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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:
Collaborator:
Janssen, GlaxoSmithKline (GSK)
Information provided by (Responsible Party):
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT02429791
First received: April 9, 2015
Last updated: January 16, 2017
Last verified: January 2017
  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: 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:
  • Proportion of participants with plasma HIV 1 Ribonucleic acid <50 copies/millilitre (c/mL) at Week 48. [ Time Frame: Up to Week 48. ]
    Proportion of participants having plasma HIV-1 RNA (viral load) <50 c/mL as defined by Food and Drug Administration (FDA's) Snapshot algorithm analysis will be determined to evaluate the antiviral activity following switch to DTG+RPV.


Secondary Outcome Measures:
  • Change from baseline in cluster of differentiation (CD4+) lymphocyte count at Weeks 24 and 48. [ Time Frame: Baseline, and up to Week 48. ]
    Immunological activity of DTG + RPV will be determined in terms of change in CD4+ lymphocyte count from baseline.

  • Proportion of participants with plasma HIV-1 RNA <50 c/mL at Week 24. [ Time Frame: Up to Week 24. ]
    Proportion of participants having plasma HIV-1 RNA (viral load) <50 c/mL as defined by FDA's Snapshot algorithm analysis will be determined to evaluate the antiviral activity following switch to DTG + RPV.

  • Number of participants with adverse events (AEs), Severity of AEs, and treatment discontinuations due to AEs. [ Time Frame: Up to 48 Weeks. ]
    Safety and tolerability of DTG + RPV once daily will be compared to continuation of CAR over time.

  • Changes in laboratory parameter abnormalities. [ Time Frame: Up to 48 Weeks. ]
    Safety and tolerability of DTG + RPV once daily compared to continuation of CAR over 48 weeks.

  • Change from baseline in renal, bone, and cardiovascular biomarkers. [ Time Frame: Baseline, and Week 48. ]
    Safety will be assessed in terms of biomarkers at Week 48. Blood sample will be collected for renal, bone, and cardiovascular biomarker assessments. Urine sample will be collected for renal biomarker assessments.

  • Change from baseline in fasting lipids. [ Time Frame: Baseline, and up to Week 48. ]
    Safety will be assessed in terms of fasting lipid levels at Weeks 24 and 48. Effects of DTG +RPV on fasting lipids will be compared to continuation of CAR.

  • Incidence of observed genotypic and phenotypic resistance to CAR and to DTG or RPV for participants meeting Virologic Withdrawal Criteria [ Time Frame: 148 weeks. ]
    Blood samples will be obtained for viral genotypic and phenotypic analyses.

  • Pre-dose concentrations of DTG and RPV. [ Time Frame: Pre-dose blood samples will be collected on Weeks 4, 24, 48, 56, 76, 100 (or at withdrawal visit) for participants switching to DTG + RPV. ]
    DTG and RPV trough concentrations will be determined in subjects switching to DTG + RPV.

  • Pre-dose concentrations of DTG and RPV in the first 20 participants who switch from efavirenz (EVF) or nevirapine (NVP) to DTG +RPV. [ Time Frame: Pre-dose blood samples will be collected on Weeks 2, 4 and 8 for analysis of DTG and RPV PK. ]
    DTG and RPV trough concentrations over time will be assessed for subjects who switch from EFV or NVP to DTG + RPV.

  • Proportion of participants with plasma HIV-1 RNA <50 c/mL in subgroups stratified based on baseline third agent treatment class. [ Time Frame: Up to Week 48. ]
    Impact of baseline third agent treatment class (INI, NNRTI, or PI) on antiviral activity of DTG + RPV once daily compared to continuation of CAR will be assessed.

  • Change from baseline to Week 48 in CD4+ lymphocyte counts in subgroups stratified based on baseline third agent treatment class. [ Time Frame: Baseline, and up to Week 48. ]
    Impact of baseline third agent treatment class (INI, NNRTI, or PI) on immunological activity of DTG + RPV once daily compared to continuation of CAR will be assessed.

  • Number of participants with AEs, severity of AEs, and treatment discontinuations due to AEs, in subgroups stratified based on baseline third agent treatment class. [ Time Frame: Up to 48 weeks. ]
    Impact of baseline third agent treatment class (INI, NNRTI, or PI) on clinical efficacy safety and tolerability of DTG + RPV once daily will be compared to continuation of CAR over time.

  • Changes in laboratory parameter abnormalities in subgroups stratified based on baseline third agent treatment class. [ Time Frame: Up to 48 weeks. ]
    Impact of baseline third agent treatment class (INI, NNRTI, or PI) on safety and tolerability of DTG + RPV once daily will be compared to continuation of CAR over time.

  • Incidence of observed genotypic and phenotypic resistance to CAR and to DTG or RPV for participants meeting Virologic Withdrawal Criteria in subgroups stratified based on baseline third agent treatment class (INI, NNRTI, or PI). [ Time Frame: 148 weeks. ]
    Blood samples will be obtained for viral genotypic and phenotypic analyses from subjects meeting suspected Virologic Withdrawal Criteria.

  • Change from baseline in fasting lipids in subgroups stratified based on baseline third agent treatment class (INI, NNRTI, or PI). [ Time Frame: Baseline, and up to Week 48. ]
    Safety will be assessed in terms of fasting lipid levels at Weeks 24 and 48.

  • Change from baseline in pre-specified treatment symptoms and in treatment satisfaction. [ Time Frame: Baseline and up to Week 148 (or withdrawal from study). ]
    Change from baseline in pre-specified treatment symptoms (using the Symptom Distress Module) at Weeks 4, 24, 48, 56, 76, 100 and 148. Change from baseline in treatment satisfaction will be assessed using HIV treatment satisfaction questionnaire (HIV TSQ) at Weeks 4, 24, 48, 56, 76, 100 and 148.


Enrollment: 510
Study Start Date: April 2015
Estimated Study Completion Date: August 2021
Primary Completion Date: September 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

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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02429791

  Show 71 Study Locations
Sponsors and Collaborators
ViiV Healthcare
Janssen, GlaxoSmithKline (GSK)
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
Study First Received: April 9, 2015
Last Updated: January 16, 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
Anti-HIV Agents
HIV Integrase Inhibitors
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
Rilpivirine
Reverse Transcriptase Inhibitors
Dolutegravir
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Integrase Inhibitors

ClinicalTrials.gov processed this record on April 28, 2017