Phase 3
N=743
Switch Study to Evaluate Dolutegravir Plus Lamivudine in Virologically Suppressed Human Immunodeficiency Virus Type 1 Positive Adults (TANGO)
HIV Infections
Bottom Line
View on ClinicalTrials.gov: NCT03446573 ↗Enrolled (actual)
743
Serious AEs
11.9%
Results posted
Jun 2020
Primary outcome: Primary: Percentage of Participants With Virologic Failure Endpoint as Per Food and Drug Administration (FDA) Snapshot Category at Week 48 — 0.3; 0.5 Percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- DTG + 3TC (Drug); TAF based regimen (TBR) (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- ViiV Healthcare
- Primary completion
- May 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Virologic Failure Endpoint as Per Food and Drug Administration (FDA) Snapshot Category at Week 48 |
0.3; 0.5 | — |
| SECONDARY Percentage of Participants With Plasma HIV-1 RNA <50 c/mL as Per Snapshot Algorithm at Week 48 |
93.2; 93.0 | — |
| SECONDARY Percentage of Participants With Virologic Failure Endpoint as Per FDA Snapshot Category at Week 24 |
0.3; 0.8 | — |
| SECONDARY Percentage of Participants With Virologic Failure Endpoint as Per FDA Snapshot Category at Weeks 96, 144 |
0.3; 1.1; 0.3; 1.3 | — |
| SECONDARY Percentage of Participants With Plasma HIV-1 RNA <50 c/mL as Per Snapshot Algorithm at Week 24 |
95; 96 | — |
| SECONDARY Percentage of Participants With Plasma HIV-1 RNA <50 c/mL as Per Snapshot Algorithm at Weeks 96 and 144 |
85.9; 79.0; 85.9; 81.7 | — |
| SECONDARY Change From Baseline in CD4+ Cell Count at Weeks 24 and 48 |
21.0; 6.0; 22.5; 11.0 | — |
| SECONDARY Change From Baseline in CD4+ Cell Count at Weeks 96 and 144 |
61.0; 45.0; 36.0; 35.0 | — |
| SECONDARY Change From Baseline in CD4+/CD8+ Cell Count Ratio at Weeks 24 and 48 |
0.010; 0.040; 0.030; 0.050 | — |
| SECONDARY Change From Baseline in CD4+/CD8+ Cell Count Ratio at Weeks 96 and 144 |
0.035; 0.080; 0.060; 0.100 | — |
| SECONDARY Number of Participants With Disease Progression at Weeks 24 and 48 |
1; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Disease Progression at Weeks 96 and 144 |
2; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Any Serious Adverse Events (SAEs) and Common (>=2%) Non-serious Adverse Events (Non-SAEs): Up to Week 48 |
222; 204; 21; 16 | — |
| SECONDARY Number of Participants Randomized to TBR Arm Receiving TDF-based Regimen With Any SAEs and Common (>=2%) Non-SAEs: Up to Week 48 |
1; 0 | — |
| SECONDARY Number of Participants With Any SAEs and Common (>=2%) Non-SAEs: Up to Week 148 |
307; 304; 57; 44 | — |
| SECONDARY Number of Participants With AEs by Their Severity Grades: Up to Week 48 |
102; 94; 170; 177; 19; 15 | — |
| SECONDARY Number of Participants Randomized to TBR Arm Receiving TDF-based Regimen With AEs by Their Severity Grades: Up to Week 48 |
0; 1; 0; 0; 0 | — |
| SECONDARY Number of Participants With AEs by Their Severity Grades: Up to Week 144 |
57; 65; 217; 208; 50; 54 | — |
| SECONDARY Number of Participants Who Discontinued the Treatment Due to AEs: Up to Week 48 |
13; 2 | — |
| SECONDARY Number of Participants Randomized to TBR Arm Receiving TDF-based Regimen Who Discontinued the Treatment Due to AEs: Up to Week 48 |
— | — |
| SECONDARY Number of Participants Who Discontinued the Treatment Due to AEs: Up to Week 144 |
