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Trial record 2 of 3 for:    Sword | HIV
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Regimen Switch to Dolutegravir + Rilpivirine From Current Antiretroviral Regimen in Human Immunodeficiency Virus Type 1 Infected and Virologically Suppressed Adults (SWORD-2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02422797
Recruitment Status : Active, not recruiting
First Posted : April 21, 2015
Results First Posted : October 24, 2017
Last Update Posted : December 14, 2021
Sponsor:
Collaborators:
Janssen Pharmaceuticals
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare

Study Description
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Brief Summary:
The aim of this study is to determine if virologically suppressed, human immunodeficiency virus type 1 (HIV-1) infected adults on an antiretroviral regimen (including 2 nucleoside reverse transcriptase inhibitors [NRTIs] plus a third agent) remain suppressed upon switching to a two-drug regimen with dolutegravir (DTG) + rilpivirine (RPV). The study will primarily assess the non-inferiority antiviral activity of switching to DTG + RPV once daily compared to continuation of current antiretroviral regimen (CAR) up to Week 48 with a switch visit for eligible subjects in the CAR group to initiate DTG + RPV therapy at Week 52. CAR will include 2 NRTIs plus 1 HIV-1 integrase inhibitor (INI), or 1 non-nucleoside reverse transcriptase inhibitor (NNRTI), or 1 protease inhibitor (PI). The study will include a 148-week open-label treatment phase, comprising of an Early Switch Phase (Day 1 to Week 52) and a Late Switch Phase (Week 52 to Week 148). The participants fulfilling the study eligibility criteria will participate in the Early Switch Phase where they will either switch from their CAR to DTG + RPV, or continue taking their CAR, until Week 52. At the end of Early Switch Phase, eligible participants will proceed to the Late Switch Phase where all participants in both DTG + RPV and CAR treatment groups will receive DTG + RPV therapy until Week 148. After Week 148, subjects may be eligible to continue to receive DTG +RPV in the Continuation Phase. The study is planned to be conducted in approximately 476 participants.

Condition or disease Intervention/treatment Phase
HIV Infections Drug: DTG 50 mg Drug: RPV 25 mg Drug: CAR Phase 3

Study Design
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Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 518 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III, Randomized, Multicenter, Parallel-group, Non-inferiority Study Evaluating the Efficacy, Safety, and Tolerability of Switching to Dolutegravir Plus Rilpivirine From Current INI-, NNRTI-, or PI-based Antiretroviral Regimen in HIV-1-infected Adults Who Are Virologically Suppressed
Actual Study Start Date : April 21, 2015
Actual Primary Completion Date : September 16, 2016
Estimated Study Completion Date : June 30, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Participants receiving CAR
Participants will receive CAR from Day 1 to Week 52 (Early Switch Phase), and eligible participants will switch to DTG 50 milligrams (mg) + RPV 25 mg once daily from Week 52 to 148 (Late Switch Phase).
 Drug: CAR
CAR will include following combinations: 2 NRTIs + 1 INI, 2 NRTIs + 1 NNRTI, or 2 NRTIs + 1 PI.
Experimental: Participants receiving DTG 50 mg + RPV 25 mg
Participants will receive DTG 50 mg + RPV 25 mg once daily from Day 1 through Week 148 (Early and Late Switch Phase).
 Drug: DTG 50 mg
Participants will take one oral tablet of 50 mg DTG daily administered concomitantly with RPV. Each DTG tablet will contain 52.62 mg dolutegravir sodium salt, which is equivalent to 50 mg dolutegravir free acid.

Drug: RPV 25 mg
Participants will take one oral tablet of 25 mg RPV daily administered concomitantly with DTG along with a meal. Each RPV tablet will contain 27.5 mg of rilpivirine hydrochloride, which is equivalent to 25 mg of RPV.


Outcome Measures
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Primary Outcome Measures :
  1. Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 48 Using Snapshot Algorithm [ Time Frame: Week 48 ]
    Percentage of participants with plasma HIV 1 RNA < 50 c/mL at Week 48 using the Food and Drug Administration (FDA) snapshot algorithm was assessed to demonstrate the non-inferior antiviral activity of switching to DTG+RPV once daily compared to continuation of CAR over 48 weeks in HIV-1 infected antiretroviral therapy (ART)-experienced participants. Virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment within the window of the visit of interest. Plasma samples were collected for quantitative analysis of HIV-1 RNA. The Intent-to-Treat Exposed (ITT-E) population consisted of all randomly assigned participants who received at least one dose of study drug.


Secondary Outcome Measures :
  1. Changes From Baseline in Cluster Designation (CD)4+ Lymphocyte Count at Weeks 24 and 48 [ Time Frame: Baseline (Day 1), Weeks 24 and 48 ]
    Blood samples were collected and CD4+ cell count assessment by flow cytometry was carried out to evaluate the immunological activity of DTG + RPV once daily compared to continuation of CAR. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  2. Percentage of Participants With Plasma HIV 1 RNA <50 c/mL at Week 24 Using Snapshot Algorithm [ Time Frame: Week 24 ]
    Percentage of participants with plasma HIV 1 RNA <50 c/mL at Week 24 using the FDA snapshot algorithm was assessed to evaluate the antiviral activity of DTG +RPV once daily compared to continuation of CAR. Virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment within the window of the visit of interest. Plasma samples were collected for quantitative analysis of HIV-1 RNA.

