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

Primary Purpose

Acquired Immunodeficiency Syndrome, HIV Infections

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
EVG/COBI/FTC/TDF
Sponsored by
Gilead Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acquired Immunodeficiency Syndrome focused on measuring Adolescents, HIV-1, HIV, Treatment Naive

Eligibility Criteria

12 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • East Bay AIDS Center Medical Group
  • University of South Florida - Department of Pediatrics
  • University of Chicago
  • Montefiore Medical Center
  • New York University School of Medicine
  • St. Christopher's Hospital for Children
  • St. Jude Children's Research Hospital
  • Rahima Moosa Mother and Child Hospital (Wits)
  • Dr Latiff Private Practice
  • Desmond Tutu HIV Research Centre
  • Mpati Medical Center
  • Clinical HIV Research Unit
  • Perinatal HIV Research Unit
  • University of Stellenbosch
  • The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)
  • Siriraj Hospital, Mahidol University
  • Queen Savang Vadhana Memorial Hospital
  • Srinakarind Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

EVG/COBI/FTC/TDF

Arm Description

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.

Outcomes

Primary Outcome Measures

For Part A, Pharmacokinetic (PK) Parameter: AUCtau of EVG
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Incidence of Treatment-Emergent Serious Adverse Events (SAEs) and All Treatment-Emergent Adverse Events (AEs)

Secondary Outcome Measures

For Part A, PK Parameter: Ctau of EVG, FTC, Tenofovir (TFV), and COBI
Ctau is defined as the observed drug concentration at the end of the dosing interval.
For Part A, PK Parameter: Cmax of EVG, FTC, TFV, and COBI
Cmax is defined as the maximum concentration of drug.
For Part A, PK Parameter: AUCtau of FTC, TFV, and COBI
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 24 and 48 as Defined by the FDA Snapshot Analysis
Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Weeks 24 and 48 as Defined by the FDA Snapshot Analysis
Change From Baseline in Plasma log10 HIV-1 RNA at Weeks 24 and 48
Change From Baseline in CD4+ Cell Count at Weeks 24 and 48
Change From Baseline in CD4 Percentage at Weeks 24 and 48

Full Information

First Posted
November 1, 2012
Last Updated
July 20, 2018
Sponsor
Gilead Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT01721109
Brief Title
Pharmacokinetics, Safety, and Efficacy of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate Single Tablet Regimen (STR) in Adolescents
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
December 6, 2012 (Actual)
Primary Completion Date
October 22, 2015 (Actual)
Study Completion Date
January 29, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acquired Immunodeficiency Syndrome, HIV Infections
Keywords
Adolescents, HIV-1, HIV, Treatment Naive

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
EVG/COBI/FTC/TDF
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
EVG/COBI/FTC/TDF
Other Intervention Name(s)
Stribild®
Intervention Description
150/150/200/300 mg STR administered orally once daily with food
Primary Outcome Measure Information:
Title
For Part A, Pharmacokinetic (PK) Parameter: AUCtau of EVG
Description
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Time Frame
Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
Title
Incidence of Treatment-Emergent Serious Adverse Events (SAEs) and All Treatment-Emergent Adverse Events (AEs)
Time Frame
Up to Week 48 plus 30 days
Secondary Outcome Measure Information:
Title
For Part A, PK Parameter: Ctau of EVG, FTC, Tenofovir (TFV), and COBI
Description
Ctau is defined as the observed drug concentration at the end of the dosing interval.
Time Frame
Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
Title
For Part A, PK Parameter: Cmax of EVG, FTC, TFV, and COBI
Description
Cmax is defined as the maximum concentration of drug.
Time Frame
Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
Title
For Part A, PK Parameter: AUCtau of FTC, TFV, and COBI
Description
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Time Frame
Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
Title
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
Title
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
Title
Change From Baseline in Plasma log10 HIV-1 RNA at Weeks 24 and 48
Time Frame
Baseline; Weeks 24 and 48
Title
Change From Baseline in CD4+ Cell Count at Weeks 24 and 48
Time Frame
Baseline; Weeks 24 and 48
Title
Change From Baseline in CD4 Percentage at Weeks 24 and 48
Time Frame
Baseline; Weeks 24 and 48

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
East Bay AIDS Center Medical Group
City
Oakland
State/Province
California
ZIP/Postal Code
94609
Country
United States
Facility Name
University of South Florida - Department of Pediatrics
City
Tampa
State/Province
Florida
ZIP/Postal Code
33606
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
New York University School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
St. Christopher's Hospital for Children
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19134
Country
United States
Facility Name
St. Jude Children's Research Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States
Facility Name
Rahima Moosa Mother and Child Hospital (Wits)
City
Johannesburg
State/Province
Gauteng
ZIP/Postal Code
2112
Country
South Africa
Facility Name
Dr Latiff Private Practice
City
Durban
State/Province
Kwazulu-Natal
ZIP/Postal Code
4001
Country
South Africa
Facility Name
Desmond Tutu HIV Research Centre
City
Cape Town
ZIP/Postal Code
7925
Country
South Africa
Facility Name
Mpati Medical Center
City
Dundee
ZIP/Postal Code
3000
Country
South Africa
Facility Name
Clinical HIV Research Unit
City
Johannesburg
ZIP/Postal Code
2092
Country
South Africa
Facility Name
Perinatal HIV Research Unit
City
Soweto
ZIP/Postal Code
2013
Country
South Africa
Facility Name
University of Stellenbosch
City
Stellenbosch
ZIP/Postal Code
7602
Country
South Africa
Facility Name
The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)
City
Bangkok
ZIP/Postal Code
10330
Country
Thailand
Facility Name
Siriraj Hospital, Mahidol University
City
Bangkok
ZIP/Postal Code
10700
Country
Thailand
Facility Name
Queen Savang Vadhana Memorial Hospital
City
Chon Buri
ZIP/Postal Code
20110
Country
Thailand
Facility Name
Srinakarind Hospital
City
Khon Kaen
ZIP/Postal Code
40002
Country
Thailand

12. IPD Sharing Statement

Citations:
Citation
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
Results Reference
result
Citation
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
Results Reference
result
Citation
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
Results Reference
result
Citation
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
Results Reference
result

Learn more about this trial

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

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