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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01721109
• Other study ID #: GS-US-236-0112
• Secondary ID: 2015-000313-40
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: December 6, 2012
• Est. completion date: January 29, 2018

Study information

• Verified date: July 2018
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: January 29, 2018
• Est. primary completion date: October 22, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Immunologic Deficiency Syndromes

Intervention

Drug:
• EVG/COBI/FTC/TDF
150/150/200/300 mg STR administered orally once daily with food

Locations

Country	Name	City	State
South Africa	Desmond Tutu HIV Research Centre	Cape Town
South Africa	Mpati Medical Center	Dundee
South Africa	Dr Latiff Private Practice	Durban	Kwazulu-Natal
South Africa	Clinical HIV Research Unit	Johannesburg
South Africa	Rahima Moosa Mother and Child Hospital (Wits)	Johannesburg	Gauteng
South Africa	Perinatal HIV Research Unit	Soweto
South Africa	University of Stellenbosch	Stellenbosch
Thailand	Siriraj Hospital, Mahidol University	Bangkok
Thailand	The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)	Bangkok
Thailand	Queen Savang Vadhana Memorial Hospital	Chon Buri
Thailand	Srinakarind Hospital	Khon Kaen
United States	Montefiore Medical Center	Bronx	New York
United States	University of Chicago	Chicago	Illinois
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	New York University School of Medicine	New York	New York
United States	East Bay AIDS Center Medical Group	Oakland	California
United States	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania
United States	University of South Florida - Department of Pediatrics	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  South Africa,  Thailand, 

References & Publications (4)

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 Internati

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 Re

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-t

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
Primary	Incidence of Treatment-Emergent Serious Adverse Events (SAEs) and All Treatment-Emergent Adverse Events (AEs)		Up to Week 48 plus 30 days
Secondary	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.	Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
Secondary	For Part A, PK Parameter: Cmax of EVG, FTC, TFV, and COBI	Cmax is defined as the maximum concentration of drug.	Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
Secondary	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).	Predose, 2, 4, 4.5, 5, 8, and 12 hours postdose on Day 10
Secondary	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 24 and 48 as Defined by the FDA Snapshot Analysis		Weeks 24 and 48
Secondary	Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Weeks 24 and 48 as Defined by the FDA Snapshot Analysis		Weeks 24 and 48
Secondary	Change From Baseline in Plasma log10 HIV-1 RNA at Weeks 24 and 48		Baseline; Weeks 24 and 48
Secondary	Change From Baseline in CD4+ Cell Count at Weeks 24 and 48		Baseline; Weeks 24 and 48
Secondary	Change From Baseline in CD4 Percentage at Weeks 24 and 48		Baseline; Weeks 24 and 48