  3. Number of Participants With Common Non-serious Adverse Event (AE), Any Serious AE (SAE), AE of Maximum Toxicity Grade 1, 2, 3 or 4 and AE Leading to Discontinuation (AELD) [ Time Frame: Up to Week 52 ]
    An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with use of a medicinal product, whether or not considered related to medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention were categorized as SAE. AEs were graded using the Division of Acquired Immunodeficiency Syndrome (DAIDS) grading. Grade 1=mild; Grade 2=moderate, Grade 3=severe and Grade 4=potentially life-threatening. Common AEs were those with >5% incidence for either treatment. This summary presents results as reported after all participants completed the Early Switch Phase.

  4. Number of Participants With Maximum Post-baseline Emergent Chemistry Toxicities Over 48 Weeks [ Time Frame: Up to 48 weeks ]
    Blood samples were collected to evaluate alanine aminotransferase (ALT), albumin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), total bilirubin, chloride, creatinine, glucose, potassium, phosphate, sodium, blood urea nitrogen (BUN), total carbon dioxide, lipase, creatine phosphokinase and creatinine clearance. Value obtained at Day 1 was considered as Baseline value. Number of participants who experienced maximum grade toxicity post-baseline in clinical chemistry over 48 weeks was summarized. Clinical chemistry toxicities were graded using the Division of AIDS Table for Grading Severity of Adult and Pediatric Adverse Events. Grade 1=mild; Grade 2=moderate, Grade 3=severe and Grade 4=potentially life-threatening. For all laboratory parameters, one assessment out of range was sufficient to be considered a chemistry toxicity.

  5. Number of Participants With Maximum Post-baseline Emergent Hematology Toxicities Over 48 Weeks [ Time Frame: Up to 48 weeks ]
    Blood samples were collected to evaluate hemoglobin, hematocrit, basophils, eosinophils, lymphocytes, monocytes, neutrophils, mean corpuscular volume (MCV), red blood cell (RBC) count, white blood cell (WBC) count and platelet count. Value obtained at Day 1 was considered as Baseline value. Number of participants who experienced maximum grade toxicity post-baseline in hematology over 48 weeks was summarized. Hematology toxicities were graded using the Division of AIDS Table for Grading Severity of Adult and Pediatric Adverse Events. Grade 1=mild; Grade 2=moderate, Grade 3=severe and Grade 4=potentially life-threatening. For all laboratory parameters, one assessment out of range was sufficient to be considered a hematology toxicity.

  6. Mean Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) at Week 48 [ Time Frame: Baseline (Day 1) and Week 48 ]
    Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess hs-CRP. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  7. Mean Change From Baseline in Cystatin C at Week 48 [ Time Frame: Baseline (Day 1) and Week 48 ]
    Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess cystatin C. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  8. Mean Change From Baseline in D-Dimer at Week 48 [ Time Frame: Baseline (Day 1) and Week 48 ]
    Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess D-Dimer. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  9. Mean Change From Baseline in Fatty Acid Binding Protein 2 (FABP) and Soluble CD14 at Week 48 [ Time Frame: Baseline (Day 1) and Week 48 ]
    Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess FABP and soluble CD14. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  10. Mean Change From Baseline in Soluble CD163 and Oxidized Low Density Lipoprotein (LDL) at Week 48 [ Time Frame: Baseline (Day 1) and Week 48 ]
    Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess soluble CD163 and oxidized LDL. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  11. Mean Change From Baseline in Retinol Binding Protein (RBP), Serum Creatinine and Glucose at Week 48 [ Time Frame: Baseline (Day 1) and Week 48 ]
    Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess RBP, serum creatinine and glucose. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  12. Mean Change From Baseline in Urine Phosphate at Week 48 [ Time Frame: Baseline (Day 1) and Week 48 ]
    Urine biomarker samples were collected to at Baseline (Day 1) and Week 48 to assess urine phosphate. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  13. Mean Change From Baseline in Beta-2-microglobulin (B2M) (Blood and Urine), Urine RBP and 25 Hydroxy-vitamin D (Blood) at Week 48 [ Time Frame: Baseline (Day 1) and Week 48 ]
    Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess B2M and 25 hydroxy-vitamin D. Urine biomarker samples were collected to assess B2M and RBP. Change from Baseline was calculated as value at indicated time point minus Baseline value. For 25 hydroxy-vitamin D, analysis of changes from Baseline was performed on log-transformed data. Results were transformed back via exponential transformation such that treatment comparisons are assessed via odds ratios.

