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Trial record 2 of 3 for:    SWORD hiv

Regimen Switch to Dolutegravir + Rilpivirine From Current Antiretroviral Regimen in Human Immunodeficiency Virus Type 1 Infected and Virologically Suppressed Adults (SWORD-1)

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02429791
First Posted: April 29, 2015
Last Update Posted: December 1, 2017
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.
Collaborators:
Janssen Pharmaceuticals
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare
  Purpose
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 Intervention Phase
Infection, Human Immunodeficiency Virus Drug: DTG 50 mg Drug: RPV 25 mg Drug: CAR Phase 3

Study Type: Interventional
Study Design: 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 (SWORD-1)

Resource links provided by NLM:


Further study details as provided by ViiV Healthcare:

Primary Outcome Measures:
  • Percentage of Participants With Plasma Human Immunodeficiency Virus (HIV) 1 Ribonucleic Acid (RNA) <50 Copies/Milliliter (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 HIV-1 RNA at Baseline (Day 1), Week 4, 8, 12, 24, 36 and 48. Treatment with DTG + RPV was declared non-inferior to CAR if the lower end of a two-sided 95% confidence interval for the difference between the two groups in response rates at Week 48 lies above -10% by Cochran-Mantel Haenszel test. 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:
  • Changes From Baseline in Cluster Designation (CD)4+ Lymphocyte Count at Weeks 24 and 48 [ Time Frame: Week 24 and 48 ]
    Blood was collected and CD4+ cell count assessment by flow cytometery was carried out at Baseline (Day 1), Week 4, 8, 12, 24, 36 and 48 to evaluate the immunological activity of DTG + RPV once daily compared to continuation of CAR. The full set of lymphocyte sub sets was not evaluated. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).

  • 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 HIV-1 RNA at Baseline (Day 1), Week 4, 8, 12 and 24.

  • Number of Participants With Common Non-serious Adverse Event (AE), Any Serious AE (SAE), AE of Maximum Toxicity Grade 1, 2, 3 or 4, AE Leading to Discontinuation (AELD) [ Time Frame: Up to 52 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. 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. Number of participants with common non-serious AE, SAE, AELD or AE with maximum grade toxicity experienced over Week 48 was summarized. Common AEs were those with >5 percent incidence for either treatment. Safety Population included all randomly assigned participants who have received at least one dose of study drug.

  • Number of Participants With Maximum Post-baseline Emergent Chemistry Toxicities Over 48 Weeks [ Time Frame: Up to 48 weeks ]
    Blood samples were collected at Baseline (Day 1) and at Week 4, 8, 12, 24, 36 and 48 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. Change from Baseline was calculated as value at indicated time point minus Baseline value. Number of participants who experienced maximum grade toxicity post-baseline in clinical chemistry over 48 weeks was summarized. Participants 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; grade 4=potentially life-threatening.

  • Number of Participants With Maximum Post-baseline Emergent Hematology Toxicities Over 48 Weeks [ Time Frame: Up to 48 weeks ]
    Blood samples were collected at Baseline (Day 1) and at Week 4, 8, 12, 24, 36 and 48 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. Change from Baseline was calculated as value at indicated time point minus Baseline value. Number of participants who experienced maximum grade toxicity post-baseline in hematology over 48 weeks was summarized. Participants 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; grade 4=potentially life-threatening

  • Mean Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) at Week 48 [ Time Frame: Up to 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.

  • Mean Change From Baseline in Cystatin C at Week 48 [ Time Frame: Up to 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.

  • Mean Change From Baseline in D-Dimer at Week 48 [ Time Frame: Up to 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.

  • Mean Change From Baseline in Fatty Acid Binding Protein 2 (FABP) and Soluble CD14 at Week 48 [ Time Frame: Up to 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. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).

  • Mean Change From Baseline in Soluble CD163 and Oxidized Low Density Lipoprotein (LDL) at Week 48 [ Time Frame: Up to 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. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).

  • Mean Change From Baseline in Retinol Binding Protein (RBP), Serum Creatinine and Glucose at Week 48 [ Time Frame: Up to 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. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).

  • Mean Change From Baseline in Urine Phosphate at Week 48 [ Time Frame: Up to 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.

