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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01923311
• Other study ID #: GS-US-183-0160
• Secondary ID: 2013-001969-16
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: August 26, 2013
• Est. completion date: November 3, 2017

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 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 31
• Est. completion date: November 3, 2017
• Est. primary completion date: November 3, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acquired Immune Deficiency Syndrome (AIDS)
• Acquired Immunodeficiency Syndrome
• HIV Infections
• Immunologic Deficiency Syndromes

Intervention

Drug:
• EVG
Tablet (s) or tablet (s) for oral suspension (if unable to swallow) will be administered orally once daily
• Background regimen
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.

Locations

Country	Name	City	State
Italy	Universita degli Studi di Pavia - Fondazione IRCCS Policlinico San Matteo	Pavia
South Africa	Be Part Yoluntu Centre	Cape Town
South Africa	Rahima Moosa Mother and Child Hopsital	Johannesburg
Spain	Hospital Universitario De Getafe	Getafe	Madrid
Spain	Hospital 12 de Octubre	Madrid
Thailand	Siriraj Hospital	Bangkok
Thailand	Thai Red Cross AIDS Research Centre (HIV-NAT)	Bangkok
Uganda	Joint Clinical Research Centre	Kampala
United States	University of Colorado Denver	Aurora	Colorado
United States	Duke University Medical Center	Durham	North Carolina
United States	St. Jude Children's Research Hospital	Memphis	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Italy,  South Africa,  Spain,  Thailand,  Uganda, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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)
Primary	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	Pharmacokinetic (PK) Parameter: Ctau of EVG	Ctau is defined as the observed drug concentration at the end of the dosing interval.	Predose and up to 12 hours postdose on Day 10
Secondary	Pharmacokinetic (PK) Parameter: CL/F of EVG	CL/F is defined as the apparent oral clearance following administration of the drug.	Predose and up to 12 hours postdose on Day 10
Secondary	Pharmacokinetic (PK) Parameter: Vz/F of EVG	Vz/F is defined as the apparent volume of distribution of the drug.	Predose and up to 12 hours postdose on Day 10
Secondary	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the FDA Snapshot Algorithm	The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.	Week 24
Secondary	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the FDA Snapshot Algorithm	The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.	Week 48
Secondary	Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 24 as Defined by the FDA Snapshot Algorithm	The percentage of participants achieving HIV-1 RNA < 400 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.	Week 24
Secondary	Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 48 as Defined by the FDA Snapshot Algorithm	The percentage of participants achieving HIV-1 RNA < 400 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.	Week 48
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Week 24		Baseline to Week 24
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Week 48		Baseline to Week 48
Secondary	Change From Baseline in CD4 Cell Count at Week 24		Baseline to Week 24
Secondary	Change From Baseline in CD4 Cell Count at Week 48		Baseline to Week 48
Secondary	Change From Baseline in CD4 Percentage at Week 24		Baseline to Week 24
Secondary	Change From Baseline in CD4 Percentage at Week 48		Baseline to Week 48
Secondary	Tanner Stage Evaluation by Sex at Week 24	Tanner Stage (pubic hair and breasts for females; pubic hair and genitalia for males) at Week 24 visit was summarized using frequency count and percentage. Tanner Stages is a scale that defines physical measurements of development based on external primary and secondary sex characteristics. It was used in this study to assess pubertal development with values ranging from Stage 1 (pre-pubertal characteristics) to Stage 5 (adult or mature characteristics).	Week 24
Secondary	Tanner Stage Evaluation by Sex at Week 48	Tanner Stage (pubic hair and breasts for females; pubic hair and genitalia for males) at Week 48 visit was summarized using frequency count and percentage. Tanner Stages is a scale that defines physical measurements of development based on external primary and secondary sex characteristics. It was used in this study to assess pubertal development with values ranging from Stage 1 (pre-pubertal characteristics) to Stage 5 (adult or mature characteristics).	Week 48
Secondary	Age of First Menses	Age of first menses for female participants.	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)
Secondary	Palatability of Oral Suspension Formulation of EVG in Appropriate Age Group		Up to Week 48
Secondary	Adherence to EVG	Adherence was calculated as the number of pills taken divided by number of pills prescribed multiplied by 100.	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)