  14. Mean Change From Baseline in Urine Albumin/Creatinine Ratio and Urine Protein/Creatinine Ratio at Week 48 [ Time Frame: Baseline (Day 1) and Week 48 ]
    Urine biomarker samples were collected at Baseline (Day 1) and Week 48 to assess urine albumin/creatinine ratio and urine protein/creatinine ratio. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  15. Mean Change From Baseline in Bone-specific Alkaline Phosphatase, Procollagen 1 N-terminal Propeptide, Osteocalcin, Type 1 Collagen C-telopeptides and Soluble Vascular Cell Adhesion Molecule (sVCAM) at Week 48 [ Time Frame: Baseline (Day 1) and Week 48 ]
    Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess bone-specific alkaline phosphatase, procollagen 1 N-terminal propeptide, osteocalcin, Type 1 Collagen C-telopeptides and sVCAM. Change from Baseline was calculated as value at indicated time point minus Baseline value. For bone-specific alkaline phosphatase, procollagen 1-N-propeptide, osteocalcin and type 1 collagen C-telopeptide, analyses of changes from Baseline were performed on log-transformed data. Results were transformed back via exponential transformation such that treatment comparisons are assessed via odds ratios.

  16. Mean Change From Baseline in Interleukin 6 (IL-6) at Week 48 [ Time Frame: Baseline (Day 1) and Week 48 ]
    Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess IL-6. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  17. Mean Change From Baseline in Insulin Resistance Based on Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) at Week 48 [ Time Frame: Baseline (Day 1) and Week 48 ]
    Blood biomarker samples were collected at Baseline (Day 1) and Week 48 to assess insulin resistance. Change from Baseline was calculated as value at indicated time point minus Baseline value. The homeostatic model assessment (HOMA) of insulin resistance (HOMA-IR ) index , the product of basal glucose and insulin levels divided by 22.5, is regarded as a simple, inexpensive, and reliable surrogate measure of insulin resistance.

  18. Mean Change From Baseline in Fasting Lipids at Weeks 24 and 48 [ Time Frame: Baseline (Day 1), Weeks 24 and 48 ]
    Blood samples were collected at Baseline (Day 1), Week 24 and Week 48 to assess fasting lipids which included total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol and triglycerides. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  19. Number of Participants With Genotypic Resistance-Early Switch Phase [ Time Frame: Up to Week 48 ]
    Plasma samples were collected for drug resistance testing. Genotypic Resistance data for the following drugs (Rilpivirine [RPV], Dolutegravir [DTG]) in participants Meeting Confirmed Virologic Withdrawal (CVW) criteria has been presented. CVW resistance Population comprised of all participants in the ITT-E Population who met CVW through the end of visit window (Week 48, Week 100 or Week 148) and have available on-treatment genotypic resistance data at the time CVW criterion is met.

  20. Number of Participants With Genotypic Resistance-DTG+RPV Early Switch Arm Through Early and Late Switch Phase [ Time Frame: Up to Week 148 ]
    Plasma samples were collected for drug resistance testing. Genotypic Resistance data for the following drugs (DTG, Elvitegravir [EVG], Raltegravir [RAL], Delavirdine [DLV], Efavirenz [EFV], Etravirine [ETR], Nevirapine [NVP], RPV, Lamivudine [3TC], Abacavir [ABC], FTC, TDF, Zidovudine [ZDV], Stavudine [d4T], Didanosine [ddI], Atazanavir/r [ATV/r], DRV/r, Fosamprenavir/r [FPV/r], Indinavir/r [IDV/r], Lopinavir/r [LPV/r], Nelfinavir [NFV], Ritonavir [RTV], Saquinavir/r [SQV/r], Tipranavir/r [TPV/r]) in participants Meeting Confirmed Virologic Withdrawal Criteria has been presented.

  21. Number of Participants With Genotypic Resistance-CAR Late Switch Arm Through Late Switch Phase [ Time Frame: Post-LS Baseline (Week 52) up to Week 148 ]
    Plasma samples were collected for drug resistance testing. Genotypic Resistance data for the following drugs (DTG, EVG, RAL, DLV, EFV, ETR, NVP, RPV, 3TC, ABC, FTC, TDF, ZDV, d4T, ddI, ATV/r, DRV/r, FPV/r, IDV/r, LPV/r, NFV, RTV, SQV/r, TPV/r) in participants Meeting CVW Criteria has been presented. Late Switch (LS) CVW resistance Population comprised of all participants in the LS ITT-E Population who met CVW through the end of visit window (Week 48, Week 100 or Week 148) and had available on-treatment genotypic resistance data at the time CVW criterion is met.

  22. Number of Participants With Phenotypic Resistance-Early Switch Phase [ Time Frame: Up to Week 48 ]
    Plasma samples were collected for drug resistance testing. Phenotypic Resistance data for the following drugs (DTG, RAL, EVG, RPV, ETR, 3TC, ABC, FTC, TDF, d4T, ddI, ATV/r, DRV/r, FPV/r, IDV/r, LPV/r, SQV/r, TPV/r) in participants Meeting CVW criteria has been presented.

