC 300 mg tablet will be orally administered once daily with or without food upto 96 weeks. From Week 96 to Week 148, lamivudine will be dispensed as 300 mg white, diamond shaped, scored, film coated tablets debossed with 'GX CJ7' on both sides, packed in over labelled HDPE bottles with child-resistant closures each containing 30 tablets.

DTG + 3TC (50 mg+300 mg)

Tenofovir disoproxil fumarate/Emtricitabine (TDF/FTC FDC) DRUG

Tenofovir disoproxil fumarate and Emtricitabine are available as swedish orange, 'AA' sized elongated double blind HPMC capsules containing 300 mg TDF and 200 mg FTC to visually match overencapsulated 3TC tablet. The capsules are packaged into HDPE bottles with induction seals and child resistant closures. Each 150 mL bottle contains 30 capsules and a desiccant. Overencapsulated tenofovir disoproxil fumarate/emtricitabine tablet will be orally administered once daily with or without food upto 96 weeks. From Week 96 to Week 148, tenofovir disoproxil fumarate/emtricitabine will be dispensed as 300/200 mg white, blue, capsule shaped, film coated tablets debossed with 'GILEAD' on one side and '701' on another side, packed in overlabelled HDPE bottles with polypropylene childresistant closures each containing 30 tablets and a desiccant.

DTG + TDF/FTC FDC (50 mg+300/200 mg)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Participants 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
• Participant 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

You may not qualify if:

• 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 B 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
• 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

Sponsors & Collaborators

• ViiV Healthcare: lead
• PPD Development, LP: collaborator
• GlaxoSmithKline: collaborator

Study Sites (90)

GSK Investigational Site

Phoenix, Arizona, 85015, United States

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GSK Investigational Site

Washington D.C., District of Columbia, 20037, United States

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GSK Investigational Site

Ft. Pierce, Florida, 34982, United States

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GSK Investigational Site

Orlando, Florida, 32806, United States

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West Palm Beach, Florida, 33407, United States

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Decatur, Georgia, 30033, United States

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Indianapolis, Indiana, 46202, United States

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GSK Investigational Site

Springfield, Massachusetts, 01199, United States

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GSK Investigational Site

Berkley, Michigan, 48072, United States

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GSK Investigational Site

Kansas City, Missouri, 64111, United States

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GSK Investigational Site

St Louis, Missouri, 63108, United States

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GSK Investigational Site

Chapel Hill, North Carolina, 27599-7064, United States

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Allentown, Pennsylvania, 18102, United States

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GSK Investigational Site

Providence, Rhode Island, 02906, United States

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GSK Investigational Site

Bellaire, Texas, 77401, United States

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GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, C1181ACH, Argentina

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GSK Investigational Site

Ciudad Autónoma de Buenos Aires, Buenos Aires, C1405CKC, Argentina

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GSK Investigational Site

Buenos Aires, 1141, Argentina

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GSK Investigational Site

Buenos Aires, 1202, Argentina

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Darlinghurst, New South Wales, 2010, Australia

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Sydney, New South Wales, 2010, Australia

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Fortitude Valley, Queensland, 4006, Australia

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GSK Investigational Site

Antwerp, 2000, Belgium

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Brussels, 1000, Belgium

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GSK Investigational Site

Brussels, 1070, Belgium

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GSK Investigational Site

Brussels, 1200, Belgium

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GSK Investigational Site

Ottawa, Ontario, K1H 8L6, Canada

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GSK Investigational Site

Montreal, Quebec, H2L 4E9, Canada

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GSK Investigational Site

Montreal, Quebec, H2L 4P9, Canada

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GSK Investigational Site

Le Kremlin-Bicêtre, 94275, France

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Marseille, 13003, France

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Paris, 75013, France

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GSK Investigational Site

Paris, 75475, France

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GSK Investigational Site

Paris, 75571, France

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Toulouse, 31059, France

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GSK Investigational Site

Munich, Bavaria, 80336, Germany

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GSK Investigational Site

Bonn, North Rhine-Westphalia, 53127, Germany

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GSK Investigational Site

Essen, North Rhine-Westphalia, 45122, Germany

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Berlin, 10439, Germany

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GSK Investigational Site

Hamburg, 20146, Germany

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GSK Investigational Site

Bologna, Emilia-Romagna, 40138, Italy

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GSK Investigational Site

Ferrara, Emilia-Romagna, 44100, Italy

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GSK Investigational Site

Genoa, Liguria, 16132, Italy

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GSK Investigational Site

Brescia, Lombardy, 25123, Italy

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GSK Investigational Site

Busto Arsizio (VA), Lombardy, 21052, Italy

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Milan, Lombardy, 20127, Italy

