A Study to Evaluate Efficacy and Safety of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) Fixed Dose Combination (FDC) Versus a Regimen Consisting of Darunavir/Cobicistat FDC With Emtricitabine/Tenofovir Disoproxil Fumarate FDC in Treatment-naive HIV Type 1 Infected Subjects

NCT ID: NCT02431247

Last Updated: 2022-09-28

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

725 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-07-06

Study Completion Date

2020-09-30

Brief Summary

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The purpose of this study is to demonstrate non-inferiority in efficacy of a darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) fixed dose combination (FDC) tablet versus Darunavir/Cobicistat (DRV/COBI) FDC coadministered with Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) FDC in human immunodeficiency virus-1 (HIV-1) infected, antiretroviral (ARV) treatment naive adult participants.

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Detailed Description

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This is a Phase 3, multicenter (when more than one hospital or medical school team work on a medical research study), randomized (study drug assigned by chance), double-blind (a medical research study in which neither the researchers nor the participant know what treatment the participant is receiving), active-controlled (study in which the experimental treatment or procedure is compared to a standard \[control\] treatment or procedure) study. The study consists of 5 periods: a Screening period, Double-blind treatment period, Single-arm treatment period, Extension period and a Follow-up period. Participants will receive either darunavir (DRV)/ cobicistat (COBI)/emtricitabine (FTC) /tenofovir alafenamide (TAF) fixed dose combination (D/C/F/TAF FDC) or DRV/COBI FDC along with FTC/TDF FDC. Primarily percentage of participants with human immunodeficiency virus (HIV) -1 Ribonucleic acid (RNA) less than (\<) 50 copies per milliliter (copies/ml) defined by snapshot analysis will be evaluated. Participants' safety will be monitored throughout the study.

Conditions

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Immunodeficiency Virus Type 1, Human

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide

Subject will receive a single oral tablet containing darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination \[FDC\]) once daily along with DRV/COBI FDC-matching and FTC/TDF FDC-matching placebo tablets once daily up to Week 48 analysis unblinding visit (i.e. after last subject has reached Week 48). After Week 48 analysis unblinding visit, subjects will receive a single tablet containing D/C/F/TAF FDC once daily up to Week 96.

Group Type EXPERIMENTAL

Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide FDC

Intervention Type DRUG

A tablet containing DRV 800 mg, COBI 150 mg, FTC 200 mg and TAF) 10 mg will be administered once daily.

FTC/TDF FDC Matching Placebo

Intervention Type DRUG

Matching placebo of FTC/TDF FDC will be administered once daily.

DRV/COBI FDC Matching Placebo

Intervention Type DRUG

Matching placebo of DRV/COBI FDC will be administered once daily.

DRV/COBI fixed dose combination (FDC) and FTC/TDF FDC

Subject will receive DRV 800 mg/COBI 150 mg FDC and FTC 200 mg/TDF 300 mg FDC along with D/C/F/TAF FDC-matching placebo tablet once daily up to Week 48 analysis unblinding (i.e. after last subject has reached Week 48). After Week 48 analysis unblinding, subjects will receive a single tablet containing D/C/F/TAF FDC once daily up to Week 96.

Group Type ACTIVE_COMPARATOR

DRV/COBI FDC

Intervention Type DRUG

A tablet containing DRV 800 mg and COBI 150 mg will be administered once daily.

FTC/TDF FDC

Intervention Type DRUG

A tablet containing FTC 200 mg and TDF 300 mg will be administered once daily.

D/C/F/TAF FDC - Matching Placebo

Intervention Type DRUG

Matching placebo of D/C/F/TAF FDC will be administered once daily.

Interventions

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Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide FDC

A tablet containing DRV 800 mg, COBI 150 mg, FTC 200 mg and TAF) 10 mg will be administered once daily.

Intervention Type DRUG

DRV/COBI FDC

A tablet containing DRV 800 mg and COBI 150 mg will be administered once daily.

Intervention Type DRUG

FTC/TDF FDC

A tablet containing FTC 200 mg and TDF 300 mg will be administered once daily.

Intervention Type DRUG

D/C/F/TAF FDC - Matching Placebo

Matching placebo of D/C/F/TAF FDC will be administered once daily.

Intervention Type DRUG

FTC/TDF FDC Matching Placebo

Matching placebo of FTC/TDF FDC will be administered once daily.