  23. Number of Participants With Phenotypic Resistance-DTG+RPV Early Switch Group Through Early and Late Switch Phase [ Time Frame: Up to Week 148 ]
    Plasma samples were collected for drug resistance testing. Phenotypic Resistance data for the following drugs (DTG, EVG, RAL, DLV, EFV, ETR, NVP, RPV, 3TC, ABC, FTC, TDF, ZDV, d4T, ddI, ATV/r, DRV/r, FPV/r, IDV/r, LPV/r, NFV, RTV, SQV/r, TPV/r) in participants Meeting CVW criteria has been presented.

  24. Number of Participants With Phenotypic Resistance-CAR Late Switch Group Through Late Switch Phase [ Time Frame: Post-LS Baseline (Week 52) up to Week 148 ]
    Plasma samples were collected for drug resistance testing. Phenotypic Resistance data for the following drugs (DTG, EVG, RAL, DLV, EFV, ETR, NVP, RPV, 3TC, ABC, FTC, TDF, ZDV, d4T, ddI, ATV/r, DRV/r, FPV/r, IDV/r, LPV/r, NFV, RTV, SQV/r, TPV/r) in participants Meeting CVW criteria has been presented.

  25. Pre-dose Concentrations of DTG and RPV at Weeks 4, 24, 48, 56, 76 and 100 in Participants Switching to DTG + RPV - DTG+RPV Early Switch Group Through Early and Late Switch Phase [ Time Frame: Pre-dose at Week 4, 24, 48, 56, 76 and 100 ]
    Two separate blood samples for DTG and RPV were collected pre-dose at Weeks 4, 24, 48, 56, 76 and 100. Pre-dose concentrations of DTG and RPV at Weeks 4, 24, 48, 56, 76 and 100 is summarized for the participants switching to DTG + RPV in the early+late switch phase. Pharmacokinetic (PK) Parameter Population consisted of all participants who received DTG +RPV and provided at least one evaluable estimate of predose concentration (C0).

  26. Pre-dose Concentrations of DTG and RPV at Weeks 56, 76 and 100 in Participants Switching to DTG + RPV - CAR Late Switch Group Through Late Switch Phase [ Time Frame: Pre-dose at Weeks 56, 76 and 100 ]
    Two separate blood samples for DTG and RPV were collected pre-dose at Weeks 56, 76 and 100. Pre-dose concentrations of DTG and RPV at Weeks 56, 76 and 100 is summarized for the participants switching to DTG + RPV in the late switch phase. LS PK Parameter Population comprised of all participants who were randomized to CAR and received DTG + RPV in the Late Switch Phase and provided at least one evaluable estimate of C0.

  27. Pre-dose Concentrations of DTG and RPV at Weeks 2, 4 and 8 in the First 20 Participants Who Switch From Efavirenz (EFV) or Nevirapine (NVP) to DTG + RPV [ Time Frame: Pre-dose at Weeks 2, 4 and 8 ]
    Two blood samples were collected pre-dose for DTG and RPV at Weeks 2 and 8 only for the first 20 participants who switch from EFV or NVP to DTG+RPV, in addition to the pre-dose blood sample collected at Week 4 for all participants. One blood sample was collected pre-dose for EFV or NVP at Week 2 for the first 20 participants who switch from EFV or NVP to DTG + RPV. PK Parameter NNRTI Subset Extra Sampling Population consisted of the first approximately 20 participants in the PK Parameter NNRTI Subset population who have extra PK samples at weeks 2 and 8.

  28. Percentage of Participants With Plasma HIV 1 RNA <50 c/mL at Week 48 Using Snapshot Algorithm by Baseline Third Agent Treatment Class [ Time Frame: Up to Week 48 ]
    Percentage of participants with plasma HIV 1 RNA < 50 c/mL at Week 48 using the FDA snapshot algorithm was assessed by Baseline third agent class to assess the impact of Baseline third agent class (INSTI, NNRTI, or PI) on efficacy, safety and tolerability of DTG +RPV compared to continuation of CAR. Plasma samples were collected for HIV-1 RNA at Baseline (Day 1), Week 4, 8, 12, 24, 36 and 48. The analysis was done using Cochran-Mantel Haenszel test stratified by current antiretroviral third-agent class.

  29. Changes From Baseline in CD4+ Lymphocyte Count at Week 48 by Baseline Third Agent Treatment Class [ Time Frame: Baseline (Day 1) and Week 48 ]
    Blood samples were collected and CD4+ cell count assessment by flow cytometry was carried out at Baseline (Day 1) and Week 48 to assess the impact of Baseline third agent class (INSTI, NNRTI, or PI) on efficacy, safety and tolerability of DTG +RPV compared to continuation of CAR. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  30. Number of Participants With Any AE, AELD or AE With Grade 1, 2, 3 or 4 Toxicity Over 48 Weeks by Baseline Third Agent Treatment Class [ Time Frame: Up to 48 weeks ]
    An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with any AE, AELD or AE with maximum grade toxicity experienced by any one participant over 48 weeks by Baseline third agent class (INSTI, NNRTI, or PI) is summarized. AEs were graded using the Division of AIDS grading. Grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=potentially life-threatening.

