Regimen Switch to Dolutegravir/Lamivudine Fixed Dose Combination From Current Antiretroviral Regimen in HIV-1 Infected and Virologically Suppressed Adults (SALSA)

NCT ID: NCT04021290

Last Updated: 2023-10-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 493 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-11
• Study Completion Date: 2022-09-09

Brief Summary

The aim of this study is to determine if virologically suppressed Human Immunodeficiency Virus (HIV) Type 1 infected adults on a current antiretroviral regimen (CAR) (including 2 nucleoside reverse transcriptase inhibitors [NRTIs] plus a third agent) remain suppressed upon switching to dolutegravir/lamivudine (DTG/3TC) fixed dose combination (FDC). The main objective of the study is to demonstrate the non-inferior antiviral activity of switching to DTG/3TC FDC once daily compared to continuation of CAR over 48 weeks in virologically suppressed adults living with HIV-1. The study will also evaluate information regarding the safety and health related quality of life. The study will include Screening Phase (up to 28 days), a Randomization Phase (up to Week 52) and a Continuation Phase (post Week 52). The Continuation Phase is not applicable for participants in Sweden and Denmark. Approximately 490 participants will be randomized in 1:1 ratio to receive DTG/3TC FDC once daily for up to 52 weeks or continue their CAR for 52 weeks. Participants in the DTG/3TC FDC arm who successfully complete up to 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in Continuation Phase.

Conditions

HIV Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Participants receiving DTG/3TC FDC

Eligible participants will be randomized to receive 50 milligrams (mg)/300 mg DTG/3TC FDC therapy from Day 1 up to 52 weeks. Participants who complete 52 weeks of treatment will have the opportunity to continue receiving DTG/3TC FDC once daily in the continuation phase.

Group Type: EXPERIMENTAL

DTG/3TC FDC

Intervention Type: DRUG

DTG/3TC FDC will be available as white, oval, film-coated tablets at a unit dose strength of 50 mg/300 mg. Participants will take DTG/3TC once daily via oral route.

Participants receiving CAR

Eligible participants will continue to receive CAR from Day 1 up to 52 weeks.

Group Type: ACTIVE_COMPARATOR

CAR

Intervention Type: DRUG

Participants who are randomized to the CAR arm will continue to take the current treatment until Week 52. CAR will include 2 NTRIs plus either an INI, NNRTI, or boosted PI or atazanavir unboosted.

Interventions

DTG/3TC FDC

DTG/3TC FDC will be available as white, oval, film-coated tablets at a unit dose strength of 50 mg/300 mg. Participants will take DTG/3TC once daily via oral route.

Intervention Type: DRUG

CAR

Participants who are randomized to the CAR arm will continue to take the current treatment until Week 52. CAR will include 2 NTRIs plus either an INI, NNRTI, or boosted PI or atazanavir unboosted.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Eligible participants must be able to understand and comply with protocol requirements, instructions, and restrictions; participant must be likely to complete the study as planned; participants should be considered appropriate candidates for participation in an investigative clinical trial with oral medication (example given [e.g.] no active problematic substance abuse, acute major organ disease, or potential long-term work assignments out of the country).
• Participant should be aged 18 years or older (or older, if required by local regulatory agencies), at the time of signing the informed consent.
• Participants living with HIV.
• Documented evidence of at least two plasma HIV-1 RNA measurements <50 c/mL in the 12 months prior to Screening: one within the 6 to 12 month window, and one within 6 months prior to Screening.
• Plasma HIV-1 RNA <50 c/mL at Screening.
• Participant must be on uninterrupted current regimen (either the initial or second Combination antiretroviral therapy [cART] regimen) for at least 3 months prior to Screening.

i) Any prior switch, defined as a change of a single drug or multiple drugs simultaneously, must have occurred due to tolerability and/or safety concerns or access to medications, or convenience/simplification and must not have been done for suspected or established treatment failure. The following switches, if they are the only switches, would not be considered a change in regimen. a) A switch from a PI boosted with ritonavir (RTV) to the same PI boosted with cobicistat is allowed (and vice versa). b) A switch from 3TC to emtricitabine (FTC) (and vice versa). c) A switch from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) (and vice versa).

ii) Acceptable stable cART regimens prior to Screening include 2 NRTIs plus a) INI (either the initial or second cART regimen) b) NNRTI (either the initial or second cART regimen) c) Boosted PI (or atazanavir [ATV] unboosted) (either the initial or second PI-based cART regimen).

