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History of Changes for Study: NCT02422797
Regimen Switch to Dolutegravir + Rilpivirine From Current Antiretroviral Regimen in Human Immunodeficiency Virus Type 1 Infected and Virologically Suppressed Adults (SWORD-2)
Latest version (submitted December 3, 2021) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 April 20, 2015 None (earliest Version on record)
2 April 23, 2015 Outcome Measures, Contacts/Locations and Study Status
3 January 25, 2016 Recruitment Status, Study Status, Contacts/Locations, Outcome Measures, Eligibility, Arms and Interventions and Study Design
4 February 4, 2016 Study Status
5 February 25, 2016 Study Status
6 May 12, 2016 Study Status
7 June 9, 2016 Study Status
8 July 5, 2016 Study Status
9 September 15, 2016 Study Status
10 June 8, 2017 Study Status, Contacts/Locations, Sponsor/Collaborators, Study Design, Oversight
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Results Submission Events
11 September 22, 2017 Outcome Measures, Study Status, Results and Contacts/Locations
12 November 6, 2017 Contacts/Locations and Study Status
13 December 14, 2017 Study Status
14 February 1, 2018 Study Status
15 June 21, 2018 Study Status
16 June 28, 2018 Study Status
17 July 23, 2018 Study Status
18 August 6, 2018 Study Status
19 August 16, 2018 Study Status
20 October 15, 2018 Arms and Interventions, Study Status, IPDSharing, Eligibility, Conditions and Study Identification
21 July 23, 2019 IPDSharing, Contacts/Locations, Study Status, References and Study Identification
22 October 31, 2019 Adverse Events, Outcome Measures, Participant Flow, Baseline Characteristics, Study Status and More Information
23 February 12, 2020 Study Status
24 February 28, 2020 Study Status
25 April 10, 2020 Study Status
26 April 15, 2020 Study Status
27 June 9, 2020 Study Status
28 August 20, 2020 Study Status
29 September 24, 2020 Study Status and Participant Flow
30 August 27, 2021 Study Status
31 October 25, 2021 Study Status
32 December 3, 2021 Study Status
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Study NCT02422797
Submitted Date:  April 20, 2015 (v1)

Open or close this module Study Identification
Unique Protocol ID: 201637
Brief Title: Regimen Switch to Dolutegravir + Rilpivirine From Current Antiretroviral Regimen in Human Immunodeficiency Virus Type 1 Infected and Virologically Suppressed Adults (SWORD-2)
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-2)
Secondary IDs:
Open or close this module Study Status
Record Verification: April 2015
Overall Status: Not yet recruiting
Study Start: April 2015
Primary Completion: August 2021 [Anticipated]
Study Completion: August 2021 [Anticipated]
First Submitted: April 9, 2015
First Submitted that
Met QC Criteria:
April 20, 2015
First Posted: April 21, 2015 [Estimate]
Last Update Submitted that
Met QC Criteria:
April 20, 2015
Last Update Posted: April 21, 2015 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: ViiV Healthcare
Responsible Party: Sponsor
Collaborators: Janssen/GlaxoSmithKline
GlaxoSmithKline
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: Yes
Open or close this module Study Description
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.
Detailed Description:
Open or close this module Conditions
Conditions: Infection, Human Immunodeficiency Virus
Keywords: HIV
protease inhibitor
non-nucleoside reverse transcriptase inhibitor
NNRTI-sparing
integrase inhibitor
two-drug regimen
dolutegravir plus rilpivirine
nucleoside reverse transcriptase inhibitors
virologically-suppressed
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 3
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: None (Open Label)
Allocation: Randomized
Enrollment: 476 [Anticipated]
Open or close this module Arms and Interventions
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 1through 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.
Open or close this module Outcome Measures
Primary Outcome Measures:
1. 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:
1. 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.
2. 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.
3. 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 48 weeks.
4. Changes in laboratory parameter abnormalities (composite)
[ Time Frame: Up to 48 Weeks. ]

5. 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 also be collected for renal biomarker assessments.
6. 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.
7. 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.
8. 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.
9. Pre-dose concentrations of DTG and RPV in first 20 participants from NNRTI subset who switch from efavirenz (EFV) or nevirapine (NVP) to DTG +RPV.
[ Time Frame: Pre-dose blood samples will be collected on Weeks 2, and 8 for analysis of DTG and RPV PK and analysis of EFV or NVP PK at Week 2, if indicated. ]

Impact of residual enzyme induction effects of NNRTIs on DTG and RPV trough concentrations will be assessed.
10. 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 compared to continuation of CAR will be assessed.
11. 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 compared to continuation of CAR will be assessed.
12. 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.
13. Changes laboratory parameters abnormalities in subgroups stratified based on baseline third agent treatment class. (composite)
[ 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.
14. 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.
15. 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.
16. 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.
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
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 to a second cART regimen, 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) (must be initial cART regimen; one within PI class switch permitted for tolerability).

  • 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 investigational product (IP), 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 IP 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 for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (anti-HBc), and antibodies against Hepatitis B surface antigen (anti-HBsAg) as follows: Participants positive for HBsAg are excluded; Participants positive for anti-HBc (negative HBsAg status) and negative for anti HBsAg are 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 (including substance abuse disorder) 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 the first dose of investigational product.
  • 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 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 must be provided to GlaxoSmithKline, after screening and before randomization, to provide direct evidence of no pre-existing major resistance mutations. You must wait for the study virologists to confirm the lack of major 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).
Open or close this module Contacts/Locations
Central Contact Person: US GSK Clinical Trials Call Center
Telephone: 877-379-3718
Email: GSKClinicalSupportHD@gsk.com
Study Officials: GSK Clinical Trials
Study Director
ViiV Healthcare
Locations:
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Links:
Available IPD/Information:

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