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GSK Investigational Site

Pavia, Lombardy, 27100, Italy

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Padua, 35128, Italy

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Reggio Emilia, 42121, Italy

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GSK Investigational Site

Roma, 00149, Italy

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GSK Investigational Site

Guadalajara, Jalisco, 44160, Mexico

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GSK Investigational Site

Zapopan, Jalisco, 45170, Mexico

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GSK Investigational Site

Distrito Federal, 06470, Mexico

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Rotterdam, 3015 CE, Netherlands

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Rotterdam, 3079 DZ, Netherlands

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GSK Investigational Site

Coimbra, 3000-075, Portugal

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Lisbon, 1169-050, Portugal

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GSK Investigational Site

Porto, 4369-004, Portugal

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GSK Investigational Site

Cluj-Napoca, 400348, Romania

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GSK Investigational Site

Galati, 800179, Romania

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Moscow, 105275, Russia

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GSK Investigational Site

Oryol, 302040, Russia

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GSK Investigational Site

Saint Petersburg, 196645, Russia

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GSK Investigational Site

Toliyatti, 445846, Russia

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GSK Investigational Site

Yekaterinburg, 620149, Russia

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GSK Investigational Site

Красноярск, 660049, Russia

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GSK Investigational Site

Observatory, Cape Town, 7925, South Africa

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GSK Investigational Site

Busan, 49241, South Korea

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Daegu, 41944, South Korea

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GSK Investigational Site

Seoul, 137-701, South Korea

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GSK Investigational Site

Seoul, 152-703, South Korea

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GSK Investigational Site

Alicante, 03010, Spain

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GSK Investigational Site

Badalona, 08916, Spain

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GSK Investigational Site

Córdoba, 14004, Spain

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GSK Investigational Site

Donostia / San Sebastian, 20080, Spain

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GSK Investigational Site

Elche (Alicante), 03203, Spain

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GSK Investigational Site

Madrid, 28007, Spain

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GSK Investigational Site

Madrid, 28031, Spain

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GSK Investigational Site

Madrid, 28034, Spain

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GSK Investigational Site

Madrid, 28911, Spain

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GSK Investigational Site

Mataró, 08304, Spain

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GSK Investigational Site

Santiago de Compostela, 15706, Spain

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GSK Investigational Site

Valencia, 46014, Spain

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GSK Investigational Site

Vigo, 36312, Spain

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GSK Investigational Site

Kaohsiung City, 824, Taiwan

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GSK Investigational Site

Taipei, 100, Taiwan

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GSK Investigational Site

Taipei, 11217, Taiwan

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GSK Investigational Site

London, SE1 9RT, United Kingdom

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GSK Investigational Site

London, SW10 9NH, United Kingdom

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GSK Investigational Site

Manchester, M8 5RB, United Kingdom

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Related Publications (2)

• Cahn P, Madero JS, Arribas JR, Antinori A, Ortiz R, Clarke AE, Hung CC, Rockstroh JK, Girard PM, Sievers J, Man C, Currie A, Underwood M, Tenorio AR, Pappa K, Wynne B, Fettiplace A, Gartland M, Aboud M, Smith K; GEMINI Study Team. Dolutegravir plus lamivudine versus dolutegravir plus tenofovir disoproxil fumarate and emtricitabine in antiretroviral-naive adults with HIV-1 infection (GEMINI-1 and GEMINI-2): week 48 results from two multicentre, double-blind, randomised, non-inferiority, phase 3 trials. Lancet. 2019 Jan 12;393(10167):143-155. doi: 10.1016/S0140-6736(18)32462-0. Epub 2018 Nov 9.

  PMID: 30420123 BACKGROUND

• Ait-Khaled M, Sierra Madero J, Estrada V, Gulminetti R, Hagins D, Tsai HC, Man C, Sievers J, Grove R, Zolopa A, Wynne B, van Wyk J. Impact of treatment adherence on efficacy of dolutegravir plus lamivudine and dolutegravir plus tenofovir disoproxil fumarate/emtricitabine: pooled analysis of the GEMINI-1 and GEMINI-2 clinical studies. HIV Res Clin Pract. 2021 Dec 9;23(1):9-14. Epub 2021 Dec 16.

  PMID: 34913844 DERIVED

MeSH Terms

Conditions

Infections; Acquired Immunodeficiency Syndrome; HIV Infections

Interventions

dolutegravir; Lamivudine; Tenofovir; Emtricitabine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: GSK Response Center
• Organization: ViiV Healthcare

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  ViiV Healthcare

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2016
• First Posted: July 13, 2016
• Study Start: July 21, 2016
• Primary Completion: March 29, 2018
• Study Completion: August 15, 2022
• Last Updated: August 24, 2023
• Results First Posted: April 18, 2019

Record last verified: 2023-07

Locations

PT (3); BE (4); GB (3); FR (6); TW (3); AR (4); KR (4); US (15); ME (3); ZA (1); AU (3); RU (6); ES (13); DE (5); RO (2); CA (3); NL (2); IT (10)