23; 7 | — |
| SECONDARY Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities: Up to Week 48 |
3; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants Randomized to TBR Arm Receiving TDF-based Regimen With Maximum Post-Baseline Emergent Hematology Toxicities: Up to Week 36 |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities: Up to Week 144 |
7; 2; 1; 2; 0; 0 | — |
| SECONDARY Number of Participants With Maximum Post-Baseline Emergent Clinical Chemistry Toxicities: Up to Week 48 |
24; 18; 6; 4; 1; 1 | — |
| SECONDARY Number of Participants Randomized to TBR Arm Receiving TDF-based Regimen With Maximum Post-Baseline Emergent Clinical Chemistry Toxicities: Up to Week 36 |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Maximum Post-Baseline Emergent Clinical Chemistry Toxicities: Up to Week 144 |
55; 49; 11; 9; 5; 3 | — |
| SECONDARY Change From Baseline in Renal Biomarkers- Urine Albumin/Creatinine (UA/C) Ratio and Urine Protein/Creatinine (UP/C) Ratio at Weeks 24 and 48 |
1.080; 1.022; 1.125; 1.059; 0.955; 0.976 | 0.257 |
| SECONDARY Change From Baseline in Renal Biomarkers- UA/C Ratio and UP/C Ratio at Weeks 24 and 48 in Participants Randomized to TBR Receiving TDF-based Regimen |
0; 0.3 | — |
| SECONDARY Change From Baseline in Renal Biomarkers- UA/C Ratio and UP/C Ratio at Weeks 96 and 144 |
1.058; 1.075; 1.203; 1.200; 1.048; 1.105 | 0.700 |
| SECONDARY Change From Baseline in Renal Biomarkers- Urine Beta-2 Microglobulin/Urine Creatinine Ratio at Weeks 24 and 48 |
0.991; 1.034; 0.973; 0.922 | 0.560 |
| SECONDARY Change From Baseline in Renal Biomarkers- Urine Beta-2 Microglobulin/Urine Creatinine Ratio at Weeks 24 and 48 in Participants Randomized to TBR Arm Receiving TDF-based Regimen |
— | — |
| SECONDARY Change From Baseline in Renal Biomarkers- Urine Beta-2 Microglobulin/Urine Creatinine Ratio at Weeks 96 and 144 |
1.080; 0.986; 0.904; 0.958 | 0.081 |
| SECONDARY Change From Baseline in Renal Biomarkers- Urine Phosphate at Weeks 24 and 48 |
0.955; 0.940; 0.969; 0.970 | 0.758 |
| SECONDARY Change From Baseline in Renal Biomarkers- Urine Phosphate at Weeks 24 and 48 in Participants Randomized to TBR Arm Receiving TDF-based Regimen |
2.9 | — |
| SECONDARY Change From Baseline in Renal Biomarkers- Urine Phosphate at Weeks 96 and 144 |
0.960; 0.978; 0.890; 0.912 | 0.806 |
| SECONDARY Change From Baseline in Renal Biomarkers- Urine Retinol Binding Protein 4/Urine Creatinine at Weeks 24 and 48 |
0.860; 0.920; 1.063; 1.068 | 0.264 |
| SECONDARY Change From Baseline in Renal Biomarkers- Urine Retinol Binding Protein 4/Urine Creatinine at Weeks 24 and 48 in Participants Randomized to TBR Arm Receiving TDF-based Regimen |
1.04 | — |
| SECONDARY Change From Baseline in Renal Biomarkers- Urine Retinol Binding Protein 4/Urine Creatinine at Weeks 96 and 144 |
0.926; 0.851; 1.188; 1.227 | 0.011 sig |
| SECONDARY Change From Baseline in Fasting Lipids at Weeks 24 and 48 |
-0.325; 0.000; -0.200; 0.100; -0.210; -0.060 | — |
| SECONDARY Change From Baseline in Fasting Lipids at Weeks 24 and 48 in Participants Randomized to TBR Arm Receiving TDF-based Regimen |
0; -0.67; 1.36; 0.05 | — |
| SECONDARY Change From Baseline in Fasting Lipids at Weeks 96 and 144 |
-3.7; 1.2; -4.0; 3.8; -5.6; 1.7 | — |