  • Mean Change From Baseline in Beta-2-microglobulin (B2M) (Blood and Urine), Urine RBP and 25 Hydroxy-vitamin D at Week 48 [ Time Frame: Up to 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 at Baseline (Day 1) and Week 48 to assess urine B2M and urine RBP. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles). 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.

  • Mean Change From Baseline in Urine Albumin/Creatinine Ratio and Urine Protein/Creatinine Ratio at Week 48 [ Time Frame: Up to 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. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).

  • Mean Change From Baseline in Bone-specific Alkaline Phosphatase, Procollagen 1 N-terminal Propeptide, Osteocalcin, Type I Collagen C-Telopeptides and Soluble Vascular Cell Adhesion Molecule (sVCAM) at Week 48 [ Time Frame: Up to 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 I Collagen C-Telopeptides and sVCAM. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles). 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.

  • Mean Change From Baseline in Interleukin 6 (IL-6) at Week 48 [ Time Frame: Up to 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.

  • Mean Change From Baseline in Insulin Resistance Based on Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) at Week 48 [ Time Frame: Up to 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 (1,2), is regarded as a simple, inexpensive, and reliable surrogate measure of insulin resistance.

  • Mean Change From Baseline in Fasting Lipids at Weeks 24 and 48 [ Time Frame: Up to Week 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. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).

  • Genotypic Resistance Data for Drugs Received for Participants Meeting Confirmed Virologic Withdrawal Criteria [ Time Frame: Day 1 ]
    Genotypic resistance data for drugs received for participants meeting confirmed virologic withdrawal criteria are presented below. Confirmed Virologic Withdrawal (CVW) Population consisted of all participants in the ITT-E Population who met CVW (1 CVW per arm). NA indicate that data were not applicable based on drugs not received. Genotypic Resistance Data only shown for Drugs Received for Participants Meeting Confirmed Virologic Withdrawal Criteria.

  • Phenotypic Resistance Data for Drugs Received for Participants Meeting Confirmed Virologic Withdrawal Criteria [ Time Frame: Day 1 ]
    Phenotypic resistance data for drugs received for participants meeting confirmed virologic withdrawal criteria are presented below. Confirmed Virologic Withdrawal (CVW) Population consisted of all participants in the ITT-E Population who met CVW (1 CVW per arm). NA indicate that data were not applicable based on drugs were not received. Phenotypic Resistance Data only shown for Drugs Received for Participants Meeting Confirmed Virologic Withdrawal Criteria.

  • Pre-dose Concentrations of DTG and RPV at Weeks 4, 24 and 48 or Withdrawal in Participants Switching to DTG + RPV [ Time Frame: Pre-dose at Week 4, 24 and 48 or at withdrawal visit ]
    Two separate blood samples for DTG and RPV were collected pre-dose at Weeks 4, 24 and 48. Pre-dose concentrations of DTG and RPV at Weeks 4, 24 and 48 or withdrawal were summarized for the participants switching to DTG + RPV in the early switch phase. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles). Pharmacokinetic (PK) Parameter Population consisted of all participants who received DTG +RPV and provided at least one evaluable estimate of predose concentration (C0).

  • 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 Week 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. 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. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).

  • 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 (INI, NNRTI, or PI) on efficacy 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. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).

  • Changes From Baseline in Cluster Designation (CD)4+ Lymphocyte Count at Week 48 by Baseline Third Agent Treatment Class [ Time Frame: Baseline and up to Week 48 ]
    Blood for CD4 cell count assessment by flow cytometery was carried out at Baseline (Day 1), Week 4, 8, 12, 24, 36 and 48 to assess the impact of Baseline third agent class (INI, NNRTI, or PI) on efficacy, safety and tolerability of DTG +RPV compared to continuation of CAR. The full set of lymphocyte sub sets was not evaluated. Change from Baseline was calculated as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).

  • 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 (INI, NNRTI, or PI) was summarized. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).

  • 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 Week 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. Change from Baseline was calculated as value at indicated time point minus Baseline value. Number of participants who experienced maximum toxicity grade post-baseline in chemistry parameters over 48 weeks by Baseline third agent treatment class (INI, NNRTI, PI) was summarized. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).

