Phase 3
Completed N=183
A Study to Assess Dolutegravir in HIV-infected Subjects With Treatment Failure on an Integrase Inhibitor Containing Regimen.
Infection, Human Immunodeficiency Virus
Source: ClinicalTrials.gov NCT01328041 ↗
Enrolled (actual)
183
Serious AEs
25.1%
Results posted
Jul 2014
Primary outcomePrimary: Mean Change From Baseline in Plasma HIV-1 RNA at Day 8 — -1.432 log10 copies/milliliter (mL) — p=<0.001
Summary
The purpose of this trial is to assess the antiviral activity and safety of a dolutegravir (DTG) containing regimen in HIV-1 infected, antiretroviral therapy (ART)-experienced adults with current or historical failure on an integrase inhibitor (INI) containing regimen. The study will assess DTG 50mg twice daily administered initially with the current failing ART regimen but then with an optimised background ART regimen (OBR) after Day 7. The first analyses will be conducted after the last subject enrolled has completed 24 weeks. Subjects may remain on study after Week 24.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Mean Change From Baseline in Plasma HIV-1 RNA at Day 8 |
-1.432 | <0.001 sig |
| PRIMARY Number of Participants With HIV-1 RNA Less Than 50 Copies/mL at Week 24 |
126 | — |
| PRIMARY Number of Participants With HIV-1 RNA Less Than 50 Copies/mL at Week 48 |
116 | — |
| PRIMARY Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE) |
169; 46 | — |
| PRIMARY Number of Participants With Adverse Events of the Indicated Severity, Per the Division of Acquired Immune Deficiency Syndrome (DAIDS) Grading Scale |
45; 64; 44; 16 | — |
| PRIMARY Number of Participants With the Maximum Post-Baseline-emergent Clinical Chemistry Toxicities of the Indicated Grade |
49; 67; 43; 16 | — |
| PRIMARY Number of Participants With the Maximum Post-Baseline-emergent Hematology Toxicities of the Indicated Grade |
31; 15; 4; 2 | — |
| SECONDARY Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL at Baseline; Day 8; and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 |
1; 28; 98; 112; 116; 116 | — |
| SECONDARY Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL From Week 48 Every 12 Weeks up to Study Completion |
121; 110; 116; 108; 101; 81 | — |
| SECONDARY Mean Change From Baseline in Plasma HIV-1 RNA at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks up to Study Completion |
-1.432; -2.088; -2.101; -2.113; -2.216; -2.211 | — |
| SECONDARY Absolute Values for CD4+ Cell Counts at Baseline, Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 and for CD8+ Cell Counts at Baseline and Weeks 4, 12, 24, and 48 |
140.0; 170.0; 185.0; 210.0; 210.0; 210.0 | — |
| SECONDARY Median Change From Baseline in CD4+ Cell Counts at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks Until Study Completion |
20.0; 30.0; 40.0; 50.0; 60.0; 61.0 | — |
| SECONDARY Ratio of CD4+/CD8+ Cell Count at Baseline and Weeks 4, 12, 24, and 48 |
0.15; 0.19; 0.21; 0.26; 0.32 | — |
| SECONDARY Number of Participants With HIV-1 Disease Progression (Acquired Immune Deficiency Syndrome [AIDS] or Death) |
1; 2; 6; 2 | — |
| SECONDARY Cmax and Ctau of DTG |
4.74; 2.60 | — |
| SECONDARY AUC(0-tau) and AUC(0-24) of DTG |
36.7; 73.5 | — |
| SECONDARY C0 Assessment of DTG |
2.36; 1.90; 2.14 | — |
| SECONDARY Number of Participants With the Indicated Treatment-emergent Integrase (IN) Mutations Detected at the Time of Protocol-defined Virologic Failure (PDVF) as a Measure of Genotypic Resistance |
25; 8; 4; 1; 1; 3 | — |
| SECONDARY Number of Participants With the Indicated Fold Increase in DTG FC (Fold Change in IC50 Relative to Wild-type Virus) Between Baseline and the Time of PDVF, as a Measure of Post-Baseline Phenotypic Resistance |
6; 16; 4; 4; 12; 3 | — |
Eligibility Criteria
Inclusion Criteria
- Screening plasma HIV-1 RNA ≥500 copies/mL
- ART-experienced, INI-experienced, DTG naïve
- Experienced virological failure on raltegravir (RAL) or elvitegravir (ELV) regimen
- The subject's HIV-1 shows resistance to RAL or ELV at Screening or at prior time point of virological failure on RAL or ELV
- Documented resistance to at least one drug from each of three or more of all approved classes of ART
- Be able to receive at least one fully active drug as part of the OBR from Day 8
- Women capable of becoming pregnant must use appropriate contraception during the study (as defined by the protocol)
- Willing and able to understand and provide signed and dated written informed consent prior to Screening.
Exclusion Criteria
- Women who are pregnant or breast feeding
- An active AIDS-defining condition at Screening (except cutaneous Kaposi's sarcoma not requiring systemic therapy or CD4+ 5 times the upper limit of normal (ULN) at Screening
- ALT ≥ 3X ULN and bilirubin > 1.5 X ULN (with 35% direct bilirubin) at Screening
Data sourced from ClinicalTrials.gov (NCT01328041). 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. Informational only — not medical advice.