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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

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ClinicalTrials.gov Identifier: NCT01923311
Recruitment Status : Terminated
First Posted : August 15, 2013
Results First Posted : July 11, 2018
Last Update Posted : August 9, 2018
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Description
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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.


Condition or disease Intervention/treatment Phase
Acquired Immune Deficiency Syndrome (AIDS) HIV Infections Drug: EVG Drug: Background regimen Phase 2 Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 31 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : August 26, 2013
Actual Primary Completion Date : November 3, 2017
Actual Study Completion Date : November 3, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arms and Interventions
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Arm Intervention/treatment
Experimental: Cohort 1 (12 to < 18 years of age)

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
Tablet (s) or tablet (s) for oral suspension (if unable to swallow) will be administered orally once daily
Other Name: Vitekta®

Drug: 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.
Experimental: Cohort 2 (6 to < 12 years of age)

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
Tablet (s) or tablet (s) for oral suspension (if unable to swallow) will be administered orally once daily
Other Name: Vitekta®

Drug: 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.
Experimental: Cohort 3 (2 to < 6 years of age)

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
Tablet (s) or tablet (s) for oral suspension (if unable to swallow) will be administered orally once daily
Other Name: Vitekta®

Drug: 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.
Experimental: Cohort 4 (4 weeks to < 2 years of age)

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
Tablet (s) or tablet (s) for oral suspension (if unable to swallow) will be administered orally once daily
Other Name: Vitekta®

Drug: 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.


Outcome Measures
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Primary Outcome Measures :
  1. Pharmacokinetic (PK) Parameter: AUCtau of EVG [ Time Frame: Predose and up to 12 hours postdose on Day 10 ]
    AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

  2. Pharmacokinetic (PK) Parameter: Cmax of EVG at Day 10 [ Time Frame: Predose and up to 12 hours postdose on Day 10 ]
    Cmax is defined as the maximum concentration of drug.

  3. Percentage of Participants Experiencing Treatment-emergent Adverse Events [ Time Frame: 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) ]
  4. Percentage of Participants Experiencing Laboratory Abnormalities [ Time Frame: 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) ]
    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).


Secondary Outcome Measures :
  1. Pharmacokinetic (PK) Parameter: Ctau of EVG [ Time Frame: Predose and up to 12 hours postdose on Day 10 ]
    Ctau is defined as the observed drug concentration at the end of the dosing interval.

  2. Pharmacokinetic (PK) Parameter: CL/F of EVG [ Time Frame: Predose and up to 12 hours postdose on Day 10 ]
    CL/F is defined as the apparent oral clearance following administration of the drug.

  3. Pharmacokinetic (PK) Parameter: Vz/F of EVG [ Time Frame: Predose and up to 12 hours postdose on Day 10 ]
    Vz/F is defined as the apparent volume of distribution of the drug.

  4. Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the FDA Snapshot Algorithm [ Time Frame: Week 24 ]
    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.

  5. Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the FDA Snapshot Algorithm [ Time Frame: Week 48 ]
    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.

  6. Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 24 as Defined by the FDA Snapshot Algorithm [ Time Frame: Week 24 ]
    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.

  7. Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 48 as Defined by the FDA Snapshot Algorithm [ Time Frame: Week 48 ]
    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.

  8. Change From Baseline in Plasma Log₁₀ HIV-1 RNA at Week 24 [ Time Frame: Baseline to Week 24 ]
  9. Change From Baseline in Plasma Log₁₀ HIV-1 RNA at Week 48 [ Time Frame: Baseline to Week 48 ]
  10. Change From Baseline in CD4 Cell Count at Week 24 [ Time Frame: Baseline to Week 24 ]
  11. Change From Baseline in CD4 Cell Count at Week 48 [ Time Frame: Baseline to Week 48 ]
  12. Change From Baseline in CD4 Percentage at Week 24 [ Time Frame: Baseline to Week 24 ]
  13. Change From Baseline in CD4 Percentage at Week 48 [ Time Frame: Baseline to Week 48 ]
  14. Tanner Stage Evaluation by Sex at Week 24 [ Time Frame: 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).

  15. Tanner Stage Evaluation by Sex at Week 48 [ Time Frame: 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).

  16. Age of First Menses [ Time Frame: 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) ]
    Age of first menses for female participants.

  17. Palatability of Oral Suspension Formulation of EVG in Appropriate Age Group [ Time Frame: Up to Week 48 ]
  18. Adherence to EVG [ Time Frame: 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) ]
    Adherence was calculated as the number of pills taken divided by number of pills prescribed multiplied by 100.


Eligibility Criteria
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Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   up to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01923311


Locations
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United States, Colorado
University of Colorado Denver
Aurora, Colorado, United States, 80045
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
Italy
Universita degli Studi di Pavia - Fondazione IRCCS Policlinico San Matteo
Pavia, Italy, 27100
South Africa
Be Part Yoluntu Centre
Cape Town, South Africa, 7646
Rahima Moosa Mother and Child Hopsital
Johannesburg, South Africa, 2112
Spain
Hospital Universitario De Getafe
Getafe, Madrid, Spain, 28095
Hospital 12 de Octubre
Madrid, Spain, 28041
Thailand
Thai Red Cross AIDS Research Centre (HIV-NAT)
Bangkok, Thailand, 10330
Siriraj Hospital
Bangkok, Thailand, 10700
Uganda
Joint Clinical Research Centre
Kampala, Uganda
Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Gilead Study Director Gilead Sciences
  Study Documents (Full-Text)

Documents provided by Gilead Sciences:
Study Protocol  [PDF] April 25, 2013
Statistical Analysis Plan  [PDF] January 12, 2018

More Information
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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01923311     History of Changes
Other Study ID Numbers: GS-US-183-0160
2013-001969-16 ( EudraCT Number )
First Posted: August 15, 2013    Key Record Dates
Results First Posted: July 11, 2018
Last Update Posted: August 9, 2018
Last Verified: July 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Gilead Sciences:
Pediatrics
Adolescents
HIV
HIV-1
Treatment-experienced

Additional relevant MeSH terms:
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HIV Infections
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
 Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immune System Diseases
Slow Virus Diseases
Antiviral Agents
Anti-Infective Agents