Clinical trial NCT01721109: 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
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Acquired Immunodeficiency Syndrome
HIV Infections
Keywords: Adolescents
HIV-1
HIV
Treatment Naive
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2012-11-04
Enrollment: 50
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: For Part A, Pharmacokinetic (PK) Parameter: AUCtau of EVG
timeFrame: Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
measure: Incidence of Treatment-Emergent Serious Adverse Events (SAEs) and All Treatment-Emergent Adverse Events (AEs)
timeFrame: Up to Week 48 plus 30 days
Secondary outcomes:
measure: For Part A, PK Parameter: Ctau of EVG, FTC, Tenofovir (TFV), and COBI
timeFrame: Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
measure: For Part A, PK Parameter: Cmax of EVG, FTC, TFV, and COBI
timeFrame: Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
measure: For Part A, PK Parameter: AUCtau of FTC, TFV, and COBI
timeFrame: Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 24 and 48 as Defined by the FDA Snapshot Analysis
timeFrame: Weeks 24 and 48
measure: Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Weeks 24 and 48 as Defined by the FDA Snapshot Analysis
timeFrame: Weeks 24 and 48
measure: Change From Baseline in Plasma log10 HIV-1 RNA at Weeks 24 and 48
timeFrame: Baseline; Weeks 24 and 48
measure: Change From Baseline in CD4+ Cell Count at Weeks 24 and 48
timeFrame: Baseline; Weeks 24 and 48
measure: Change From Baseline in CD4 Percentage at Weeks 24 and 48
timeFrame: Baseline; Weeks 24 and 48
Other outcomes:
Locations:
city: Oakland
country: United States
facility: East Bay AIDS Center Medical Group
state: California
city: Tampa
country: United States
facility: University of South Florida - Department of Pediatrics
state: Florida
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: New York University School of Medicine
state: New York
city: Philadelphia
country: United States
facility: St. Christopher's Hospital for Children
state: Pennsylvania
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Johannesburg
country: South Africa
facility: Rahima Moosa Mother and Child Hospital (Wits)
state: Gauteng
city: Durban
country: South Africa
facility: Dr Latiff Private Practice
state: Kwazulu-Natal
city: Cape Town
country: South Africa
facility: Desmond Tutu HIV Research Centre
city: Dundee
country: South Africa
facility: Mpati Medical Center
city: Johannesburg
country: South Africa
facility: Clinical HIV Research Unit
city: Soweto
country: South Africa
facility: Perinatal HIV Research Unit
city: Stellenbosch
country: South Africa
facility: University of Stellenbosch
city: Bangkok
country: Thailand
facility: The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)
city: Bangkok
country: Thailand
facility: Siriraj Hospital, Mahidol University
city: Chon Buri
country: Thailand
facility: Queen Savang Vadhana Memorial Hospital
city: Khon Kaen
country: Thailand
facility: Srinakarind Hospital
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
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
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
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
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