NCT04021290 - Regimen Switch to Dolutegravir/Lamivudine Fixed Dose Combination From Current Antiretroviral Regimen in HIV-1 Infected and Virologically Suppressed Adults (SALSA) | Crick

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Number of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) >=50 Copies/Milliliter (c/mL) as Per Food and Drug Administration (FDA) Snapshot Category at Week 48

Number of participants with plasma HIV 1 RNA \>=50 c/mL were evaluated using FDA snapshot algorithm at Week 48 to demonstrate the non-inferior antiviral activity of switching to DTG/3TC FDC once daily compared to continuation of CAR over 48 weeks. The FDA snapshot algorithm defines a participant's virologic response status using only the viral load at the predefined time point within a window of time (HIV-RNA equal to or above 50 copies/mL and HIV-RNA below 50 copies/mL ), along with study drug discontinuation status. Participants with plasma HIV 1 RNA \>=50 c/mL were termed as subjects with virologic failure. The third category of the FDA snapshot ("No virologic data") is not pre-defined as an endpoint and therefore not reported separately.

Time frame: Week 48

Secondary Outcomes

Number of Participants With Plasma HIV-1 RNA <50 c/mL Using the FDA Snapshot Algorithm at Week 48

Number of participants with plasma HIV 1 RNA \<50 c/mL were evaluated using FDA snapshot algorithm at Week 48 to demonstrate the antiviral activity of switching to DTG/3TC FDC once daily compared to continuation of CAR over 48 weeks. The FDA snapshot algorithm defines a participant's virologic response status using only the viral load at the predefined time point within a window of time (HIV-RNA equal to or above 50 copies/mL and HIV-RNA below 50 copies/mL ), along with study drug discontinuation status. Participants with plasma HIV 1 RNA \<50 c/mL were termed as subjects with virologic success. The third category of the FDA snapshot ("No virologic data") is not pre-defined as an endpoint and therefore not reported separately.

Time frame: Week 48

Number of Participants With Plasma HIV-1 RNA >=50 c/mL as Per FDA Snapshot Category at Week 24

Number of participants with plasma HIV 1 RNA \>=50 c/mL were evaluated using FDA snapshot algorithm at Week 24 to demonstrate the antiviral activity of switching to DTG/3TC FDC once daily compared to continuation of CAR over 24 weeks. The FDA snapshot algorithm defines a participant's virologic response status using only the viral load at the predefined time point within a window of time (HIV-RNA equal to or above 50 copies/mL and HIV-RNA below 50 copies/mL ), along with study drug discontinuation status. Participants with plasma HIV 1 RNA \>=50 c/mL were termed as subjects with virologic failure. The third category of the FDA snapshot ("No virologic data") is not pre-defined as an endpoint and therefore not reported separately.

Time frame: Week 24

Number of Participants With Plasma HIV-1 RNA <50 c/mL Using the FDA Snapshot Algorithm at Week 24

Number of participants with plasma HIV 1 RNA \<50 c/mL were evaluated using FDA snapshot algorithm at Week 24 to demonstrate the antiviral activity of switching to DTG/3TC FDC once daily compared to continuation of CAR over 24 weeks. The FDA snapshot algorithm defines a participant's virologic response status using only the viral load at the predefined time point within a window of time (HIV-RNA equal to or above 50 copies/mL and HIV-RNA below 50 copies/mL ), along with study drug discontinuation status. Participants with plasma HIV 1 RNA \<50 c/mL were termed as subjects with virologic success. The third category of the FDA snapshot ("No virologic data") is not pre-defined as an endpoint and therefore not reported separately.

Time frame: Week 24

Change From Baseline in Cluster of Differentiation 4 (CD4+) Cell Count for Week 24

CD4+ cells are type of white blood cells that fight infection and as HIV infection progresses, the number of these cells declines. Baseline value is defined as the latest pre-dose assessment with a non-missing value (Day 1). Change from Baseline is defined as post-dose visit value minus Baseline value. Lymphocyte subsets were collected for assessment of this outcome measure by flow cytometry. Change from Baseline in CD4+ lymphocyte count was assessed at Week 24 to evaluate the immune effects of DTG/3TC FDC once daily compared to continuation of CAR. Plasma samples for lymphocyte subsets were collected.

