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出境医 / 临床实验 / 'COMBINE-2': Real-world Evidence for Effectiveness of Two Drug Regimen, Antiretroviral Therapy With Integrase Inhibitors Plus a Reverse Transcriptase Inhibitor

'COMBINE-2': Real-world Evidence for Effectiveness of Two Drug Regimen, Antiretroviral Therapy With Integrase Inhibitors Plus a Reverse Transcriptase Inhibitor

Study Description
Brief Summary:
Dolutegravir (DTG) is a well-tolerated 2nd generation integrase strand transfer inhibitor (INSTI); rilpivirine (RPV) is a well-tolerated non- nucleoside reverse transcriptase inhibitors (NNRTI) and lamivudine (3TC) is a nucleoside reverse transcriptase inhibitors (NRTIs). This study aims to gather the real-world evidence to evaluate effectiveness of the two-drug regimen (2DR). This is a multi-site observational study in subjects who have started and/or who plan to initiate 2DR with an integrase inhibitor plus a reverse transcriptase inhibitor. The study does not require any changes to the routine standard of care that subjects receive. Approximately 500 eligible subjects will be included from potential investigational sites across Europe and data from them will be collected either retrospectively or prospectively.

Condition or disease Intervention/treatment
HIV Infections Drug: Dolutegravir (DTG) Drug: Lamivudine (3TC) Drug: Rilpivirine (RPV)

Study Design
Layout table for study information
Study Type : Observational
Estimated Enrollment : 1 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: 'COMBINE-2': Real-world Evidence for Effectiveness of Two Drug Regimen, Antiretroviral Therapy With Integrase Inhibitors Plus a Reverse Transcriptase Inhibitor
Actual Study Start Date : November 18, 2019
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2021
Arms and Interventions
Group/Cohort Intervention/treatment
Subjects receiving 2DR treatment
Data will be collected from HIV positive male or female adult subjects who have started 2DR with an integrase inhibitor plus a reverse transcriptase inhibitor from 2014.
 Drug: Dolutegravir (DTG)
DTG is a 2nd generation integrase strand transfer inhibitor. Subjects receiving DTG as a part of 2DR treatment will be included in the study.

Drug: Lamivudine (3TC)
3TC is a nucleoside reverse transcriptase inhibitor. Subjects receiving 3TC as a part of 2DR treatment will be included in the study.

Drug: Rilpivirine (RPV)
RPV is a non-nucleoside reverse transcriptase inhibitor. Subjects receiving RPV as part of 2DR treatment will be included in the study.
Outcome Measures
Primary Outcome Measures :
  1. Number of treatment-naïve subjects with human immunodeficiency virus ribonucleic acid (HIV-RNA) levels <50 copies/milliliter (c/mL) at Week 24 [ Time Frame: Week 24 ]
    Number of treatment-naïve subjects with human immunodeficiency virus ribonucleic acid (HIV-RNA) levels <50 c/mL at Week 24 will be assessed.

  2. Number of treatment-naïve subjects with human immunodeficiency virus ribonucleic acid (HIV-RNA) levels <50 c/mL at Week 48 [ Time Frame: Week 48 ]
    Number of treatment-naïve subjects with human immunodeficiency virus ribonucleic acid (HIV-RNA) levels <50 c/mL at Week 48 will be assessed.

  3. Number of treatment-naïve subjects with human immunodeficiency virus ribonucleic acid (HIV-RNA) levels <50 c/mL at Week 96 [ Time Frame: Week 96 ]
    Number of treatment-naïve subjects with human immunodeficiency virus ribonucleic acid (HIV-RNA) levels <50 c/mL at Week 96 will be assessed.

  4. Number of subjects who lose virologic control within the first 24 weeks after switching to a 2-DR [ Time Frame: Week 24 ]
    Virologic control is defined as 2 consecutive HIV RNA levels >50 c/mL or HIV RNA >50c/mL followed by study treatment discontinuation or missing value. Number of subjects who lose virologic control will be assessed using a Kaplan-Meier Method.