  31. Number of Participants With Maximum Post-baseline Emergent Chemistry Toxicities Over 48 Weeks by Baseline Third Agent Treatment Class [ Time Frame: Up to 48 weeks ]
    Blood samples were collected at Baseline (Day 1) and at Weeks 4, 8, 12, 24, 36 and 48 to evaluate ALT, albumin, ALP, AST, total bilirubin, chloride, creatinine, glucose, potassium, phosphate, sodium, BUN, total carbon dioxide, lipase, creatine phosphokinase and creatinine clearance. Number of participants who experienced maximum toxicity grade post-baseline in chemistry parameters over 48 weeks by Baseline third agent treatment class (INSTI, NNRTI, PI) is summarized. Clinical chemistry toxicities were graded using the DAIDS grading. Grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=potentially life-threatening.

  32. Number of Participants With Maximum Post-baseline Emergent Hematology Toxicities Over 48 Weeks by Baseline Third Agent Treatment Class [ Time Frame: Up to 48 weeks ]
    Blood samples were collected at Baseline (Day 1) and at Weeks 4, 8, 12, 24, 36 and 48 to evaluate hemoglobin, hematocrit, basophils, eosinophils, lymphocytes, monocytes, neutrophils, MCV, RBC count, WBC count and platelet count. Number of participants who experienced maximum toxicity grade post-baseline in hematology parameters over 48 weeks by Baseline third agent treatment class (INSTI, NNRTI, PI) was summarized. Hematology toxicities were graded using the DAIDS grading. Grade 1=mild; grade 2=moderate; grade 3=severe; grade 4=potentially life-threatening.

  33. Number of Participants With Observed Genotypic Resistance for Participants Meeting Virologic Withdrawal Criteria by Baseline Third Agent Treatment Class [ Time Frame: Week 48 ]
    For all participants who meet virologic withdrawal criteria, plasma samples with HIV-1 RNA level >=200 c/mL were to be analyzed in an attempt to obtain genotype data on as many samples as possible. Samples for drug resistance testing (genotypic) were to be collected at Day 1. Number of participants with genotypic resistance to CAR and to DTG or RPV for those meeting virologic withdrawal criteria in subgroups stratified based on Baseline third agent treatment class (INSTI, NNRTI, PI) were to be summarized. This outcome has not been analyzed as the number of participants was low (1 CVW per arm) and summaries by Baseline third agent were not provided. Therefore, data are not available for this outcome measure due to the insufficient number of participants with events.

  34. Number of Participants With Observed Phenotypic Resistance for Participants Meeting Virologic Withdrawal Criteria by Baseline Third Agent Treatment Class [ Time Frame: Week 48 ]
    For all participants who meet virologic withdrawal criteria, plasma samples with HIV-1 RNA level >=200 c/mL were to be analyzed in an attempt to obtain phenotype data on as many samples as possible. Samples for drug resistance testing (phenotypic) were to be collected at Day 1. Number of participants with phenotypic resistance to CAR and to DTG or RPV for those meeting virologic withdrawal criteria in subgroups stratified based on Baseline third agent treatment class (INSTI, NNRTI, PI) were to be summarized. This outcome was not analyzed as the number of participants was low (1 CVW per arm) and summaries by Baseline third agent were not provided. Therefore, data are not available for this outcome measure due to the insufficient number of participants with events.

