Brief Summary
The study aims at evaluating the maintenance of virologic suppression of dolutegravir/lamivudine (DTG/3TC) fixed dose combination (FDC) at Week 48 post-switch from bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in participants living with Human Immunodeficiency Virus Type 1 (HIV-1) who are of at least 50 years of age and above.
Brief Title
A Study to Evaluate Efficacy, Safety and Tolerability in Antiretroviral Therapy (ART)-Experienced Participants of at Least 50 Years of Age Living With Human Immunodeficiency Virus (HIV) With Virologic Suppression Who Switch to DTG/3TC FDC From BIC/FTC/TAF
Categories
Completion Date
Completion Date Type
Estimated
Conditions
HIV
HIV Infections
Eligibility Criteria
Inclusion Criteria:
* Participants living with HIV-1 with documented plasma HIV-1 RNA \<50 c/mL within 3 months prior to Screening.
* Participants must have been on uninterrupted antiretroviral therapy (ART) for ≥1 year (except for brief periods \[less than 30 days\] where all ART was stopped due to tolerability and/or safety concerns).
* Participants must be on uninterrupted BIC/FTC/TAF for at least 6 months prior to Screening.
* Participants with plasma HIV-1 RNA \<50 c/mL at Screening.
* Participants with no known prior regimen switches due to documented virologic failure (defined as a confirmed plasma HIV 1 RNA ≥200 c/mL).
* Participants with unknown full treatment/clinical history beyond 5 years prior to Screening may be eligible upon discussion and agreement with the medical monitor.
Exclusion Criteria:
* Women participants who are pregnant or breastfeeding or plan to become pregnant or breastfeed during the study.
* Participants with 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/cubic millimetre (mm\^3) are not exclusionary.
* Participants with signs and symptoms which, in the opinion of the Investigator, are suggestive of active severe acute respiratory syndrome-related coronavirus (SARS-CoV-2) infection within 14 days prior to enrolment.
* Participants with severe hepatic impairment (Class C) as determined by Child-Pugh classification.
* 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 antibody (anti-HBs) and HBV deoxyribonucleic acid (DNA) as follows:
1. Participants positive for HBsAg are excluded;
2. Participants negative for anti-HBs but positive for anti-HBc (negative HBsAg status), whether negative or positive for HBV DNA, are excluded;
3. Participants 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.
* Participants with unstable liver disease (as defined by any of the following: presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice or cirrhosis), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment).
* Participants with history of liver cirrhosis with or without hepatitis viral co-infection.
* 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 or intolerance to the study treatment or their components or drugs of their class or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
* 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. Participant's history of suicidal behavior and/or suicidal ideation should be considered when evaluating for suicide risk.
* Participants with any evidence of any major 3TC resistance associated mutations (M184V/I and/or K65R and/or MDR) or presence of any major Integrase strand transfer inhibitor (INSTI) resistance associated mutation in any available prior resistance genotype assay test result. All available historical resistance reports with HIV-1 reverse transcriptase or integrase genotypic data must be provided to ViiV after screening and before enrollment for review by ViiV Virology.
* Participants with any verified Grade 4 laboratory abnormality with the exception of Grade 4 lipid abnormalities.
* Alanine aminotransferase (ALT) ≥5 times the upper limit of normal (ULN) or ALT ≥3xULN and bilirubin ≥1.5xULN (with greater than \[\>\]35 percentage \[%\] direct bilirubin).
* Participant has estimated creatine clearance \<30 millilitres per minute (mL/min) per 1.73 square meter (m\^2) using the refitted, race-neutral Chronic Kidney Disease Epidemiology Collaboration (CKD-EPIcr_R) method.
* Participants living with HIV-1 with documented plasma HIV-1 RNA \<50 c/mL within 3 months prior to Screening.
* Participants must have been on uninterrupted antiretroviral therapy (ART) for ≥1 year (except for brief periods \[less than 30 days\] where all ART was stopped due to tolerability and/or safety concerns).
* Participants must be on uninterrupted BIC/FTC/TAF for at least 6 months prior to Screening.
* Participants with plasma HIV-1 RNA \<50 c/mL at Screening.
* Participants with no known prior regimen switches due to documented virologic failure (defined as a confirmed plasma HIV 1 RNA ≥200 c/mL).
* Participants with unknown full treatment/clinical history beyond 5 years prior to Screening may be eligible upon discussion and agreement with the medical monitor.
Exclusion Criteria:
* Women participants who are pregnant or breastfeeding or plan to become pregnant or breastfeed during the study.
* Participants with 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/cubic millimetre (mm\^3) are not exclusionary.
* Participants with signs and symptoms which, in the opinion of the Investigator, are suggestive of active severe acute respiratory syndrome-related coronavirus (SARS-CoV-2) infection within 14 days prior to enrolment.
* Participants with severe hepatic impairment (Class C) as determined by Child-Pugh classification.
* 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 antibody (anti-HBs) and HBV deoxyribonucleic acid (DNA) as follows:
1. Participants positive for HBsAg are excluded;
2. Participants negative for anti-HBs but positive for anti-HBc (negative HBsAg status), whether negative or positive for HBV DNA, are excluded;
3. Participants 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.
* Participants with unstable liver disease (as defined by any of the following: presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice or cirrhosis), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment).
* Participants with history of liver cirrhosis with or without hepatitis viral co-infection.
* 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 or intolerance to the study treatment or their components or drugs of their class or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
* 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. Participant's history of suicidal behavior and/or suicidal ideation should be considered when evaluating for suicide risk.