| SECONDARY Number of Participants With Genotypic Resistance: Up to Week 48 |
0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Genotypic Resistance: Up to Week 144 |
0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Phenotypic Resistance: Up to Week 48 |
1; 0; 1; 0; 1; 0 | — |
| SECONDARY Number of Participants With Phenotypic Resistance: Up to Week 144 |
2; 0; 2; 0; 2; 0 | — |
| SECONDARY Change From Baseline in Bone Biomarkers-serum Bone-specific ALP (Bone-ALP), Osteocalcin, Serum Procollagen 1 N-Terminal Propeptide (P1NP) and Serum Type 1 Collagen C-telopeptides (CTX-1) at Weeks 24 and 48 |
-0.77; -1.05; -0.03; -0.34; -1.08; 0.26 | 0.047 sig |
| SECONDARY Change From Baseline in Bone Biomarkers-serum Bone-specific ALP (Bone-ALP), Osteocalcin, Serum P1NP and Serum CTX-1 in Participants Randomized to TBR Arm Receiving TDF-based Regimen at Weeks 24 and 48 |
0.3; 13.4; 11; 0.045 | — |
| SECONDARY Change From Baseline in Bone Biomarkers-serum Bone-ALP, Osteocalcin, Serum P1NP and Serum Type 1 CTX-1 at Weeks 96 and 144 |
-0.62; -0.79; -0.27; -0.40; -1.97; -0.10 | 0.386 |
| SECONDARY Change From Baseline in Bone Biomarker: Serum 25-hydroxyvitamin D at Weeks 24 and 48 |
0.0; 2.1; -5.8; -3.5 | 0.173 |
| SECONDARY Change From Baseline in Bone Biomarker: Serum 25-hydroxyvitamin D at Weeks 24 and 48 in Participants Randomized to TBR Arm Receiving TDF-based Regimen |
2 | — |
| SECONDARY Change From Baseline in Bone Biomarker: Serum 25-hydroxyvitamin D at Weeks 96 and 144 |
-11.5; -2.2; -7.5; -1.9 | <0.001 sig |
| SECONDARY Change From Baseline in Renal Biomarker- Serum Cystatin C at Weeks 24 and 48 |
-0.03; -0.02; 0.00; 0.01 | 0.027 sig |
| SECONDARY Change From Baseline in Renal Biomarker- Serum Cystatin C at Weeks 24 and 48 in Participants Randomized to TBR Arm Receiving TDF-based Regimen |
— | — |
| SECONDARY Change From Baseline in Renal Biomarker- Serum Cystatin C at Weeks 96 and 144 |
0.07; 0.10; 0.13; 0.14 | 0.004 sig |
| SECONDARY Change From Baseline in Renal Biomarker- Serum GFR From Cystatin C Adjusted Using CKD-EPI and Serum GFR From Creatinine Adjusted Using CKD-EPI at Weeks 24 and 48 |
3.2; 1.5; 0.1; -1.6; -8.8; -3.8 | 0.012 sig |
| SECONDARY Change From Baseline in Renal Biomarker- Serum GFR From Cystatin C Adjusted Using CKD-EPI and Serum GFR From Creatinine Adjusted Using CKD-EPI at Weeks 24 and 48 in Participants Randomized to TBR Arm Receiving TDF-based Regimen |
0; 4 | — |
| SECONDARY Change From Baseline in Renal Biomarker- Serum GFR From Cystatin C Adjusted Using CKD-EPI and Serum GFR From Creatinine Adjusted Using CKD-EPI at Weeks 96 and 144 |
-7.6; -11.7; -13.9; -15.8; -7.2; -1.9 | 0.002 sig |
| SECONDARY Change From Baseline in Renal Biomarker- Serum Creatinine at Weeks 24 and 48 |
7.47; 3.11; 6.67; 2.18 | <0.001 sig |
| SECONDARY Change From Baseline in Renal Biomarker- Serum Creatinine at Weeks 24 and 48 in Participants Randomized to TBR Arm Receiving TDF-based Regimen |
-8 | — |
| SECONDARY Change From Baseline in Renal Biomarker- Serum Creatinine at Weeks 96 and 144 |
5.53; 0.58; 9.25; 5.17 | <0.001 sig |
| SECONDARY Change From Baseline in European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Utility Score at Week 24 and 48 |
0.0029; 0.0046; 0.0037; 0.0023 | 0.741 |