  5. Number of subjects who lose virologic control within the first 48 weeks after switching to a 2-DR [ Time Frame: Week 48 ]
    Virologic control is defined as 2 consecutive HIV RNA levels >50 c/mL or HIV RNA >50c/mL followed by study treatment discontinuation or missing value. Number of subjects who lose virologic control will be assessed using a Kaplan-Meier Method.

  6. Number of subjects who lose virologic control within the first 96 weeks after switching to a 2-DR [ Time Frame: Week 96 ]
    Virologic control is defined as 2 consecutive HIV RNA levels >50 c/mL or HIV RNA >50c/mL followed by study treatment discontinuation or missing value. Number of subjects who lose virologic control will be assessed using a Kaplan-Meier Method.

  7. Number of treatment-experienced subjects with HIV-RNA levels <50 c/mL at Week 24 [ Time Frame: Week 24 ]
    Number of treatment-experienced subjects with HIV-RNA levels <50 c/mL at Week 24 will be assessed.

  8. Number of treatment-experienced subjects with HIV-RNA levels <50 c/mL at Week 48 [ Time Frame: Week 48 ]
    Number of treatment-experienced subjects with HIV-RNA levels <50 c/mL at Week 48 will be assessed.

  9. Number of treatment-experienced subjects with HIV-RNA levels <50 c/mL at Week 96 [ Time Frame: Week 96 ]
    Number of treatment-experienced subjects with HIV-RNA levels <50 c/mL at Week 96 will be assessed.


Secondary Outcome Measures :
  1. Number of subjects with HIV RNA >200 c/mL after 24 weeks [ Time Frame: Week 24 ]
    Subjects will be assessed for HIV RNA >200 c/mL after Week 24.

  2. Number of subjects with HIV RNA >200 c/mL after 48 weeks [ Time Frame: Week 48 ]
    Subjects will be assessed for HIV RNA >200 c/mL after Week 48.

  3. Number of subjects with HIV RNA >200 c/mL after 96 weeks [ Time Frame: Week 96 ]
    Subjects will be assessed for HIV RNA >200 c/mL after Week 96.

  4. Number of subjects with low level viremia [ Time Frame: Up to Week 96 ]
    Low level viremia is defined as virologic load >50 and <200 c/mL. Number of subjects with low level viremia will be assessed at indicated time points.

  5. Time to virologic suppression [ Time Frame: Up to Week 96 ]
    Virologic suppression is defined as viral load < 50 c/mL at the end of 6months/12months/18 months or as pre-specified.

  6. Time to virologic failure [ Time Frame: Up to Week 96 ]
    Time to virologic failure in the stable switch Population will be assessed. Subjects with virologic rebound or virologic non-response will be considered as failure.

  7. Number of subjects with resistance profile in case of virologic failure [ Time Frame: Up to Week 96 ]
    Subjects with virologic rebound or virologic non-response will be considered as failure. Results of all HIV resistance tests performed before and during antiretroviral treatment will be evaluated to analyze resistance profile in case of virologic failure.

  8. Number of subjects with stable switch while virologically suppressed [ Time Frame: Up to Week 96 ]
    A switching option for those with HIV RNA suppression on current treatment will be called as 'Stable switch'. Number of subjects with stable switch while virologically suppressed will be analyzed.

  9. Number of subjects with Switch after Failure [ Time Frame: Up to Week 96 ]
    Subjects with virologic rebound or virologic non-response will be considered as failure. Number of subjects with Switch after Failure will be analyzed.

  10. Number of subjects switching for safety reasons [ Time Frame: Up to Week 96 ]
    Number of subjects switching for safety reasons including tolerability, toxicity and other reasons will be evaluated.

  11. Number of subjects with adverse events (AEs) and serious AEs (SAEs) [ Time Frame: Up to Week 96 ]
    An AE is any untoward medical occurrence in a subject, 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 or any other situation according to medical or scientific judgment will be categorized as SAE.