Time frame: Baseline (Day 1) and Week 24

Change From Baseline in CD4+ Cell Count for Week 48

CD4+ cells are type of white blood cells that fight infection and as HIV infection progresses, the number of these cells declines. Baseline value is defined as the latest pre-dose assessment with a non-missing value (Day 1). Change from Baseline is defined as post-dose visit value minus Baseline value. Lymphocyte subsets were collected for assessment of this outcome measure by flow cytometry. Change from Baseline in CD4+ lymphocyte count was assessed at Week 48 to evaluate the immune effects of DTG/3TC FDC once daily compared to continuation of CAR. Plasma samples for lymphocyte subsets were collected.

Time frame: Baseline (Day 1) and Week 48

Change From Baseline in CD4+/ Cluster of Differentiation 8 (CD8+) Cell Counts Ratio for Week 24

CD4+/CD8+ cells are type of white blood cells that fight infection and as HIV infection progresses, the number of these cells declines. Baseline value is defined as the latest pre-dose assessment with a non-missing value (Day 1). Change from Baseline is defined as post-dose visit value minus Baseline value. Lymphocyte subsets were collected for assessment of this outcome measure by flow cytometry. Change from Baseline in CD4+/CD8+ lymphocyte cell count ratio was assessed at Week 24 to evaluate the immune effects of DTG/3TC FDC once daily compared to continuation of CAR. Plasma samples for lymphocyte subsets were collected.

Time frame: Baseline (Day 1) and Week 24

Change From Baseline in CD4+/CD8+ Cell Counts Ratio for Week 48

CD4+/CD8+ cells are type of white blood cells that fight infection and as HIV infection progresses, the number of these cells declines. Baseline value is defined as the latest pre-dose assessment with a non-missing value (Day 1). Change from Baseline is defined as post-dose visit value minus Baseline value. Lymphocyte subsets were collected for assessment of this outcome measure by flow cytometry. Change from Baseline in CD4+/CD8+ lymphocyte cell count ratio was assessed at Week 48 to evaluate the immune effects of DTG/3TC FDC once daily compared to continuation of CAR. Plasma samples for lymphocyte subsets were collected.

Time frame: Baseline (Day 1) and Week 48

Number of Participants With Disease Progression Through Week 24

Participants with disease progression included incidences of HIV-associated conditions, Acquired Immuno Deficiency Syndrome (AIDS) and death. HIV-associated conditions were assessed according to the 2014 HIV infection by Centers for Disease Control and Prevention (CDC) classification system for HIV Infection in adults to evaluate the immune effects of DTG /3TC FDC once daily compared to continuation of CAR.

Time frame: Up to Week 24

Number of Participants With Disease Progression Through Week 48

Participants with disease progression included incidences of HIV-associated conditions, AIDS and death. HIV-associated conditions were assessed according to the 2014 HIV infection by CDC classification system for HIV Infection in adults to evaluate the immune effects of DTG /3TC FDC once daily compared to continuation of CAR.

Time frame: Up to Week 48

Number of Participants With Adverse Events (AEs) and AEs Leading to Discontinuation

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention.

Time frame: Up to Week 52

Number of Participants With AEs by Severity Grades

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs were evaluated by the investigator and graded according to the Division of Acquired Immunodeficiency Syndrome (DAIDS) toxicity scales from Grade 1 to 5 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening, 5=Death). The higher the grade, the more severe the symptoms

Time frame: Up to 52 weeks

Number of Participants With Hepatobiliary Abnormalities Through 52 Weeks

Blood samples were collected to evaluate hepatobiliary abnormalities. Number of participants with Bilirubin (BIL), Alkaline phosphatase (ALP), Alanine Aminotransferase (ALT)/combination of these with levels more than the defined hepatobiliary abnormality criteria were presented. Hepatocellular injury is defined as (\[ALT/ALT ULN\]/\[ALP/ALP ULN\]) \>= 5 and ALT \>=3xULN.