  • 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 Week 4, 8, 12, 24, 36 and 48 to evaluate hemoglobin, hematocrit, basophils, eosinophils, lymphocytes, monocytes, neutrophils, MCV, RBC count, WBC count and platelet count. Change from Baseline was calculated as value at indicated time point minus Baseline value. 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. Participants 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; grade 4=potentially life-threatening

  • Number of Participants With Observed Genotypic Resistance for Participants Meeting Virologic Withdrawal Criteria by Baseline Third Agent Treatment Class [ Time Frame: Day 1 ]
    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.

  • Number of Participants With Observed Phenotypic Resistance for Participants Meeting Virologic Withdrawal Criteria by Baseline Third Agent Treatment Class [ Time Frame: Day 1 ]
    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.

  • Change From Baseline in Fasting Lipids at Weeks 24 and 48 by Baseline Third Agent Treatment Class [ Time Frame: Up to Week 48 ]
    Blood samples were collected at Baseline (Day 1), 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. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).

  • Change From Baseline in Pre-specified Treatment Symptoms Using the Symptom Distress Module at Weeks 4, 24 and 48 or Withdrawal From the Study [ Time Frame: Up to Week 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. Between and within treatment group comparisons were assessed on change from Baseline in pre-specified treatment symptoms using the Symptom Distress Module at Weeks 4, 24 and 48 or withdrawal from the study. Change from Baseline in Symptom count and symptom bother score have been summarized. The 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). The symptom bother score ranges from 0 to 80. Last observation carried forward (LOCF) was used as primary method of analysis. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).

  • Change From Baseline Treatment Satisfaction Using the HIV Treatment Satisfaction Questionnaire (HIV TSQ) at Weeks 4, 24 and 48 or Withdrawal From the Study [ Time Frame: Up to Week 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 0-6 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. Between and within treatment group comparisons were assessed on change from Baseline treatment satisfaction using the HIV TSQ at Weeks 4, 24 and 48 or withdrawal from the study. Total score, lifestyle/ease score and General satisfaction/clinical sub-score (CS) have been summarized. LOCF was used as primary method of analysis. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).


Enrollment: 509
Actual Study Start Date: April 14, 2015
Estimated Study Completion Date: August 12, 2021
Primary Completion Date: September 16, 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: CAR
Participants will receive CAR from Day 1 to Week 52 (Early Switch Phase), and eligible participants will switch to DTG 50 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: 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.

  Eligibility

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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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; Male condom/spermicide, male condom/diaphragm, diaphragm/spermicide; Any intrauterine device with published data showing that the expected failure rate is <1% per year; Male partner sterilization prior to the female participant's entry into the study and this male is the sole partner for that participant; Approved hormonal contraception for participants randomly assigned to DTG + RPV arm or approved hormonal contraception plus a barrier method for participants assigned to CAR; 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.

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 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 Antiretroviral therapy (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/millimeter^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, hypoalbuminaemia, 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: Subject 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 subject prior to randomization;
  • Participants who in the investigator's judgment pose a significant suicidality risk. Subject'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 subject's ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the participants;
  • 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 subject 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 subject'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
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): NCT02429791


  Show 71 Study Locations
Sponsors and Collaborators
ViiV Healthcare
Janssen Pharmaceuticals
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials ViiV Healthcare
  More Information

Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT02429791     History of Changes
Other Study ID Numbers: 201636
First Submitted: April 9, 2015
First Posted: April 29, 2015
Results First Submitted: July 27, 2017
Results First Posted: December 1, 2017
Last Update Posted: December 1, 2017
Last Verified: October 2017

Keywords provided by ViiV Healthcare:
two-drug regimen
virologically-suppressed
dolutegravir plus rilpivirine
integrase inhibitor
protease inhibitor
NNRTI-sparing
non-nucleoside reverse transcriptase inhibitor
HIV
nucleoside reverse transcriptase inhibitors

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
HIV Integrase Inhibitors
Anti-HIV Agents
Immunologic Deficiency Syndromes
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Dolutegravir
Rilpivirine
Reverse Transcriptase Inhibitors
Integrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Nucleic Acid Synthesis Inhibitors