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

NCT01721109 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: GS-US-236-01122015-000313-40
• Study Type: interventional
• Target: 50
• Locations: 3 countries
• Sites: 18

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

Keywords

Adolescents; HIV-1; HIV; Treatment Naive

Outcome Measures

Primary Outcomes (2)

• 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

• Incidence of Treatment-Emergent Serious Adverse Events (SAEs) and All Treatment-Emergent Adverse Events (AEs)

  Up to Week 48 plus 30 days

Secondary Outcomes (8)

• For Part A, PK Parameter: Ctau of EVG, FTC, Tenofovir (TFV), and COBI

  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

  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

  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

  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

  Weeks 24 and 48

Study Arms (1)

EVG/COBI/FTC/TDF

EXPERIMENTAL

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.

Drug: EVG/COBI/FTC/TDF

Interventions

EVG/COBI/FTC/TDF DRUG

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

Also known as: Stribild®

EVG/COBI/FTC/TDF

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (18)

East Bay AIDS Center Medical Group

Oakland, California, 94609, United States

Location

University of South Florida - Department of Pediatrics

Tampa, Florida, 33606, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

New York University School of Medicine

New York, New York, 10016, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, 19134, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Rahima Moosa Mother and Child Hospital (Wits)

Johannesburg, Gauteng, 2112, South Africa

Location

Dr Latiff Private Practice

Durban, KwaZulu-Natal, 4001, South Africa

Location

Desmond Tutu HIV Research Centre

Cape Town, 7925, South Africa

Location

Mpati Medical Center

Dundee, 3000, South Africa

Location

Clinical HIV Research Unit

Johannesburg, 2092, South Africa

Location

Perinatal HIV Research Unit

Soweto, 2013, South Africa

Location

University of Stellenbosch

Stellenbosch, 7602, South Africa

Location

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

Bangkok, 10330, Thailand

Location

Siriraj Hospital, Mahidol University

Bangkok, 10700, Thailand

Location

Queen Savang Vadhana Memorial Hospital

Chon Buri, 20110, Thailand

Location

Srinakarind Hospital

Khon Kaen, 40002, Thailand

Location

Related Publications (4)

• 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

  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

  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

  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

  RESULT

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; HIV Infections

Interventions

Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cobicistat; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Tenofovir; Organophosphonates; Organophosphorus Compounds; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2012
• First Posted: November 5, 2012
• Study Start: December 6, 2012
• Primary Completion: October 22, 2015
• Study Completion: January 29, 2018
• Last Updated: August 17, 2018
• Results First Posted: April 10, 2017

Record last verified: 2018-07

Locations

ZA (7); US (7); TH (4)