  35. Change From Baseline in Fasting Lipids at Weeks 24 and 48 by Baseline Third Agent Treatment Class [ Time Frame: Baseline (Day 1), Weeks 24 and 48 ]
    Blood samples were collected at Baseline (Day 1), Weeks 24 and 48 to assess fasting lipids which included total cholesterol (CHO), LDL cholesterol, HDL cholesterol and triglycerides. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  36. Change From Baseline in Pre-specified Treatment Symptoms Using the Symptom Distress Module at Weeks 4, 24 and 48-Early Switch Phase [ Time Frame: Baseline (Day 1), Weeks 4, 24 and 48 ]
    The Symptom Distress Module, also called the HIV Symptom Index or Symptoms Impact Questionnaire, is a 20-item self-reported measure that addresses the presence and perceived distress linked to symptoms commonly associated with HIV or its treatment. Symptom count is based on which of the 20 symptoms were present in the participant. Symptom count is the sum of the number of symptoms present and ranges from 0 (none) to 20 (all). Symptom bother score is based on the score for each symptom present ranging from 1 (it doesn't bother me) to 4 (it bothers me a lot). Symptom bother score is the unweighted sum of the bother item scores for each symptom. The symptom bother score ranges from 0 (minimum bother score) to 80 (maximum bother score). Last observation carried forward (LOCF) was used as primary method of analysis. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  37. Change From Baseline in Pre-specified Treatment Symptoms Using the Symptom Distress Module at Weeks 56, 76, 100 and 148-DTG+RPV Early Switch Group Through Early and Late Switch Phase [ Time Frame: Baseline (Day 1), Weeks 56, 76, 100 and 148 ]
    The Symptom Distress Module, also called the HIV Symptom Index or Symptoms Impact Questionnaire, is a 20-item self-reported measure that addresses the presence and perceived distress linked to symptoms commonly associated with HIV or its treatment. Symptom count is based on which of the 20 symptoms were present in the participant. Symptom count is the sum of the number of symptoms present and ranges from 0 (none) to 20 (all). Symptom bother score is based on the score for each symptom present ranging from 1 (it doesn't bother me) to 4 (it bothers me a lot). Symptom bother score is the unweighted sum of the bother item scores for each symptom. The symptom bother score ranges from 0 (minimum bother score) to 80 (maximum bother score). LOCF was used as primary method of analysis. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  38. Change From LS Baseline in Pre-specified Treatment Symptoms Using the Symptom Distress Module at Weeks 56, 76, 100 and 148-CAR Late Switch Group Through Late Switch Phase [ Time Frame: LS Baseline (Week 48), Weeks 56, 76, 100 and 148 ]
    The Symptom Distress Module, also called the HIV Symptom Index or Symptoms Impact Questionnaire, is a 20-item self-reported measure that addresses the presence and perceived distress linked to symptoms commonly associated with HIV or its treatment. Symptom count is based on which of the 20 symptoms were present in the participant. Symptom count is the sum of the number of symptoms present and ranges from 0 (none) to 20 (all). Symptom bother score is based on the score for each symptom present ranging from 1 (it doesn't bother me) to 4 (it bothers me a lot). Symptom bother score is the unweighted sum of the bother item scores for each symptom. The symptom bother score ranges from 0 (minimum bother score) to 80 (maximum bother score). LOCF was used as primary method of analysis. Change from LS Baseline was calculated as value at indicated time point minus LS Baseline value.

  39. Change From Baseline Treatment Satisfaction Using the HIV Treatment Satisfaction Questionnaire (HIV TSQ) at Weeks 4, 24 and 48-Early Switch Phase [ Time Frame: Baseline (Day 1), Weeks 4, 24 and 48 ]
    The HIV TSQ is a 10-item self-reported scale that measures overall satisfaction with treatment and by specific domains e.g., convenience, flexibility. Each item is scored 0 to 6 where a higher score indicates the greater improvement in the past few weeks. These items are summed up to produce a treatment satisfaction total score (0 to 60) and 2 subscales: general satisfaction/clinical and lifestyle/ease subscales (0 to 30). The HIV TSQ was administered as a paper questionnaire. Total score, lifestyle/ease score and General satisfaction/clinical sub-score (CS) have been summarized. LOCF was used as primary method of analysis. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  40. Change From Baseline Treatment Satisfaction Using the HIV TSQ at Weeks 56, 76, 100 and 148-DTG+RPV Early Switch Group Through Early and Late Switch Phase [ Time Frame: Baseline (Day 1), Weeks 56, 76, 100 and 148 ]
    The HIV TSQ is a 10-item self-reported scale that measures overall satisfaction with treatment and by specific domains e.g., convenience, flexibility. Each item is scored 0 (very dissatisfied, inconvenient) to 6 (very satisfied, convenient). The items are summed up to produce a treatment satisfaction total score (0 to 60) and 2 subscale scores: general satisfaction/clinical and lifestyle/ease subscales (0 to 30). Higher scores indicated greater treatment satisfaction as compared to the past few weeks. The HIV TSQ was administered as a paper questionnaire. Change from Baseline is calculated as the value at specified time point minus Baseline value. Total score, lifestyle/ease score and General satisfaction/clinical sub-score (CS) have been summarized. LOCF was used as primary method of analysis.

  41. Change From LS Baseline Treatment Satisfaction Using the HIV TSQ at Weeks 56, 76, 100 and 148-CAR Late Switch Group Through Late Switch Phase [ Time Frame: LS Baseline (Week 48), Weeks 56, 76, 100 and 148 ]
    The HIV TSQ is a 10-item self-reported scale that measures overall satisfaction with treatment and by specific domains e.g., convenience, flexibility. Each item is scored 0 (very dissatisfied, inconvenient) to 6 (very satisfied, convenient). The items are summed up to produce a treatment satisfaction total score (0 to 60) and 2 subscale scores: general satisfaction/clinical and lifestyle/ease subscales (0 to 30). Higher scores indicated greater treatment satisfaction as compared to the past few weeks. The HIV TSQ was administered as a paper questionnaire. Change from LS Baseline is calculated as the value at specified time point minus LS Baseline value. Total score, lifestyle/ease score and General satisfaction/CS have been summarized. LOCF was used as primary method of analysis.


Other Outcome Measures:
  1. Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Weeks 100 and 148 Using the Snapshot Algorithm-DTG+RPV Early Switch Group Through Early and Late Switch Phase [ Time Frame: Weeks 100 and 148 ]
    Plasma samples were collected for quantitative analysis of HIV-1 RNA. Percentage of participants with plasma HIV 1 RNA < 50 c/mL using the FDA snapshot algorithm was assessed. Virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment within the window of the visit of interest.