• A male or female participant.
• A female participant is eligible to participate if she is not pregnant [as confirmed by a negative serum human chorionic gonadotrophin (hCG) test at screen and a negative urine hCG test at randomization (a local serum hCG test at randomization is allowed if it can be done, and results obtained, within 24 hours prior to randomization)], not breastfeeding, and at least one of the following conditions applies; not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow the contraceptive guidance during the treatment period from 28 days prior to the first dose of study medication and for at least 2 weeks after the last dose of study medication. All participants in the study should be counseled on safer sexual practices including the use and benefit/risk of effective barrier methods (e.g., male condom) and on the risk of HIV transmission to an uninfected partner; The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
• Participant must be capable of giving signed informed consent.
• Participants enrolled in France must be affiliated to, or a beneficiary of, a social security category.

Exclusion Criteria

• Women who are pregnant or 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 except cutaneous Kaposi's sarcoma not requiring systemic therapy. Historical or current CD4 cell counts less than 200 cells per cubic millimeter (mm^3) are not exclusionary.
• Participants with severe hepatic impairment (Class C) as determined by Child-Pugh classification.
• Participants with 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 the evidence of Hepatitis B virus (HBV) infection based on the results of testing at Screening for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (anti-HBc), Hepatitis B surface antigen antibody (anti-HBs) and HBV deoxyribonucleic acid (DNA) as follows: Participants positive for HBsAg are excluded; Participants negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and positive for HBV DNA are excluded. Participant's positive for anti-HBc (negative HBsAg status) and positive for anti-HBs (past and/or current evidence) are immune to HBV and are not excluded. Anti-HBc must be either total anti-HBc or anti-HBc immunoglobulin G (IgG), and not anti-HBc Immunoglobulin M (IgM). Participants with a documented history of chronic HBV and current undetectable HBV DNA while on a TAF/TDF regimen are excluded.
• Participants with anticipated need for any hepatitis C virus (HCV) therapy during the randomized phase of the study, or anticipated need for HCV therapy with a potential for adverse drug-drug interactions with DTG or 3TC.
• Participants with untreated syphilis infection (positive rapid plasma reagin [RPR] at Screening without clear documentation of treatment). Participants who are at least 7 days post completed treatment are eligible.
• Participants with history or presence of allergy intolerance to the study interventions or their components or drugs of their class.
• Participants with 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.
• 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.
• Any condition which, in the opinion of the Investigator, may interfere with the absorption, distribution, metabolism or excretion of the study interventions or render the participant unable to take oral medication.
• Use of any regimen consisting of single or dual ART (peri-partum treatment with single dose nevirapine is allowed).
• Participants with current use of stavudine, didanosine, or nelfinavir.
• Participants receiving any prohibited medication and who are unwilling or unable to switch to an alternate medication.
• Participants receiving treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening.
• Participants receiving treatment with any of the following agents within 28 days of Screening like radiation therapy; cytotoxic chemotherapeutic agents; any systemic immune suppressant.
• Participants with 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 investigational product (IP).
• Any evidence of major NRTI mutation or presence of any DTG resistance-associated mutation in any available prior resistance genotype assay test result, if known.
• Participants with any verified Grade 4 laboratory abnormality, with the exception of Grade 4 lipid abnormalities. A single repeat test is allowed during the Screening period to verify a result.
• Participants with alanine aminotransferase (ALT) >= 5 times the upper limit of normal (ULN) or ALT >= 3 times ULN and bilirubin >= 1.5 times ULN (with >35 percent direct bilirubin).
• Participants with creatinine clearance of <30 mL/min/1.73m^2 via Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) method. Participants with creatinine clearance between 30 to 49 mL/min/1.73 m^2 are eligible after the medical monitor has provided approval after reviewing participant's current ART regimen.
• Participants with any acute laboratory abnormality at Screening, which, in the opinion of the investigator, would preclude the participant'sparticipation in the study of an investigational compound.
• Participants within the 12 month window prior to Screening and after confirmed suppression to <50 c/mL, any plasma HIV-1 RNA measurement >200 c/mL.
• Participants within the 12 month window prior to Screening and after confirmed suppression to <50 c/mL, 2 or more consecutive plasma HIV-1 RNA measurements >=50 c/mL. A single plasma HIV-1 RNA measurement >50 c/mL but less than 200 c/mL, with confirmation of return to <50 c/mL is allowed.
• Any history of switch to another regimen, defined as change of a single drug or multiple drugs simultaneously, due to virologic failure to therapy (defined as a confirmed plasma HIV-1 RNA >=400 c/mL).
• Participants with any drug holiday during the 6 months prior to Screening, except for brief periods (less than 1 month) where all ART was stopped due to tolerability and/or safety concerns.
• Participants who are currently participating in or anticipate to be selected for any other interventional study after randomization.
• Participants enrolled in France (or in other countries as required by local regulations or Ethics Committee/Institutional Review Board [IRB]) who participated in any study using an investigational drug or vaccine 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 participate simultaneously in another clinical study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

