Clinical trial NCT01923311: 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
Official title: A Phase 2/3 Multicenter, Open-Label, Multicohort, Two-Part Study Evaluating the Pharmacokinetics (PK), Safety, and Antiviral Activity of Elvitegravir (EVG) Administered With a Background-Regimen (BR) Containing a Ritonavir-Boosted Protease Inhibitor (PI/r) in HIV-1 Infected, Antiretroviral Treatment-Experienced Pediatric Subjects
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Acquired Immune Deficiency Syndrome (AIDS)
HIV Infections
Keywords: Pediatrics
Adolescents
HIV
HIV-1
Treatment-experienced
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2013-08-15
Enrollment: 31
Sex: ALL
Minimum age (years): 4
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Key Inclusion Criteria:

Individuals must meet all of the following inclusion criteria to be eligible for participation in this study. Individuals with screening results that do not meet eligibility criteria will not be allowed to rescreen.

* 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.

Key Exclusion Criteria:

Participants who meet any of the following exclusion criteria are not to be enrolled in this study.

* 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.
* Participation in any other clinical trial without prior approval from sponsor is prohibited while participating in this trial.
* Individuals receiving ongoing therapy with any medication that is not to be taken with EVG or a component of the BR, including drugs not to be used with ritonavir

Note: Other protocol defined Inclusion/ Exclusion criteria may apply.

Primary outcomes:
measure: Pharmacokinetic (PK) Parameter: AUCtau of EVG
timeFrame: Predose and up to 12 hours postdose on Day 10
measure: Pharmacokinetic (PK) Parameter: Cmax of EVG at Day 10
timeFrame: Predose and up to 12 hours postdose on Day 10
measure: Percentage of Participants Experiencing Treatment-emergent Adverse Events
timeFrame: 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)
measure: Percentage of Participants Experiencing Laboratory Abnormalities
timeFrame: 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:
measure: Pharmacokinetic (PK) Parameter: Ctau of EVG
timeFrame: Predose and up to 12 hours postdose on Day 10
measure: Pharmacokinetic (PK) Parameter: CL/F of EVG
timeFrame: Predose and up to 12 hours postdose on Day 10
measure: Pharmacokinetic (PK) Parameter: Vz/F of EVG
timeFrame: Predose and up to 12 hours postdose on Day 10
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the FDA Snapshot Algorithm
timeFrame: Week 24
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the FDA Snapshot Algorithm
timeFrame: Week 48
measure: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 24 as Defined by the FDA Snapshot Algorithm
timeFrame: Week 24
measure: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 48 as Defined by the FDA Snapshot Algorithm
timeFrame: Week 48
measure: Change From Baseline in Plasma Log₁₀ HIV-1 RNA at Week 24
timeFrame: Baseline to Week 24
measure: Change From Baseline in Plasma Log₁₀ HIV-1 RNA at Week 48
timeFrame: Baseline to Week 48
measure: Change From Baseline in CD4 Cell Count at Week 24
timeFrame: Baseline to Week 24
measure: Change From Baseline in CD4 Cell Count at Week 48
timeFrame: Baseline to Week 48
measure: Change From Baseline in CD4 Percentage at Week 24
timeFrame: Baseline to Week 24
measure: Change From Baseline in CD4 Percentage at Week 48
timeFrame: Baseline to Week 48
measure: Tanner Stage Evaluation by Sex at Week 24
timeFrame: Week 24
measure: Tanner Stage Evaluation by Sex at Week 48
timeFrame: Week 48
measure: Age of First Menses
timeFrame: Baseline through end of study (maximum exposure: 173.6 weeks for participants age 6 to < 18 Years with Screening HIV-1 RNA > 1000 copies/mL and 2.0 weeks for participants age 6 to < 12 Years with Screening HIV-1 RNA < 50 copies/mL)
measure: Palatability of Oral Suspension Formulation of EVG in Appropriate Age Group
timeFrame: Up to Week 48
measure: Adherence to EVG
timeFrame: Baseline up to the last dose date (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)
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Pavia
country: Italy
facility: Universita degli Studi di Pavia - Fondazione IRCCS Policlinico San Matteo
city: Cape Town
country: South Africa
facility: Be Part Yoluntu Centre
city: Johannesburg
country: South Africa
facility: Rahima Moosa Mother and Child Hopsital
city: Getafe
country: Spain
facility: Hospital Universitario De Getafe
state: Madrid
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Bangkok
country: Thailand
facility: Thai Red Cross AIDS Research Centre (HIV-NAT)
city: Bangkok
country: Thailand
facility: Siriraj Hospital
city: Kampala
country: Uganda
facility: Joint Clinical Research Centre
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: