Pharmacokinetics, Safety, and Efficacy of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate Single Tablet Regimen (STR) in Adolescents

July 20, 2018 updated by: Gilead Sciences

A Phase 2/3, Open-Label Study of the Pharmacokinetics, Safety, and Antiviral Activity of the Elvitegravir/ Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate Single Tablet Regimen (STR) in HIV-1 Infected Antiretroviral Treatment-Naive Adolescents

The primary objectives of this study are to evaluate the steady-state pharmacokinetics (PK) and confirm the dose of the elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) single-tablet regimen (STR) (Part A) and to evaluate the safety and tolerability of EVG/COBI/FTC/TDF STR through Week 48 (Part B) in HIV-1 infected, antiretroviral (ARV) treatment-naive adolescents.

A total of 50 adolescent participants (12 to < 18 years of age) will be enrolled to receive EVG/COBI/FTC/TDF as follows:

  • Part A: Twelve to 16 eligible participants will be enrolled to evaluate steady-state PK, and confirm the dose, with the intent to enroll at least 4 participants 12 to < 15 and at least 4 participants 15 to < 18 years of age.
  • Part B: Following confirmation of EVG exposure in at least 12 participants from Part A, 34 to 38 participants in addition to those enrolled in Part A will be enrolled to evaluate the safety, tolerability, and antiviral activity of EVG/COBI/FTC/TDF STR.

Study Overview

Status

Completed

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Cape Town, South Africa, 7925
        • Desmond Tutu HIV Research Centre
      • Dundee, South Africa, 3000
        • Mpati Medical Center
      • Johannesburg, South Africa, 2092
        • Clinical HIV Research Unit
      • Soweto, South Africa, 2013
        • Perinatal HIV Research Unit
      • Stellenbosch, South Africa, 7602
        • University of Stellenbosch
    • Gauteng
      • Johannesburg, Gauteng, South Africa, 2112
        • Rahima Moosa Mother and Child Hospital (Wits)
    • Kwazulu-Natal
      • Durban, Kwazulu-Natal, South Africa, 4001
        • Dr Latiff Private Practice
      • Bangkok, Thailand, 10330
        • The HIV Netherlands Australia Thailand Research collaboration (HIV-NAT)
      • Bangkok, Thailand, 10700
        • Siriraj Hospital, Mahidol University
      • Chon Buri, Thailand, 20110
        • Queen Savang Vadhana Memorial Hospital
      • Khon Kaen, Thailand, 40002
        • Srinakarind Hospital
    • California
      • Oakland, California, United States, 94609
        • East Bay AIDS Center Medical Group
    • Florida
      • Tampa, Florida, United States, 33606
        • University of South Florida - Department of Pediatrics
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago
    • New York
      • Bronx, New York, United States, 10467
        • Montefiore Medical Center
      • New York, New York, United States, 10016
        • New York University School of Medicine
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19134
        • St. Christopher's Hospital for Children
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • St. Jude Children's Research Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years to 17 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Key Inclusion Criteria:

  • 12 years to < 18 years of age at baseline
  • Able to give written assent prior to any screening evaluations
  • Parent or guardian able to give written informed consent prior to any screening evaluations and willing to comply with study requirements
  • Plasma HIV-1 RNA levels of ≥ 1,000 copies/mL
  • CD4+ cell count > 100 cells/µL
  • Weight ≥ 35 kg (77 lbs)
  • Screening genotype report must show sensitivity to FTC and TDF
  • Able to swallow oral tablets
  • Adequate renal function
  • Clinically normal ECG
  • Documented screening for active pulmonary tuberculosis per local standard of care within 6 months of a screening visit
  • Hepatic transaminases ≤ 5 x upper limit of normal
  • Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
  • Individuals with a positive Hepatitis B surface antigen screening test can participate in the study, providing that alternate therapy (other than TDF) for chronic Hepatitis B infection is available as a part of local standard of care
  • Adequate hematologic function
  • Negative serum pregnancy test for all females
  • Males and females of childbearing potential must agree to utilize highly effective contraception methods while on study treatment or agree to abstain from heterosexual intercourse throughout the study period and for 30 days following the last dose of study drug
  • Males must agree to utilize a highly effective method of contraception during heterosexual intercourse throughout the study period and for 30 days following discontinuation of investigational medicinal product
  • Must be willing and able to comply with all study requirements
  • Life expectancy ≥ 1 year

Key Exclusion Criteria:

  • A new AIDS-defining condition diagnosed within the 30 days prior to screening
  • Prior treatment with any approved or investigational or experimental anti HIV-1 drug for any length of time (other than that given for prevention of mother-to-child transmission)
  • Evidence of active pulmonary or extra-pulmonary tuberculosis disease within 3 months of the screening visit
  • Anticipated to require rifamycin treatment for mycobacterial infection while participating in the study. Note: prophylactic Isoniazid (INH) therapy for latent tuberculosis (TB) treatment is allowed.
  • Individuals experiencing decompensated cirrhosis
  • Pregnant or lactating females
  • Have any serious or active medical or psychiatric illness which would interfere with treatment, assessment, or compliance with the protocol. This would include uncontrolled renal, cardiac, hematological, hepatic, pulmonary, endocrine, central nervous, gastrointestinal, vascular, metabolic, immunodeficiency disorders, active infection, or malignancy that are clinically significant or requiring treatment within 30 days prior to the study dosing.
  • Current alcohol or substance abuse that will potentially interfere with compliance
  • Have history of significant drug sensitivity or drug allergy
  • Known hypersensitivity to the study drugs, the metabolites or formulation excipients
  • Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening or expected to receive these agents during the study
  • A history of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma
  • Have previously participated in an investigational trial involving administration of any investigational agent within 30 days prior to the study dosing
  • Participation in any other clinical trial without prior approval from sponsor is prohibited while participating in this trial
  • Receiving ongoing therapy with any disallowed medications, including drugs not to be used with EVG, COBI, FTC, TDF or individuals with any known allergies to the excipients of EVG/COBI/FTC/TDF STR tablets

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: EVG/COBI/FTC/TDF
Participants will receive treatment for 48 weeks and then had the option to enter an Extension Phase to receive EVG/COBI/FTC/TDF until 1) the age of 18, 2) EVG/COBI/FTC/TDF becomes commercially available in the country the participant is enrolled, or 3) Gilead elects to terminate the development of EVG/COBI/FTC/TDF in that country.
150/150/200/300 mg STR administered orally once daily with food
Other Names:
  • Stribild®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
For Part A, Pharmacokinetic (PK) Parameter: AUCtau of EVG
Time Frame: Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
Incidence of Treatment-Emergent Serious Adverse Events (SAEs) and All Treatment-Emergent Adverse Events (AEs)
Time Frame: Up to Week 48 plus 30 days
Up to Week 48 plus 30 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
For Part A, PK Parameter: Ctau of EVG, FTC, Tenofovir (TFV), and COBI
Time Frame: Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
Ctau is defined as the observed drug concentration at the end of the dosing interval.
Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
For Part A, PK Parameter: Cmax of EVG, FTC, TFV, and COBI
Time Frame: Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
Cmax is defined as the maximum concentration of drug.
Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
For Part A, PK Parameter: AUCtau of FTC, TFV, and COBI
Time Frame: Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 24 and 48 as Defined by the FDA Snapshot Analysis
Time Frame: Weeks 24 and 48
Weeks 24 and 48
Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Weeks 24 and 48 as Defined by the FDA Snapshot Analysis
Time Frame: Weeks 24 and 48
Weeks 24 and 48
Change From Baseline in Plasma log10 HIV-1 RNA at Weeks 24 and 48
Time Frame: Baseline; Weeks 24 and 48
Baseline; Weeks 24 and 48
Change From Baseline in CD4+ Cell Count at Weeks 24 and 48
Time Frame: Baseline; Weeks 24 and 48
Baseline; Weeks 24 and 48
Change From Baseline in CD4 Percentage at Weeks 24 and 48
Time Frame: Baseline; Weeks 24 and 48
Baseline; Weeks 24 and 48

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

  • Gaur A, Fourie J, Chokephaibulkit K, Bekker L-G, Yin X, Custodio J, Bennett S, Cheng A, Quirk E. Pharmacokinetics, Efficacy and Safety of an Integrase Inhibitor-Based Single-Tablet Regimen in HIV-Infected Treatment-Naïve Adolescents. 21st Conference on Retroviruses and Opportunistic Infections (CROI). March 2014. Boston, MA, USA
  • Chokephaibulkit K, Gaur A, Fourie J, Bekker L-G, Shao Y, Custodio J, Bennett S, Cheng A, Quirk E. Safety and Efficacy of the Integrase Inhibitor-Based Stribild Single-Tablet Regimen in HIV-Infected Adolescents Through 24 Weeks of Treatment. 20th International AIDS Conference. July 2014. Melbourne, Australia
  • Porter DP, Bennett S, Quirk E, Miller MD, White KL. Lack of Emergent Resistance in HIV-1-Infected Adolescents on Elvitegravir-Based STRs. 22nd Conference on Retroviruses and Opportunistic Infections (CROI). February 2015. Seattle, WA, USA
  • Kizito H, Gaur A, Prasitsuebsai W, Rakhmanina N, Chokephaibulkit K, Fourie J, Bekker LG, Shao Y, Bennett S, Quirk E. Changes in renal laboratory markers and bone mineral density in treatment-naïve HIV-1-infected adolescents initiating INSTI-based single-tablet regimens containing tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF). 8th IAS Conference on HIV Pathogenesis, Treatment & Prevention. July 2015. Vancouver, Canada

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 6, 2012

Primary Completion (Actual)

October 22, 2015

Study Completion (Actual)

January 29, 2018

Study Registration Dates

First Submitted

November 1, 2012

First Submitted That Met QC Criteria

November 1, 2012

First Posted (Estimate)

November 4, 2012

Study Record Updates

Last Update Posted (Actual)

August 17, 2018

Last Update Submitted That Met QC Criteria

July 20, 2018

Last Verified

July 1, 2018

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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