| SECONDARY Change From Baseline in EQ-5D-5L Utility Score at Weeks 96 and 144 |
-0.0036; -0.0038; -0.0151; -0.0042 | 0.965 |
| SECONDARY Change From Baseline in EQ-5D-5L Thermometer Scores at Week 24 and 48 |
1.2; 1.3; 1.1; 1.7 | 0.879 |
| SECONDARY Change From Baseline in EQ-5D-5L Thermometer Scores at Weeks 96 and 144 |
0.7; 1.9; 0.2; 1.4 | 0.102 |
Summary
The aim of the study is to establish if human immunodeficiency virus type 1 (HIV-1) infected adult participants with current virologic suppression on a >=3-drug tenofovir alafenamide (TAF) based regimen (TBR) remain suppressed upon switching to a two-drug regimen of dolutegravir (DTG) 50 milligram (mg) + lamivudine (3TC) 300 mg. This study will also provide important information regarding the safety and participant satisfaction with this two-drug regimen. The primary objective of this trial is to demonstrate the non-inferior antiviral activity of switching to DTG + 3TC once daily compared to continuation of TBR over 48 weeks in HIV-1 infected, antiretroviral therapy (ART)-experienced, virologically suppressed participants. This study also will characterize the long-term antiviral activity, tolerability and safety of DTG + 3TC compared to TBR through Week 144 and characterize the long-term antiviral activity, tolerability and safety of DTG + 3TC through Week 200.
This will be a 200-week, Phase III, randomized, open-label, active-controlled, multicenter, parallel- group study. The study will include a screening phase (up to 28 days), a randomized early switch phase (Day 1 up to Week 148), a randomized late switch phase (Week 148 up to Week 200), and a continuation phase (post Week 200). HIV-1 infected adults on stable TBR will be randomized 1:1 to switch to DTG + 3TC once daily for up to 200 weeks, or to continue their TBR for 148 weeks, at which time and if HIV-1 ribonucleic acid (RNA) <50 copies per milliliter (c/mL) at Week 144, these participants will switch to DTG + 3TC up to Week 200.
Eligibility Criteria
Inclusion Criteria
- Participant must be able to understand and comply with protocol requirements, instructions, and restrictions;
- Participant must be likely to complete the study as planned;
- Participant must be considered an appropriate candidate for participation in an investigative clinical trial with medication (example no active substance abuse, acute major organ disease, or planned long-term work assignments out of the country).
- Aged 18 years or older (or older where required by local regulatory agencies), at the time of signing the informed consent.
- HIV-1 infected men or women.
- Documented evidence of at least two plasma HIV-1 RNA measurements =5 times (*) the upper limit of normal (ULN) or ALT >=3 * ULN and bilirubin >=1.5 * ULN (with >35 percent [%] direct bilirubin).
- Creatinine clearance of 200 c/mL.
- Within the 6 to 12 month window prior to Screening and after confirmed suppression to =50 c/mL.
- Within 6 months prior to Screening and after confirmed suppression to =50 c/mL.
- 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.
- 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 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.
Data sourced from ClinicalTrials.gov (NCT03446573). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.