* Participants with any evidence of any major 3TC resistance associated mutations (M184V/I and/or K65R and/or MDR) or presence of any major Integrase strand transfer inhibitor (INSTI) resistance associated mutation in any available prior resistance genotype assay test result. All available historical resistance reports with HIV-1 reverse transcriptase or integrase genotypic data must be provided to ViiV after screening and before enrollment for review by ViiV Virology.
* Participants with any verified Grade 4 laboratory abnormality with the exception of Grade 4 lipid abnormalities.
* Alanine aminotransferase (ALT) ≥5 times the upper limit of normal (ULN) or ALT ≥3xULN and bilirubin ≥1.5xULN (with greater than \[\>\]35 percentage \[%\] direct bilirubin).
* Participant has estimated creatine clearance \<30 millilitres per minute (mL/min) per 1.73 square meter (m\^2) using the refitted, race-neutral Chronic Kidney Disease Epidemiology Collaboration (CKD-EPIcr_R) method.
Inclusion Criteria
Inclusion Criteria:
* Participants living with HIV-1 with documented plasma HIV-1 RNA \<50 c/mL within 3 months prior to Screening.
* Participants must have been on uninterrupted antiretroviral therapy (ART) for ≥1 year (except for brief periods \[less than 30 days\] where all ART was stopped due to tolerability and/or safety concerns).
* Participants must be on uninterrupted BIC/FTC/TAF for at least 6 months prior to Screening.
* Participants with plasma HIV-1 RNA \<50 c/mL at Screening.
* Participants with no known prior regimen switches due to documented virologic failure (defined as a confirmed plasma HIV 1 RNA ≥200 c/mL).
* Participants with unknown full treatment/clinical history beyond 5 years prior to Screening may be eligible upon discussion and agreement with the medical monitor.
* Participants living with HIV-1 with documented plasma HIV-1 RNA \<50 c/mL within 3 months prior to Screening.
* Participants must have been on uninterrupted antiretroviral therapy (ART) for ≥1 year (except for brief periods \[less than 30 days\] where all ART was stopped due to tolerability and/or safety concerns).
* Participants must be on uninterrupted BIC/FTC/TAF for at least 6 months prior to Screening.
* Participants with plasma HIV-1 RNA \<50 c/mL at Screening.
* Participants with no known prior regimen switches due to documented virologic failure (defined as a confirmed plasma HIV 1 RNA ≥200 c/mL).
* Participants with unknown full treatment/clinical history beyond 5 years prior to Screening may be eligible upon discussion and agreement with the medical monitor.
Gender
All
Gender Based
false
Keywords
Human Immunodeficiency Virus (HIV)-1
Dolutegravir
Lamivudine
Bictegravir
Emtricitabine
Tenofovir alafenamide
Dovato
Biktarvy
Switch study
≥ 50 years
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
50 Years
NCT Id
NCT05911360
Org Class
Industry
Org Full Name
ViiV Healthcare
Org Study Id
219516
Overall Status
Active, not recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Phase 3b, Multicenter, Single-arm, Open-label Study Evaluating the Efficacy, Safety, and Tolerability of Switching to DTG/3TC Single Tablet Regimen Administered Once Daily From a Bictegravir/Emtricitabine/Tenofovir Alafenamide Single Tablet Regimen in People Living With HIV of at Least 50 Years of Age Who Are Virologically Suppressed
Primary Outcomes
Outcome Measure
Number of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) Greater Than or Equal to (≥)50 Copies/Millilitre (c/mL) per Snapshot Algorithm at Week 48
Outcome Time Frame
Week 48
Secondary Ids
Secondary Id
2022-503137-66-00
Secondary Outcomes
Outcome Time Frame
Weeks 24 and 96
Outcome Measure
Number of Participants With Plasma HIV-1 RNA ≥50 c/mL per Snapshot Algorithm at 24 and 96 Weeks
Outcome Time Frame
Weeks 24,48, and 96
Outcome Measure
Number of Participants With Plasma HIV-1 RNA Less Than (<)50 c/mL per Snapshot Algorithm at 24, 48 and 96 Weeks
Outcome Time Frame
Weeks 24,48, and 96
Outcome Measure
Absolute Values for Cluster of Differentiation 4 (CD4+) Cells Count at 24, 48 and 96 Weeks
Outcome Time Frame
Baseline (Day 1) and at Weeks 24,48, and 96
Outcome Measure
Change From Baseline in CD4+ Cells Count at 24, 48 and 96 Weeks
Outcome Time Frame
Weeks 24,48, and 96
Outcome Measure
Absolute Values for CD4: Cluster of Differentiation 8 (CD8) Ratio at 24, 48 and 96 Weeks
Outcome Time Frame
Baseline (Day 1) and at Weeks 24,48, and 96
Outcome Measure
Change From Baseline in CD4:CD8 Ratio at 24, 48 and 96 Weeks
Outcome Time Frame
Weeks 24, 48, and 96
Outcome Measure
Number of Participants With Disease Progression Through Weeks 24, 48 and 96
Outcome Time Frame
Up to Week 96
Outcome Measure
Number of Participants who Meet Confirmed Virologic Withdrawn Criterion With Viral Resistance Over Time
Outcome Description
A treatment related AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, and considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician, is associated with liver injury and impaired liver function.
Outcome Time Frame
Up to Week 96
Outcome Measure
Number of Participants With Treatment Related Non-serious Adverse Events, all Serious Adverse Events (SAEs), and AEs Leading to Treatment Discontinuation
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
50
Investigators
Investigator Type
Principal Investigator
Investigator Name
Robert Grossberg
Investigator Email
rgrossbe@montefiore.org
Investigator Phone
718-920-5276