Intervention Type DRUG

DRV/COBI FDC Matching Placebo

Matching placebo of DRV/COBI FDC will be administered once daily.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Subject must be antiretroviral (ARV) treatment-naive (never treated with an ARV including post-exposure prophylaxis and pre-exposure prophylaxis); no prior use of any approved or experimental anti- human immunodeficiency virus (anti-HIV) drug for any length of time
* Screening plasma HIV-1 ribonucleic acid (RNA) level greater than or equal to \>=1,000 copies per milliliter (copies/mL)
* Cluster of Differentiation 4+ (CD4+) cell count \>50 cells/microliter (cells/mcL)
* Screening HIV-1 genotype report must show full sensitivity to DRV, TDF and FTC
* Screening eGFRcreatinine \>=70 mL/min according to the Cockcroft-Gault formula for creatinine clearance

Exclusion Criteria

* Subject has been diagnosed with a new acquired immunodeficiency syndrome (AIDS)-defining condition within the 30 days prior to screening
* Subject has proven or suspected acute hepatitis within 30 days prior to screening
* Subject is hepatitis C or hepatitis B positive
* Subject has a history of cirrhosis
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Janssen Sciences Ireland UC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Janssen Sciences Ireland UC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Sciences Ireland UC

Locations

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Birmingham, Alabama, United States

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Phoenix, Arizona, United States

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Bakersfield, 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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North Hollywood, 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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Ft. Pierce, Florida, United States

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Miami, 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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Savannah, Georgia, 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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Minneapolis, Minnesota, 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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Manhasset, 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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Fort Worth, Texas, United States

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Houston, 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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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Clamart, , France

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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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Berlin, , Germany

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Bonn, , Germany

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Cologne, , Germany

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Essen, , Germany

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Frankfurt, , Germany

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Freiburg im Breisgau, , Germany

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Hamburg, , Germany

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Hanover, , Germany

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München, , Germany

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Bydgoszcz, , Poland

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Chorzów, , Poland

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Krakow, , Poland

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Lodz, , Poland

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Szczecin, , 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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Krasnodar, , Russia

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Oryol, , Russia

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Saint Petersburg, , Russia

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Saratov, , Russia

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Smolensk, , Russia

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Tolyatti, , Russia

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Voronezh, , Russia

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Yekaterinburg, , Russia

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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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Elche, , Spain

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Madrid, , Spain

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Santiago de Compostela, , Spain

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Seville, , Spain

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Valencia, , Spain

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Brighton, , United Kingdom

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Bristol, , United Kingdom

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London, , United Kingdom

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Countries

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United States Belgium Canada France Germany Poland Puerto Rico Russia Spain United Kingdom

References

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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.

Reference Type DERIVED
PMID: 34100149 (View on PubMed)

Orkin C, Eron JJ, Rockstroh J, Podzamczer D, Esser S, Vandekerckhove L, Van Landuyt E, Lathouwers E, Hufkens V, Jezorwski J, Opsomer M; AMBER study group. Week 96 results of a phase 3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients. AIDS. 2020 Apr 1;34(5):707-718. doi: 10.1097/QAD.0000000000002463.

Reference Type DERIVED
PMID: 31833849 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31516033 (View on PubMed)

Rashbaum B, Spinner CD, McDonald C, Mussini C, Jezorwski J, Luo D, Van Landuyt E, Brown K, Wong EY. Darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive patients with HIV-1: subgroup analyses of the phase 3 AMBER study. HIV Res Clin Pract. 2019 Feb;20(1):24-33. doi: 10.1080/15284336.2019.1608714. Epub 2019 May 29.

Reference Type DERIVED
PMID: 31303147 (View on PubMed)

Eron JJ, Orkin C, Gallant J, Molina JM, Negredo E, Antinori A, Mills A, Reynes J, Van Landuyt E, Lathouwers E, Hufkens V, Jezorwski J, Vanveggel S, Opsomer M; AMBER study group. A week-48 randomized phase-3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients. AIDS. 2018 Jul 17;32(11):1431-1442. doi: 10.1097/QAD.0000000000001817.

Reference Type DERIVED
PMID: 29683855 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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TMC114FD2HTX3001

Identifier Type: OTHER

Identifier Source: secondary_id

2015-000754-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR107277

Identifier Type: -

Identifier Source: org_study_id

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