Study to Evaluate Efficacy and Safety of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) Regimen Versus Boosted Protease Inhibitor (bPI) Along With Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) Regimen in Virologically-Suppressed, HIV-1 Infected Participants

NCT02269917 | Completed Phase 3 Results DMC

• 3 other identifiers: CR105736TMC114IFD30132014-003052-31
• Study Type: interventional
• Target: 1,149
• Locations: 10 countries
• Sites: 79

Brief Summary

The purpose of this study is to demonstrate non-inferiority in efficacy while switching to a once-daily single-tablet regimen containing darunavir (DRV)/ cobicistat (COBI)/ emtricitabine (FTC)/ tenofovir alafenamide (TAF) (D/C/F/TAF tablet) relative to continuing the current regimen consisting of a boosted protease inhibitor (bPI) combined with tenofovir disoproxil fumarate (FTC/TDF) in virologically-suppressed (human immunodeficiency virus type 1 ribonucleic acid \[HIV-1 RNA\] concentrations less than \[\<\] 50 copies per milliliter \[copies/mL\]) HIV-1 infected participants.

Conditions

Human Immunodeficiency Virus Type 1

Keywords

Human Immunodeficiency Virus Type 1; Emerald; Darunavir; Cobicistat; Emtricitabine; Tenofovir Alafenamide

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Virologic Rebound (HIV-1 RNA >=50 Copies/mL) Cumulative Through Week 48

  Virologic rebound was defined as: confirmed plasma human immunodeficiency virus - 1 (HIV-1) Ribonucleic Acid (RNA) level greater than or equal to (\>=)50 copies per milliliter (copies/mL) up to, and including the upper bound of the Week 48 window (ie, 54 weeks) and last available on-treatment (single) HIV-1 RNA \>=50 copies/mL at premature discontinuation (irrespective of reason). Percentage of participants with virologic rebound were reported.

  Through Week 48

Secondary Outcomes (56)

• Percentage of Participants With Virologic Rebound (Plasma HIV-1 RNA >=20 Copies/mL) Cumulative Through 48 Weeks

  Through 48 Weeks

• Percentage of Participants With Virologic Rebound (Plasma HIV-1 RNA >=200 Copies/mL) Cumulative Through 48 Weeks

  Through 48 Weeks

• Percentage of Participants With Non-Virologic Rebound at Week 48 by Kaplan-Meier Estimates

  Baseline up to Week 48

• Percentage of Participants Experiencing Grade 3 and 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and Premature Discontinuation Due to AEs Through Week 48

  Up to Week 48

• Change From Baseline in Serum Creatinine Levels at Weeks 24 and 48

  Baseline and Weeks 24 and 48

Study Arms (2)

Experimental Treatment Regimen

EXPERIMENTAL

Participants will receive a single fixed dose combination (FDC) tablet containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF tablet), orally once daily, up to Week 48. After Week 48, all participants will continue to receive the D/C/F/TAF tablet in a 48 week extension phase (up to Week 96).

Drug: D/C/F/TAF

Current Treatment Regimen

ACTIVE COMPARATOR

Participants will receive a boosted protease inhibitor (bPI) (limited to darunavir \[DRV\] or atazanavir with low-dose ritonavir \[rtv\] or cobicistat \[COBI\], or lopinavir with rtv) combined with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) up to Week 52. After Week 52, all participants will receive the D/C/F/TAF tablet in a 44 week extension phase (up to Week 96).

Drug: Boosted Protease Inhibitor (bPI); Drug: FTC/TDF

Interventions

D/C/F/TAF DRUG

Once-daily single-tablet regimen containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg.

Experimental Treatment Regimen

Boosted Protease Inhibitor (bPI) DRUG

Boosted protease inhibitor (limited to darunavir \[DRV\] or atazanavir with low-dose ritonavir \[rtv\] or cobicistat \[COBI\], or lopinavir with rtv) as per current treatment regimen.

Current Treatment Regimen

FTC/TDF DRUG

Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF).