  2. Change From Baseline in CD4+ Lymphocyte Count at Weeks 100 and 148-DTG+RPV Early Switch Group Through Early and Late Switch Phase [ Time Frame: Baseline (Day 1), Weeks 100 and 148 ]
    Blood samples were collected for CD4+ cell count assessment by flow cytometry. Change from Baseline was calculated as value at indicated time point minus Baseline value.

  3. Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Weeks 100 and 148 Using the Snapshot Algorithm-CAR Late Switch Group Through Late Switch Phase [ Time Frame: Weeks 100 and 148 ]
    Plasma samples were collected for quantitative analysis of HIV-1 RNA. Percentage of participants with plasma HIV 1 RNA < 50 c/mL using the FDA snapshot algorithm was assessed. Virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment within the window of the visit of interest.

  4. Change From LS Baseline in CD4+ Lymphocyte Count at Weeks 100 and 148-CAR Late Switch Group Through Late Switch Phase [ Time Frame: LS Baseline (Week 48), Weeks 100 and 148 ]
    Blood samples were collected for CD4+ cell count assessment by flow cytometry. Change from LS Baseline was calculated as value at indicated time point minus LS Baseline value.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants must be able to understand and comply with protocol requirements, instructions, and restrictions.
  • Participants must be likely to complete the study as planned.
  • Participants must be considered appropriate candidates for participation in an investigative clinical trial with oral medication (e.g., no active substance abuse, acute major organ disease, or planned long-term work assignments out of the country, etc.).
  • HIV-1 infected men or women of >=18 years of age.
  • Must be on uninterrupted current regimen (either the initial or second combination antiretroviral therapy [cART] regimen) for at least 6 months prior to screening; 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. Acceptable stable cART regimens prior to screening include 2 NRTIs plus; INI (either the initial or second cART regimen), or an NNRTI (either the initial or second cART regimen), or a Boosted PI (or atazanavir unboosted) ( either the initial or second PI-based cART regimen).
  • 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;
  • A female may be eligible to enter and participate in the study if she is of : Non-child-bearing potential either defined as post-menopausal (12 months of spontaneous amenorrhea and >=45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy or child-bearing potential with a negative pregnancy test at both Screening and Day 1 and agrees to use one of the following methods of contraception to avoid pregnancy: Complete abstinence from intercourse from 2 weeks prior to administration of study drug, throughout the study, and for at least 2 weeks after discontinuation of all study medications and completion of the Follow-up visit; Any intrauterine device (IUD) with published data showing that the expected failure rate is <1% per year (not all IUDs meet this criterion); Male partner sterilization with documentation of azoospermia prior to the female participant's entry into the study and this male is the sole partner for that participant. The documentation on male sterility can come from the site personnel's review of participant's medical records, medical examination, and/or semen analysis, or medical history interview provided by her or her partner; Approved hormonal contraception for participants randomly assigned to DTG + RPV arm (and for participants randomly assigned to CAR following switch to DTG + RPV at Week 52) or approved hormonal contraception plus a barrier method for participants assigned to CAR through Week 52. Approved hormonal contraception includes: Combined estrogen and progestogen oral contraceptive, Contraceptive subdermal implant, Injectable progestogen, Contraceptive vaginal ring, Percutaneous contraceptive patches; Any other method with published data showing that the expected failure rate is <1% per year. Any contraception method must be used consistently, in accordance with the approved product label during treatment with study drug and for at least 2 weeks after discontinuation of study drug and completion of the Follow-Up Visit. The investigator is responsible for ensuring that participants understand how to properly use these methods of contraception. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Note: these contraceptive requirements do not apply to females of reproductive potential with same sex partners only, when this is their preferred and usual lifestyle. All participants participating 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.
  • Participants who are willing and able to understand requirements of study participation and provide signed and dated written informed consent prior to screening.
  • For participants enrolled in France: participants will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria:

Exclusionary Criteria prior to screening or Day 1:

  • Within 6 months prior to Screening and after confirmed suppression to <50 c/mL on current Antiretroviral therapy (ART regimen), any plasma HIV-1 RNA measurement >=50 c/mL.
  • Within the 6 to 12 month window prior to screening and after confirmed suppression to <50 c/mL, any plasma HIV-1 RNA measurement >200 c/mL.
  • Within the 6 to 12 month window prior to screening and after confirmed suppression to <50 c/mL, 2 or more plasma HIV-1 RNA measurements >=50 c/mL.
  • Any drug holiday during the window between initiating first HIV ART and 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 switch to a second line 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 measurement >=400 c/mL after initial suppression to <50 c/mL while on first line HIV therapy regimen).