  12. cluster of differentiation (CD)4+ and CD8+ T cell counts [ Time Frame: Up to Week 96 ]
    All available CD4 and CD8 results since first starting 2DR treatment will be collected to analyze CD4+ and CD8+ T cell counts.

  13. CD4/CD8 ratio at each time point [ Time Frame: Up to Week 96 ]
    All available CD4 and CD8 results since first starting 2DR treatment will be collected to analyze CD4/CD8 ratio at each time point

  14. Number of factors associated with plasma HIV-RNA > 50 c/mL [ Time Frame: Up to Week 96 ]
    If number of failure allows, analysis to assess factors associated with success at week 96 in naïve and treatment experienced populations and with virologic failure in population switching with HIV RNA suppression will be analyzed.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Sampling Method:   Non-Probability Sample
Study Population
The study population will consist of HIV positive male or female subjects aged 18 years or over and who have started 2DR with an integrase inhibitor plus a reverse transcriptase inhibitor from 2014 onwards as a first-line treatment among naïve subjects, or a switching option for those with HIV RNA suppression on current treatment (stable switches), or a second-line treatment for those with virological failure on prior treatment.
Criteria

Inclusion Criteria:

  • HIV positive male or female subjects aged 18 years or over and who have started 2DR with an integrase inhibitor plus a reverse transcriptase inhibitor from 2014 onwards as a first-line treatment among naïve subjects, or a switching option for those with HIV RNA suppression on current treatment (stable switches), or a second-line treatment for those with virological failure on prior treatment.

Exclusion Criteria:

  • No specific exclusion criteria
Contacts and Locations

Contacts
Layout table for location contacts
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com

