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

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ClinicalTrials.gov Identifier: NCT04019873
Recruitment Status : Recruiting
First Posted : July 15, 2019
Last Update Posted : March 23, 2020
Sponsor:
Information provided by (Responsible Party):
ViiV Healthcare

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)

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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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

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.




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.



Information from the National Library of Medicine

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


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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

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): NCT04019873


Contacts
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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
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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
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Study Director: GSK Clinical Trials ViiV Healthcare
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Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT04019873    
Other Study ID Numbers: 207859
First Posted: July 15, 2019    Key Record Dates
Last Update Posted: March 23, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD 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

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Studies a U.S. FDA-regulated Device Product: No
Keywords provided by ViiV Healthcare:
2DR
HIV
Lamivudine
COMBINE-2
Dolutegravir
Additional relevant MeSH terms:
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HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Lamivudine
Rilpivirine
Dolutegravir
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Anti-HIV Agents
HIV Integrase Inhibitors
Integrase Inhibitors