Exclusionary medical conditions:

  • Women who are pregnant, breastfeeding or plan to become pregnant or breastfeed during the study.
  • Any evidence of an active Centers for Disease Control and Prevention Category C disease. Exceptions include cutaneous Kaposi's sarcoma not requiring systemic therapy and historic CD4+ lymphocyte counts of <200 cells per cubic millimeter (cells/mm^3).
  • Participants with severe hepatic impairment (Class C) as determined by Child-Pugh Classification.
  • Unstable liver disease (as defined by the presence of any of the following: ascites, encephalopathy, coagulopathy, hypoalbuminemia, oesophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • 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), and Hepatitis B surface antibody (HBsAb) as follows: participants positive for HBsAg are excluded; participants positive for anti-HBc (negative HBsAg status) and negative for HBsAb are excluded. Note: Participants positive for anti-HBc (negative HBsAg status) and positive for HBsAb are immune to HBV and are not excluded.
  • Participants with an anticipated need for any Hepatitis C virus (HCV) therapy during the Early Switch Phase and for interferon-based therapy for HCV throughout the entire study period.
  • History or presence of allergy to the study drugs or their components or drugs of their class;
  • Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical intraepithelial neoplasia; other localized malignancies require agreement between the investigator and the Study medical monitor for inclusion of the participant prior to randomization;
  • Participants who in the investigator's judgment pose a significant suicidality risk. Participant's history of suicidal behavior and/or suicidal ideation should be considered when evaluating for suicide risk;
  • 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 drugs or render the participant unable to take oral medication;

Exclusionary Treatments prior to Screening or Day 1:

  • Use of medications which are associated with Torsades de Pointes.
  • Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening.
  • Treatment with any of the following agents within 28 days of Screening: radiation therapy; cytotoxic chemotherapeutic agents; any immunomodulators that alter immune responses.
  • 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 Day 1 of this study.
  • Participants who are currently participating, or are anticipated to be selected to participate in any other interventional study, with the exception of the DEXA sub-study 202094, after randomization (NOTE: Participants who are already enrolled into another interventional study at time of screening may be eligible after consultation with the GlaxoSmithKline study team prior to randomization. Considerations include participant's ability to attend all visits on schedule, and possible drug and study procedure compatibility).
  • A history of use of any regimen consisting of only single NNRTI therapy (even if only for peri-partum treatment), or only single or dual NRTI therapy prior to starting cART.
  • Current or prior history of etravirine (ETR) use.
  • Current use of tipranavir/ritonavir or fosamprenavir/ritonavir.
  • Participants receiving any prohibited medication and who are unwilling or unable to switch to an alternate medication. Note: Any prohibited medications that decrease DTG or RPV concentrations should be discontinued for a minimum of four weeks or a minimum of three half-lives (whichever is longer) prior to the first dose and any other prohibited medications should be discontinued for a minimum of two weeks or a minimum of three half-lives (whichever is longer) prior to the first dose.

Exclusionary Laboratory Values or Clinical Assessments at Screening:

  • Evidence of viral resistance based on the presence of any resistance associated major PI, INI, NRTI, or NNRTI mutation and integrase (IN) resistance associated substitution R263K in any available prior resistance genotype assay results. Note: Any prior genotypic resistance testing is not required but if available it must be provided to GlaxoSmithKline, after screening and before randomization, to provide direct evidence of no pre-existing exclusionary resistance mutations. You must wait for the study virologists to confirm the lack of exclusionary resistance mutations, which will be provided before the screening window closes.
  • 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.
  • Any acute laboratory abnormality at Screening, which, in the opinion of the investigator, would preclude the participant's participation in the study of an investigational compound.
  • Alanine aminotransferase (ALT) >=5 × upper limit of normal (ULN), or ALT >=3 × ULN and bilirubin >=1.5 × ULN (with >35% direct bilirubin).
  • Corrected QT interval (QTc [Bazett]) >450 milliseconds or QTc (Bazett) >480 milliseconds for participants with bundle branch block. The QTc is the QT interval corrected for heart rate according to Bazett's formula (QTcB).
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02422797


Locations
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Sponsors and Collaborators
ViiV Healthcare
Janssen Pharmaceuticals
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials ViiV Healthcare
More Information
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Publications:
Llibre JM, Hung CC, Brinson C, et al. Efficacy, safety, and tolerability of dolutegravir plus rilpivirine for the maintenance of virologic suppression in HIV-1-infected adults: the phase III, randomized, open-label, active-controlled, noninferiority SWORD-1 and SWORD-2 studies. Lancet [epublished ahead of print] 6 January 2018.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT02422797    
Other Study ID Numbers: 201637
2014-005148-16 ( EudraCT Number )
First Posted: April 21, 2015    Key Record Dates
Results First Posted: October 24, 2017
Last Update Posted: December 14, 2021
Last Verified: December 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: https://clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by ViiV Healthcare:
HIV
NNRTI-sparing
two-drug regimen
nucleoside reverse transcriptase inhibitors
protease inhibitor
 integrase inhibitor
non-nucleoside reverse transcriptase inhibitor
dolutegravir plus rilpivirine
virologically-suppressed
Additional relevant MeSH terms:
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HIV Infections
Blood-Borne Infections
Communicable Diseases
Infections
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Lentivirus Infections
 Retroviridae Infections
RNA Virus Infections
Virus Diseases
Genital Diseases
Urogenital Diseases
Immunologic Deficiency Syndromes
Immune System Diseases