Time frame: Up to Week 52

Number of Participants With Any AEs and AEs by Severity Grades for Those Participants With Baseline Creatinine Clearance of 30-49 mL/Min/1.73m^2

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Number of participants with any AE were presented and AEs were graded according to the DAIDS toxicity scales from Grade 1 to 5 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening, 5=Death). The higher the grade, the more severe the symptoms.

Time frame: Up to 52 weeks

Number of Participants With Any AEs and AEs by Severity Grades for Those Participants With Baseline Creatinine Clearance of >=50 mL/Min/1.73m^2

Time frame: Up to 52 weeks

Number of Participants With Any AEs Leading to Discontinuation Based on Baseline Creatinine Clearance of 30-49 mL/Min/1.73m^2

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention.

Time frame: Up to 52 weeks

Number of Participants With Any AEs Leading to Discontinuation Based on Baseline Creatinine Clearance of >=50 mL/Min/1.73m^2

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention.

Time frame: Up to 52 weeks

Number of Participants With Hepatobiliary Abnormalities Through 52 Weeks Based on Baseline Creatinine Clearance of 30-49 mL/Min/1.73m^2

Time frame: Up to Week 52

Number of Participants With Hepatobiliary Abnormalities Through 52 Weeks Based on Baseline Creatinine Clearance of >=50 mL/Min/1.73m^2

Time frame: Up to Week 52

Change From Baseline in Fasting Lipids at Week 24

Lipid parameters included total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol and triglycerides.

Time frame: Baseline (Day 1) and Week 24

Change From Baseline in Fasting Lipids at Week 48

Lipid parameters included total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides.

Time frame: Baseline (Day 1) and Week 48

Number of Participants With Observed Genotypic and Phenotypic Resistance to Antiretrovirals (ARVs) for Participants Meeting Confirmed Virologic Withdrawal (CVW) Criteria

Genotypic and phenotypic testing was conducted for participants who met the CVW criteria, i.e., one assessment with HIV-1 RNA ≥200 c/mL after Day 1 with an immediately prior HIV-1 RNA ≥50 c/mL at any point in the study.

Time frame: Up to week 48

Change From Baseline in Health Status by HIV Treatment Satisfaction Questionnaire (TSQ) at Week 24

The HIV Treatment Satisfaction Questionnaire (HIVTSQ) is a 10-item self-reported scale that consists of a total score ranging from 0 to 60. Higher scores indicate a greater level of patient-reported satisfaction with their current therapy.

Time frame: Baseline (Day 1) and Week 24

Change From Baseline in Health Status by HIV TSQ at Week 48

The HIVTSQ is a 10-item self-reported scale that consists of a total score ranging from 0 to 60. Higher scores indicate a greater level of patient-reported satisfaction with their current therapy.

Time frame: Baseline (Day 1) and Week 48

Change From Baseline in Health Status by Symptom Distress Module (SDM) at Week 24

SDM is a 20-item self-reported measure that addresses the presence and perceived distress linked to symptoms commonly associated with HIV or its treatment. Each item is rated from 0 to 4 where 0 (complete absence of symptom) and 4 (very bothersome symptom). Overall score calculated as the sum of the scores for each of the 20 items of the questionnaire and ranged from 0 (best health) and 80 (worst health).

Time frame: Baseline (Day 1) and Week 24

Change From Baseline in Health Status by SDM at Week 48

Time frame: Baseline (Day 1) and Week 48

Change From Baseline in Health Status by SDM in Continuation Phase

Time frame: Baseline (Day 1) and Week 76, Week 100, and Week 132

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

Overview

Conditions

Interventions

Eligibility

Locations (119)

Outcomes

Primary Outcomes

Secondary Outcomes