Two Part Study to Evaluate Pharmacokinetics, Safety, and Antiviral Activity of Elvitegravir Administered With a PI/r Background Regimen for ARV Treatment-Experienced Pediatric Participants

NCT01923311 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: GS-US-183-01602013-001969-16
• Study Type: interventional
• Target: 31
• Locations: 6 countries
• Sites: 11

Brief Summary

The primary objectives of this study are to evaluate the safety, tolerability and steady-state PK and confirm the dose of EVG/r in HIV-1 infected, antiretroviral treatment-experienced children 4 weeks to \<18 years of age. The study consists of 2 parts: Part A and Part B. Part A will enroll participants with suppressed viremia (HIV-1 RNA \< 50 copies/mL) or failing a current antiretroviral (ARV) regimen (HIV-1 RNA \> 1,000 copies/mL only for participants in Cohort 2, Part A) to evaluate the steady state PK and confirm the dose of EVG. Part B will enroll participants who are failing a current ARV regimen (HIV-1 RNA \> 1,000 copies/mL) to evaluate the safety, tolerability, and antiviral activity of EVG. The study consists of 4 age cohorts with each cohort including 2 parts (Part A and Part B) with the exception of the adolescent age cohort (Cohort 1: 12 to \< 18 years old) containing Part B only.

Conditions

Acquired Immune Deficiency Syndrome (AIDS); HIV Infections

Keywords

Pediatrics; Adolescents; HIV; HIV-1; Treatment-experienced

Outcome Measures

Primary Outcomes (4)

• 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 and up to 12 hours postdose on Day 10

• Pharmacokinetic (PK) Parameter: Cmax of EVG at Day 10

  Cmax is defined as the maximum concentration of drug.

  Predose and up to 12 hours postdose on Day 10

• Percentage of Participants Experiencing Treatment-emergent Adverse Events

  Baseline up to the last dose date plus 30 days (maximum exposure: 173.6 weeks for participants age 6 to < 18 Years Screening HIV-1 RNA > 1000 copies/mL and 2.0 weeks for participants age 6 to < 12 Years Screening HIV-1 RNA < 50 copies/mL)

• Percentage of Participants Experiencing Laboratory Abnormalities

  Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each subject. The criteria used to grade laboratory results were as follows: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), and Grade 4 (life-threatening).

  Baseline up to the last dose date plus 30 days (maximum exposure: 173.6 weeks for participants age 6 to < 18 Years Screening HIV-1 RNA > 1000 copies/mL and 2.0 weeks for participants age 6 to < 12 Years Screening HIV-1 RNA < 50 copies/mL)

Secondary Outcomes (18)

• Pharmacokinetic (PK) Parameter: Ctau of EVG

  Predose and up to 12 hours postdose on Day 10

• Pharmacokinetic (PK) Parameter: CL/F of EVG

  Predose and up to 12 hours postdose on Day 10

• Pharmacokinetic (PK) Parameter: Vz/F of EVG

  Predose and up to 12 hours postdose on Day 10

• Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the FDA Snapshot Algorithm

  Week 24

• Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the FDA Snapshot Algorithm

  Week 48

Study Arms (4)

Cohort 1 (12 to < 18 years of age)

EXPERIMENTAL

Part A: No participants will be enrolled in Part A, as PK data is currently available for this age group. Part B: Participants will receive EVG plus a background regimen that includes a PI/r for up to 48 weeks. After Week 48, participants will be given the option to continue EVG therapy until the participant turns 18 and EVG is available for use in adults in the country in which the participant is enrolled, or the age appropriate EVG formulation becomes available for use in the country in which the participant is enrolled, or Gilead Sciences elects to terminate development of EVG in the applicable country.

Drug: EVG; Drug: Background regimen

Cohort 2 (6 to < 12 years of age)

EXPERIMENTAL

Part A: Participants with HIV-1 RNA \< 50 copies/mL will receive EVG plus a background regimen that includes a PI/r for 10 days. Participants with HIV-1 RNA \> 1,000 copies/mL will receive EVG along with a newly constructed background regimen that includes a Pl/r for 48 weeks. Participants with HIV-1 RNA \> 1,000 copies/mL can continue after Week 48. Part B: Following confirmation of exposure to EVG and based on safety and PK data assessed in Part A, participants will receive EVG plus a background regimen that includes a PI/r for up to 48 weeks. Participants who complete the 48-week follow-up in both Part A and Part B will be given the option to continue EVG therapy until the participant turns 18 and EVG is available for use in adults in the country in which the participant is enrolled, or the age appropriate EVG formulation becomes available for use in the country in which the participant is enrolled, or Gilead Sciences elects to terminate development of EVG in the applicable country.

Drug: EVG; Drug: Background regimen

Cohort 3 (2 to < 6 years of age)

EXPERIMENTAL

Part A: Participants with HIV-1 RNA \< 50 copies/mL will receive EVG plus a background regimen that includes a PI/r for 10 days. Part B: Following confirmation of exposure to EVG and based on safety and PK data assessed in Part A, participants will receive EVG plus a background regimen that includes a PI/r for up to 48 weeks. After Week 48, participants will be given the option to continue EVG therapy until the participant turns 18 and EVG is available for use in adults in the country in which the participant is enrolled, or the age appropriate EVG formulation becomes available for use in the country in which the participant is enrolled, or Gilead Sciences elects to terminate development of EVG in the applicable country.