Current Treatment Regimen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Currently being treated with a stable antiretroviral (ARV) regimen consisting of a boosted protease inhibitor (limited to darunavir \[DRV\] or atazanavir with low-dose ritonavir \[rtv\] or cobicistat \[COBI\], or lopinavir with rtv) combined with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) only, for at least 6 consecutive months preceding the Screening visit
• On-treatment plasma human immunodeficiency virus type 1 ribonucleic acid (HIV-1 RNA) concentrations less than (\<) 50 copies per milliliter (copies/mL) or HIV-1 RNA undetectable by a local HIV-1 RNA test between 12 and 2 months prior to the Screening visit and have HIV-1 RNA \<50 copies/mL at the Screening visit
• A single virologic elevation of greater than or equal to (\>=) 50 copies/mL after previously reaching viral suppression between 12 and 2 months prior to Screening is acceptable, provided a subsequent test prior to Screening was \<50 copies/mL
• Absence of history of failure on DRV treatment and absence of DRV resistance-associated mutations (RAMs), if documented historical genotypes are available
• Normal electrocardiogram (ECG) at Screening (or if abnormal, determined by the Investigator to be not clinically significant)

You may not qualify if:

• A new acquired immunodeficiency syndrome (AIDS) - defining condition diagnosed within the 30 days prior to Screening
• Proven or suspected acute hepatitis within 30 days prior to study entry
• Hepatitis C antibody positive; however, participants previously cured of hepatitis C virus (HCV) infection, with documented sustained virologic response, that is, undetectable HCV RNA 24 weeks after the last dose of HCV treatment, are allowed to participate
• Hepatitis B surface antigen (HBsAg) positive
• Participants with cirrhosis as diagnosed based on local practices

Sponsors & Collaborators

• Janssen R&D Ireland: lead

Study Sites (79)

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Phoenix, Arizona, United States

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Bakersfield, California, United States

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Beverly Hills, California, United States

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Long Beach, California, United States

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Los Angeles, California, United States

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San Diego, California, United States

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San Francisco, California, United States

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Washington D.C., District of Columbia, United States

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Fort Lauderdale, Florida, United States

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Ft. Pierce, Florida, United States

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Orlando, Florida, United States

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West Palm Beach, Florida, United States

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Atlanta, Georgia, United States

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Savannah, Georgia, United States

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Chicago, Illinois, United States

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Boston, Massachusetts, United States

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Springfield, Massachusetts, United States

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Berkley, Michigan, United States

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Detroit, Michigan, United States

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Minneapolis, Minnesota, United States

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Kansas City, Missouri, United States

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St Louis, Missouri, United States

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Hillsborough, New Jersey, United States

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Newark, New Jersey, United States

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Somers Point, New Jersey, United States

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Santa Fe, New Mexico, United States

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New York, New York, United States

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Chapel Hill, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Cincinnati, Ohio, United States

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Philadelphia, Pennsylvania, United States

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Providence, Rhode Island, United States

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Austin, Texas, United States

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Dallas, Texas, United States

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Fort Worth, Texas, United States

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Houston, Texas, United States

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Longview, Texas, United States

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Seattle, Washington, United States

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Antwerp, Belgium

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Brussels, Belgium

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Ghent, Belgium

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Leuven, Belgium

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Liège, Belgium

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Edmonton, Alberta, Canada

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Vancouver, British Columbia, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Le Kremlin-Bicêtre, France

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Lyon, France

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Marseille, France

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Montpellier, France

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Nantes, France

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Paris, France

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Strasbourg, France

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Tourcoing, France

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Bydgoszcz, Poland

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Chorzów, Poland

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Lodz, Poland

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Warsaw, Poland

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Wroclaw, Poland

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San Juan, Puerto Rico

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Alicante, Spain

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Badalona, Spain

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Barcelona, Spain

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Córdoba, Spain

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Donostia / San Sebastian, Spain

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Elche, Spain

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Madrid, Spain

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Seville, Spain

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Valencia, Spain

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Gothenburg, Sweden

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Malmo, Sweden

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Stockholm, Sweden

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Basel, Switzerland

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Bern, Switzerland

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Zurich, Switzerland

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Brighton, United Kingdom

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London, United Kingdom

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Manchester, United Kingdom

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Related Publications (5)

• Ackaert O, McDougall D, Perez-Ruixo C, Perez-Ruixo JJ, Jezorwski J, Crauwels HM. Population Pharmacokinetic Analysis of Darunavir and Tenofovir Alafenamide in HIV-1-Infected Patients on the Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Single-Tablet Regimen (AMBER and EMERALD Studies). AAPS J. 2021 Jun 7;23(4):82. doi: 10.1208/s12248-021-00607-8.

  PMID: 34100149 DERIVED

• Huhn GD, Wilkin A, Mussini C, Spinner CD, Jezorwski J, El Ghazi M, Van Landuyt E, Lathouwers E, Brown K, Baugh B; AMBER and EMERALD study groups. Week 96 subgroup analyses of the phase 3, randomized AMBER and EMERALD trials evaluating the efficacy and safety of the once daily darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) single-tablet regimen in antiretroviral treatment (ART)-naive and -experienced, virologically-suppressed adults living with HIV-1. HIV Res Clin Pract. 2020 Dec;21(6):151-167. doi: 10.1080/25787489.2020.1844520. Epub 2021 Feb 2.

  PMID: 33528318 DERIVED

• Lathouwers E, Wong EY, Brown K, Baugh B, Ghys A, Jezorwski J, Mohsine EG, Van Landuyt E, Opsomer M, De Meyer S; AMBER and EMERALD Study Groups. Week 48 Resistance Analyses of the Once-Daily, Single-Tablet Regimen Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) in Adults Living with HIV-1 from the Phase III Randomized AMBER and EMERALD Trials. AIDS Res Hum Retroviruses. 2020 Jan;36(1):48-57. doi: 10.1089/AID.2019.0111. Epub 2019 Oct 21.

  PMID: 31516033 DERIVED

• Huhn GD, Eron JJ, Girard PM, Orkin C, Molina JM, DeJesus E, Petrovic R, Luo D, Van Landuyt E, Lathouwers E, Nettles RE, Brown K, Wong EY. Darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-experienced, virologically suppressed patients with HIV-1: subgroup analyses of the phase 3 EMERALD study. AIDS Res Ther. 2019 Aug 29;16(1):23. doi: 10.1186/s12981-019-0235-1.

  PMID: 31464642 DERIVED

• Orkin C, Molina JM, Negredo E, Arribas JR, Gathe J, Eron JJ, Van Landuyt E, Lathouwers E, Hufkens V, Petrovic R, Vanveggel S, Opsomer M; EMERALD study group. Efficacy and safety of switching from boosted protease inhibitors plus emtricitabine and tenofovir disoproxil fumarate regimens to single-tablet darunavir, cobicistat, emtricitabine, and tenofovir alafenamide at 48 weeks in adults with virologically suppressed HIV-1 (EMERALD): a phase 3, randomised, non-inferiority trial. Lancet HIV. 2018 Jan;5(1):e23-e34. doi: 10.1016/S2352-3018(17)30179-0. Epub 2017 Oct 6.

  PMID: 28993180 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Limitations and Caveats

The limitation of the study was the open-label design.

Results Point of Contact

• Title: Medical Officer
• Organization: Janssen Research & Development

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen R&D Ireland Clinical Trial

  Janssen R&D Ireland

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2014
• First Posted: October 21, 2014
• Study Start: March 1, 2015
• Primary Completion: February 1, 2017
• Study Completion: October 1, 2020
• Last Updated: December 9, 2021
• Results First Posted: November 9, 2018

Record last verified: 2021-11

Locations

CH (3); CA (4); GB (3); PR (1); FR (8); ES (9); US (38); PL (5); BE (5); SE (3)