Locations
Layout table for location information
Spain
GSK Investigational Site Recruiting
Barcelona, Spain, 08041
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Marta Gutiérrez         
Sponsors and Collaborators
ViiV Healthcare
Investigators
Layout table for investigator information
Study Director: GSK Clinical Trials ViiV Healthcare
Tracking Information
First Submitted Date July 19, 2018
First Posted Date July 15, 2019
Last Update Posted Date March 23, 2020
Actual Study Start Date November 18, 2019
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: July 12, 2019)
  • Number of treatment-naïve subjects with human immunodeficiency virus ribonucleic acid (HIV-RNA) levels <50 copies/milliliter (c/mL) at Week 24 [ Time Frame: Week 24 ]
    Number of treatment-naïve subjects with human immunodeficiency virus ribonucleic acid (HIV-RNA) levels <50 c/mL at Week 24 will be assessed.
  • Number of treatment-naïve subjects with human immunodeficiency virus ribonucleic acid (HIV-RNA) levels <50 c/mL at Week 48 [ Time Frame: Week 48 ]
    Number of treatment-naïve subjects with human immunodeficiency virus ribonucleic acid (HIV-RNA) levels <50 c/mL at Week 48 will be assessed.
  • Number of treatment-naïve subjects with human immunodeficiency virus ribonucleic acid (HIV-RNA) levels <50 c/mL at Week 96 [ Time Frame: Week 96 ]
    Number of treatment-naïve subjects with human immunodeficiency virus ribonucleic acid (HIV-RNA) levels <50 c/mL at Week 96 will be assessed.
  • Number of subjects who lose virologic control within the first 24 weeks after switching to a 2-DR [ Time Frame: Week 24 ]
    Virologic control is defined as 2 consecutive HIV RNA levels >50 c/mL or HIV RNA >50c/mL followed by study treatment discontinuation or missing value. Number of subjects who lose virologic control will be assessed using a Kaplan-Meier Method.
  • Number of subjects who lose virologic control within the first 48 weeks after switching to a 2-DR [ Time Frame: Week 48 ]
    Virologic control is defined as 2 consecutive HIV RNA levels >50 c/mL or HIV RNA >50c/mL followed by study treatment discontinuation or missing value. Number of subjects who lose virologic control will be assessed using a Kaplan-Meier Method.
  • Number of subjects who lose virologic control within the first 96 weeks after switching to a 2-DR [ Time Frame: Week 96 ]
    Virologic control is defined as 2 consecutive HIV RNA levels >50 c/mL or HIV RNA >50c/mL followed by study treatment discontinuation or missing value. Number of subjects who lose virologic control will be assessed using a Kaplan-Meier Method.
  • Number of treatment-experienced subjects with HIV-RNA levels <50 c/mL at Week 24 [ Time Frame: Week 24 ]
    Number of treatment-experienced subjects with HIV-RNA levels <50 c/mL at Week 24 will be assessed.
  • Number of treatment-experienced subjects with HIV-RNA levels <50 c/mL at Week 48 [ Time Frame: Week 48 ]
    Number of treatment-experienced subjects with HIV-RNA levels <50 c/mL at Week 48 will be assessed.
  • Number of treatment-experienced subjects with HIV-RNA levels <50 c/mL at Week 96 [ Time Frame: Week 96 ]
    Number of treatment-experienced subjects with HIV-RNA levels <50 c/mL at Week 96 will be assessed.
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: July 12, 2019)
  • Number of subjects with HIV RNA >200 c/mL after 24 weeks [ Time Frame: Week 24 ]
    Subjects will be assessed for HIV RNA >200 c/mL after Week 24.
  • Number of subjects with HIV RNA >200 c/mL after 48 weeks [ Time Frame: Week 48 ]
    Subjects will be assessed for HIV RNA >200 c/mL after Week 48.
  • Number of subjects with HIV RNA >200 c/mL after 96 weeks [ Time Frame: Week 96 ]
    Subjects will be assessed for HIV RNA >200 c/mL after Week 96.
  • Number of subjects with low level viremia [ Time Frame: Up to Week 96 ]
    Low level viremia is defined as virologic load >50 and <200 c/mL. Number of subjects with low level viremia will be assessed at indicated time points.
  • Time to virologic suppression [ Time Frame: Up to Week 96 ]
    Virologic suppression is defined as viral load < 50 c/mL at the end of 6months/12months/18 months or as pre-specified.
  • Time to virologic failure [ Time Frame: Up to Week 96 ]
    Time to virologic failure in the stable switch Population will be assessed. Subjects with virologic rebound or virologic non-response will be considered as failure.
  • Number of subjects with resistance profile in case of virologic failure [ Time Frame: Up to Week 96 ]
    Subjects with virologic rebound or virologic non-response will be considered as failure. Results of all HIV resistance tests performed before and during antiretroviral treatment will be evaluated to analyze resistance profile in case of virologic failure.
  • Number of subjects with stable switch while virologically suppressed [ Time Frame: Up to Week 96 ]
    A switching option for those with HIV RNA suppression on current treatment will be called as 'Stable switch'. Number of subjects with stable switch while virologically suppressed will be analyzed.
  • Number of subjects with Switch after Failure [ Time Frame: Up to Week 96 ]
    Subjects with virologic rebound or virologic non-response will be considered as failure. Number of subjects with Switch after Failure will be analyzed.