PPD Development, LP

INDUSTRY

Sponsor Role: collaborator

ViiV Healthcare

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

ViiV Healthcare

Locations

GSK Investigational Site

Los Angeles, California, United States

GSK Investigational Site

Newport Beach, California, United States

GSK Investigational Site

San Francisco, California, United States

GSK Investigational Site

New Haven, Connecticut, United States

GSK Investigational Site

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

GSK Investigational Site

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

GSK Investigational Site

Pensacola, Florida, United States

GSK Investigational Site

West Palm Beach, Florida, United States

GSK Investigational Site

Atlanta, Georgia, United States

GSK Investigational Site

Savannah, Georgia, United States

GSK Investigational Site

Kansas City, Kansas, United States

GSK Investigational Site

St Louis, Missouri, United States

GSK Investigational Site

Hillsborough, New Jersey, United States

GSK Investigational Site

Tulsa, Oklahoma, United States

GSK Investigational Site

Morgantown, West Virginia, United States

GSK Investigational Site

Milwaukee, Wisconsin, United States

GSK Investigational Site

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

GSK Investigational Site

Ciudad de Buenos Aires, Buenos Aires, Argentina

GSK Investigational Site

Rosario, Santa Fe Province, Argentina

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Antwerp, , Belgium

GSK Investigational Site

Brussels, , Belgium

GSK Investigational Site

Ghent, , Belgium

GSK Investigational Site

Salvador, Estado de Bahia, Brazil

GSK Investigational Site

Curitiba, Paraná, Brazil

GSK Investigational Site

Campinas, São Paulo, Brazil

GSK Investigational Site

Manaus, , Brazil

GSK Investigational Site

Rio de Janeiro, , Brazil

GSK Investigational Site

São Paulo, , Brazil

GSK Investigational Site

São Paulo, , Brazil

GSK Investigational Site

Vancouver, British Columbia, Canada

GSK Investigational Site

Winnipeg, Manitoba, Canada

GSK Investigational Site

Ottawa, Ontario, Canada

GSK Investigational Site

Toronto, Ontario, Canada

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Regina, Saskatchewan, Canada

GSK Investigational Site

Guangzhou, Guangdong, China

GSK Investigational Site

Beijing, , China

GSK Investigational Site

Beijing, , China

GSK Investigational Site

Chongqing, , China

GSK Investigational Site

Shanghai, , China

GSK Investigational Site

Aarhus, , Denmark

GSK Investigational Site

Copenhagen, , Denmark

GSK Investigational Site

Hvidovre, , Denmark

GSK Investigational Site

Odense C, , Denmark

GSK Investigational Site

Bobigny, , France

GSK Investigational Site

Bordeaux, , France

GSK Investigational Site

Nice, , France

GSK Investigational Site

Orléans, , France

GSK Investigational Site

Paris, , France

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Paris, , France

GSK Investigational Site

Toulouse, , France

GSK Investigational Site

Tourcoing, , France

GSK Investigational Site

Munich, Bavaria, Germany

GSK Investigational Site

München, Bavaria, Germany

GSK Investigational Site

Frankfurt am Main, Hesse, Germany

GSK Investigational Site

Bonn, North Rhine-Westphalia, Germany

GSK Investigational Site

Cologne, North Rhine-Westphalia, Germany

GSK Investigational Site

Cologne, North Rhine-Westphalia, Germany

GSK Investigational Site

Essen, North Rhine-Westphalia, Germany

GSK Investigational Site

Hamburg, , Germany

GSK Investigational Site

Hamburg, , Germany

GSK Investigational Site

München, , Germany

GSK Investigational Site

Modena, Emilia-Romagna, Italy

GSK Investigational Site

Rome, Lazio, Italy

GSK Investigational Site

Rome, Lazio, Italy

GSK Investigational Site

Milan, Lombardy, Italy

GSK Investigational Site

Milan, Lombardy, Italy

GSK Investigational Site

Milan, Lombardy, Italy

GSK Investigational Site

Pavia, Lombardy, Italy

GSK Investigational Site

Bergamo, , Italy

GSK Investigational Site

Brescia, , Italy

GSK Investigational Site

Guadalajara, Jalisco, Mexico

GSK Investigational Site

Guadalajara, Jalisco, Mexico

GSK Investigational Site

Zapopan, Jalisco, Mexico

GSK Investigational Site

Distrito Federal, , Mexico

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Tolyatti, , Russia

GSK Investigational Site

Yekaterinburg, , Russia

GSK Investigational Site

Bloemfontein, , South Africa

GSK Investigational Site

Cape Town, , South Africa

GSK Investigational Site

Observatory, Cape Town, , South Africa

GSK Investigational Site

A Coruña, , Spain

GSK Investigational Site

Badalona, Barcelona, , Spain

GSK Investigational Site

Cadiz, , Spain

GSK Investigational Site

Granada, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

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Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Murcia, , Spain