Drug: EVG; Drug: Background regimen

Cohort 4 (4 weeks to < 2 years of age)

EXPERIMENTAL

Part A: Participants with HIV-1 RNA \< 50 copies/mL will receive EVG plus a background regimen that includes a PI/r for 10 days. Part B: Following confirmation of exposure to EVG and based on safety and PK data assessed in Part A, participants will receive EVG plus a background regimen that includes a PI/r for up to 48 weeks. After Week 48, participants will be given the option to continue EVG therapy until the participant turns 18 and EVG is available for use in adults in the country in which the participant is enrolled, or the age appropriate EVG formulation becomes available for use in the country in which the participant is enrolled, or Gilead Sciences elects to terminate development of EVG in the applicable country.

Drug: EVG; Drug: Background regimen

Interventions

EVG DRUG

Tablet (s) or tablet (s) for oral suspension (if unable to swallow) will be administered orally once daily

Also known as: Vitekta®

Cohort 1 (12 to < 18 years of age); Cohort 2 (6 to < 12 years of age); Cohort 3 (2 to < 6 years of age); Cohort 4 (4 weeks to < 2 years of age)

Background regimen DRUG

Background regimen may consist of the following ritonavir (RTV)-boosted PIs (PI/r): lopinavir/r (Kaletra), atazanavir/r, darunavir/r, tipranavir/r, or fosamprenavir/r. For participants \< 2 months old, only lopinavir/r is allowed. Use of additional antiretrovirals in background therapy may be allowed.

Cohort 1 (12 to < 18 years of age); Cohort 2 (6 to < 12 years of age); Cohort 3 (2 to < 6 years of age); Cohort 4 (4 weeks to < 2 years of age)

Eligibility Criteria

• Age: 4 Weeks - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• HIV-1 infected male and female individuals 4 weeks (gestational age of at least 44 weeks) to less than 18 years of age at Baseline.
• Individuals are able to provide written assent if they have the ability to read and write.
• Parent or legal guardian able to provide written informed consent prior to any screening evaluations and willing to comply with study requirements.
• Body weight at screening greater than 5kg, 10.6kg, or 15kg dependent upon age cohort
• Adequate renal function
• Adequate hematologic function
• Hepatic transaminases (AST and ALT) less than or equal to 5 x upper limit of normal (ULN)
• Total bilirubin less than or equal to 1.5 mg/dL, or normal direct bilirubin
• Negative serum pregnancy test
• Individuals with evidence of suppressed viremia
• Individuals failing a current antiretroviral regimen at study entry
• Male and female individuals of childbearing potential must agree to utilize highly effective contraception methods while on study treatment or agree to abstain from heterosexual intercourse of reproductive potential throughout the study period and for 30 days following the last dose of study drug
• Must be willing and able to comply with all study requirements.

You may not qualify if:

• Individuals with CD4+ cell counts at Screening of less than 50, 75, or 200 cells/mm3 dependent on age cohort
• An AIDS defining condition with onset within 30 days prior to screening
• Life expectancy of less than 1 year
• For Individuals with HIV-1 RNA greater than 1,000 copies/mL at screening, prior treatment of any duration with an integrase strand transfer inhibitor.
• An ongoing serious infection requiring systemic antibiotic therapy at the time of screening.
• Evidence of active pulmonary or extra-pulmonary tuberculosis disease
• Anticipated requirement for rifamycin treatment while participating in the study.
• Have any serious or active medical or psychiatric illness which, in the opinion of the Investigator, would interfere with Individual's treatment, assessment, or compliance with the protocol.
• Individuals experiencing decompensated cirrhosis
• A history of or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma.
• Pregnant or lactating females.
• Current alcohol or substance abuse judged by the Investigator to potentially interfere with individual's compliance.
• Have history of significant drug sensitivity or drug allergy.
• Known hypersensitivity to the study drug, the metabolites, or formulation excipients.
• Have previously participated in an investigational trial involving administration of any investigational agent within 30 days prior to the study dosing.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (11)

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Universita degli Studi di Pavia - Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

Location

Be Part Yoluntu Centre

Cape Town, 7646, South Africa

Location

Rahima Moosa Mother and Child Hopsital

Johannesburg, 2112, South Africa

Location

Hospital Universitario De Getafe

Getafe, Madrid, 28095, Spain

Location

Hospital 12 de Octubre

Madrid, 28041, Spain

Location

Thai Red Cross AIDS Research Centre (HIV-NAT)

Bangkok, 10330, Thailand

Location

Siriraj Hospital

Bangkok, 10700, Thailand

Location

Joint Clinical Research Centre

Kampala, Uganda

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; HIV Infections

Interventions

elvitegravir

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

Results Point of Contact

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

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2013
• First Posted: August 15, 2013
• Study Start: August 26, 2013
• Primary Completion: November 3, 2017
• Study Completion: November 3, 2017
• Last Updated: August 9, 2018
• Results First Posted: July 11, 2018

Record last verified: 2018-07

Locations

UG (1); TH (2); ES (2); ZA (2); US (3); IT (1)