  • Number of subjects switching for safety reasons [ Time Frame: Up to Week 96 ]
    Number of subjects switching for safety reasons including tolerability, toxicity and other reasons will be evaluated.
  • Number of subjects with adverse events (AEs) and serious AEs (SAEs) [ Time Frame: Up to Week 96 ]
    An AE is any untoward medical occurrence in a subject, 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 or any other situation according to medical or scientific judgment will be categorized as SAE.
  • cluster of differentiation (CD)4+ and CD8+ T cell counts [ Time Frame: Up to Week 96 ]
    All available CD4 and CD8 results since first starting 2DR treatment will be collected to analyze CD4+ and CD8+ T cell counts.
  • CD4/CD8 ratio at each time point [ Time Frame: Up to Week 96 ]
    All available CD4 and CD8 results since first starting 2DR treatment will be collected to analyze CD4/CD8 ratio at each time point
  • Number of factors associated with plasma HIV-RNA > 50 c/mL [ Time Frame: Up to Week 96 ]
    If number of failure allows, analysis to assess factors associated with success at week 96 in naïve and treatment experienced populations and with virologic failure in population switching with HIV RNA suppression will be analyzed.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title 'COMBINE-2': Real-world Evidence for Effectiveness of Two Drug Regimen, Antiretroviral Therapy With Integrase Inhibitors Plus a Reverse Transcriptase Inhibitor
Official Title 'COMBINE-2': Real-world Evidence for Effectiveness of Two Drug Regimen, Antiretroviral Therapy With Integrase Inhibitors Plus a Reverse Transcriptase Inhibitor
Brief Summary Dolutegravir (DTG) is a well-tolerated 2nd generation integrase strand transfer inhibitor (INSTI); rilpivirine (RPV) is a well-tolerated non- nucleoside reverse transcriptase inhibitors (NNRTI) and lamivudine (3TC) is a nucleoside reverse transcriptase inhibitors (NRTIs). This study aims to gather the real-world evidence to evaluate effectiveness of the two-drug regimen (2DR). This is a multi-site observational study in subjects who have started and/or who plan to initiate 2DR with an integrase inhibitor plus a reverse transcriptase inhibitor. The study does not require any changes to the routine standard of care that subjects receive. Approximately 500 eligible subjects will be included from potential investigational sites across Europe and data from them will be collected either retrospectively or prospectively.
Detailed Description Not Provided
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population The study population will consist of HIV positive male or female subjects aged 18 years or over and who have started 2DR with an integrase inhibitor plus a reverse transcriptase inhibitor from 2014 onwards as a first-line treatment among naïve subjects, or a switching option for those with HIV RNA suppression on current treatment (stable switches), or a second-line treatment for those with virological failure on prior treatment.
Condition HIV Infections
Intervention
  • Drug: Dolutegravir (DTG)
    DTG is a 2nd generation integrase strand transfer inhibitor. Subjects receiving DTG as a part of 2DR treatment will be included in the study.
  • Drug: Lamivudine (3TC)
    3TC is a nucleoside reverse transcriptase inhibitor. Subjects receiving 3TC as a part of 2DR treatment will be included in the study.
  • Drug: Rilpivirine (RPV)
    RPV is a non-nucleoside reverse transcriptase inhibitor. Subjects receiving RPV as part of 2DR treatment will be included in the study.
Study Groups/Cohorts Subjects receiving 2DR treatment
Data will be collected from HIV positive male or female adult subjects who have started 2DR with an integrase inhibitor plus a reverse transcriptase inhibitor from 2014.
Interventions:
  • Drug: Dolutegravir (DTG)
  • Drug: Lamivudine (3TC)
  • Drug: Rilpivirine (RPV)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: July 12, 2019) 		1
Original Estimated Enrollment Same as current
Estimated Study Completion Date December 31, 2021
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • HIV positive male or female subjects aged 18 years or over and who have started 2DR with an integrase inhibitor plus a reverse transcriptase inhibitor from 2014 onwards as a first-line treatment among naïve subjects, or a switching option for those with HIV RNA suppression on current treatment (stable switches), or a second-line treatment for those with virological failure on prior treatment.

Exclusion Criteria:

  • No specific exclusion criteria
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers Not Provided
Contacts
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com
Listed Location Countries Spain
Removed Location Countries  
 
Administrative Information
NCT Number NCT04019873
Other Study ID Numbers 207859
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Device Product: No
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
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
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: http://clinicalstudydatarequest.com
Responsible Party ViiV Healthcare
Study Sponsor ViiV Healthcare
Collaborators Not Provided
Investigators
Study Director: GSK Clinical Trials ViiV Healthcare
PRS Account ViiV Healthcare
Verification Date March 2020

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