GSK Investigational Site

Palma de Mallorca, , Spain

GSK Investigational Site

San Sebastián de los Reyes, , Spain

GSK Investigational Site

Santa Cruz de Tenerife, , Spain

GSK Investigational Site

Seville, , Spain

GSK Investigational Site

Valencia, , Spain

GSK Investigational Site

Gothenburg, , Sweden

GSK Investigational Site

Malmo, , Sweden

GSK Investigational Site

Stockholm, , Sweden

GSK Investigational Site

Stockholm, , Sweden

GSK Investigational Site

Kaohsiumg, , Taiwan

GSK Investigational Site

Kaohsiung City, , Taiwan

GSK Investigational Site

New Taipei City, , Taiwan

GSK Investigational Site

Taichung, , Taiwan

GSK Investigational Site

Taipei, , Taiwan

GSK Investigational Site

Taoyuan District, , Taiwan

GSK Investigational Site

Leeds, Yorkshire, United Kingdom

GSK Investigational Site

Birmingham, , United Kingdom

GSK Investigational Site

Brighton, , United Kingdom

GSK Investigational Site

Bristol, , United Kingdom

GSK Investigational Site

Liverpool, , United Kingdom

GSK Investigational Site

London, , United Kingdom

GSK Investigational Site

London, , United Kingdom

GSK Investigational Site

Manchester, , United Kingdom

GSK Investigational Site

Manchester, , United Kingdom

GSK Investigational Site

Newcastle upon Tyne, , United Kingdom

GSK Investigational Site

Sheffield, , United Kingdom

Countries

United States; Argentina; Belgium; Brazil; Canada; China; Denmark; France; Germany; Italy; Mexico; Russia; South Africa; Spain; Sweden; Taiwan; United Kingdom

References

Llibre JM, Brites C, Cheng CY, Osiyemi O, Galera C, Hocqueloux L, Maggiolo F, Degen O, Taylor S, Blair E, Man C, Wynne B, Oyee J, Underwood M, Curtis L, Bontempo G, van Wyk J. Efficacy and Safety of Switching to the 2-Drug Regimen Dolutegravir/Lamivudine Versus Continuing a 3- or 4-Drug Regimen for Maintaining Virologic Suppression in Adults Living With Human Immunodeficiency Virus 1 (HIV-1): Week 48 Results From the Phase 3, Noninferiority SALSA Randomized Trial. Clin Infect Dis. 2023 Feb 18;76(4):720-729. doi: 10.1093/cid/ciac130.

Reference Type: BACKGROUND

PMID: 35235656 (View on PubMed)

Kumar P, Clarke AE, Jonsson-Oldenbuttel C, Deltoro MG, Di Giambenedetto S, Brites C, Hocqueloux L, Lu PL, Oyee J, Oglesby A, Wynne B, Jones B, Evitt LA, Fox D, Kisare M, Priest J. Patient-Reported Outcomes After Switching to a 2-Drug Regimen of Fixed-Dose Combination Dolutegravir/Lamivudine: 48-Week Results from the SALSA Study. AIDS Behav. 2025 Jan;29(1):235-245. doi: 10.1007/s10461-024-04479-9. Epub 2024 Sep 3.

Reference Type: DERIVED

PMID: 39225890 (View on PubMed)

Scholten S, Cahn P, Portilla J, Bisshop F, Hodder S, Ruane P, Kaplan R, Wynne BR, Man CY, Grove R, Wang R, Jones B, Ait-Khaled M, Kisare M, Okoli C. Dolutegravir/Lamivudine Efficacy and Safety Outcomes in People With HIV-1 With or Without Historical Resistance Results at Screening: 48-Week Pooled Analysis. Open Forum Infect Dis. 2024 Jul 1;11(7):ofae365. doi: 10.1093/ofid/ofae365. eCollection 2024 Jul.

Reference Type: DERIVED

PMID: 39015350 (View on PubMed)

Walmsley S, Smith DE, Gorgolas M, Cahn PE, Lutz T, Lacombe K, Kumar PN, Wynne B, Grove R, Bontempo G, Moodley R, Okoli C, Kisare M, Jones B, Clark A, Ait-Khaled M. Efficacy and safety of switching to dolutegravir/lamivudine in virologically suppressed people with HIV-1 aged >/= 50 years: week 48 pooled results from the TANGO and SALSA studies. AIDS Res Ther. 2024 Mar 21;21(1):17. doi: 10.1186/s12981-024-00604-9.

Reference Type: DERIVED

PMID: 38515183 (View on PubMed)

Masters MC, Cohn SE. Two-drug HIV regimens: more data still needed. Lancet HIV. 2021 Aug;8(8):e454-e455. doi: 10.1016/S2352-3018(21)00106-5. No abstract available.

Reference Type: DERIVED

PMID: 34358493 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

208090

Identifier Type: -

Identifier Source: org_study_id