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

NCT ID: NCT01721109

Last Updated: 2018-08-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-06
• Study Completion Date: 2018-01-29

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.

Conditions

Acquired Immunodeficiency Syndrome; HIV Infections

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

EVG/COBI/FTC/TDF

Intervention Type: DRUG

150/150/200/300 mg STR administered orally once daily with food

Interventions

EVG/COBI/FTC/TDF

150/150/200/300 mg STR administered orally once daily with food

Intervention Type: DRUG

Other Intervention Names

Stribild®

Eligibility Criteria

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

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

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

East Bay AIDS Center Medical Group

Oakland, California, United States

University of South Florida - Department of Pediatrics

Tampa, Florida, United States

University of Chicago

Chicago, Illinois, United States

New York University School of Medicine

New York, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, United States

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Rahima Moosa Mother and Child Hospital (Wits)

Johannesburg, Gauteng, South Africa

Dr Latiff Private Practice

Durban, KwaZulu-Natal, South Africa

Desmond Tutu HIV Research Centre

Cape Town, , South Africa

Mpati Medical Center

Dundee, , South Africa

Clinical HIV Research Unit

Johannesburg, , South Africa

Perinatal HIV Research Unit

Soweto, , South Africa

University of Stellenbosch

Stellenbosch, , South Africa

The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)

Bangkok, , Thailand

Siriraj Hospital, Mahidol University

Bangkok, , Thailand

Queen Savang Vadhana Memorial Hospital

Chon Buri, , Thailand

Srinakarind Hospital

Khon Kaen, , Thailand

Countries

United States; South Africa; Thailand

References

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

Reference Type: RESULT

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

Reference Type: RESULT

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

Reference Type: RESULT

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

Reference Type: RESULT

Other Identifiers

2015-000313-40

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-236-0112

Identifier Type: -

Identifier Source: org_study_id