AN OPEN-LABEL, MULTICENTER, MULTIPLE-DOSE PHARMACOKINETIC AND 48-WEEK SAFETY AND EFFICACY TRIAL OF MARAVIROC IN COMBINATION WITH OPTIMIZED BACKGROUND THERAPY FOR THE TREATMENT OF ANTIRETROVIRAL-EXPERIENCED CCR5-TROPIC HIV-1 INFECTED CHILDREN 2-18 YEARS OF AGE
- Conditions
- HIV TreatmentMedDRA version: 9.1Level: LLTClassification code 10020161Term: HIV infection
- Registration Number
- EUCTR2008-006873-33-FR
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 125
Subjects must meet all of the following inclusion criteria to be eligible for enrollment
into the study:
1. Provide a signed and dated written Informed Consent Document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study;
2. Subjects 2-18 years of age available for follow-up period of at least 48 weeks;
3. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures;
4. HIV-1 RNA =1,000 copies/mL measured by Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 Test;
5. Stable pre-study ARV regimen for at least 4 weeks prior to Screening Visit or no pre-study ARV regimen for at least 4 weeks prior to Screening Visit:
? If already receiving ARV therapy prior to Screening Visit, component ARV drugs must not be changed in the prior 4-week period. However, change in dose (for weight gain) or change in formulation of ARV drug is allowed. Subjects will be required to remain on their existing regimen during the Screening period.
? Subjects with unchanged ARV regimen for at least 4 weeks prior to Screening and experiencing virologic failure (defined as plasma HIV-1 RNA =1,000 copies/mL).
6. Experience/intolerance ?6 months (sequential or cumulative) with at least 2 ARV drug classes;
7. Willing to remain on treatment without any changes or additions to OBT regimen, except for toxicity management or upon meeting criteria for virologic failure;
8. For Women of Child Bearing Potential (WOCBP), a negative urine pregnancy test at the Baseline Visit, prior to receiving the first dose of study medication.
NOTE: WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization or is not post-menopausal (ie, no menstrual periods for at least 2 years). Even women who are using oral, implanted or injectable contraceptive hormones or mechanical products (intrauterine devices; barrier methods: eg, condom or diaphragm with spermicide) to prevent pregnancy, who are practicing abstinence, or who have a partner that is sterile (eg, vasectomy), should be considered to be of child bearing potential.
9. Effective barrier contraception for WOCBP and males. In addition, WOCBP must use another acceptable method of contraception for the duration of the study and up to 28 days following the last maraviroc dose. Acceptable contraception includes, but is not limited to, oral, implanted or injectable hormone therapy and intrauterine devices.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
Subjects presenting with any of the following will not be included in the study:
1. Subjects requiring treatment with more than 5 ARV agents in OBT regimen (low dose ritonavir is not considered a separate ARV agent);
2. Prior treatment with maraviroc, another CCR5 antagonist or another experimental HIV entry inhibitor for more than 14 days;
3. History of poor adherence with medication, active alcohol or substance abuse sufficient to prevent adherence to study medication and/or Follow-Up;
4. Current systemic chemotherapy or history of malignancy;
5. Lactating women or planned pregnancy during the trial period;
6. Suspected or documented active, untreated HIV-1 related opportunistic infection or other condition requiring acute therapy (eg, Hepatitis C virus infection) at Baseline Visit;
NOTE: Subjects on stable (>1 month) secondary OI prophylaxis regimen or chronic treatment (eg, Hepatitis C) are eligible for the study. Subjects on primary OI prophylaxis regimen of any duration are also eligible for the study;
7. Treatment for an active opportunistic infection, or unexplained T>38.5°C for 7 consecutive days, within 30 days prior to Baseline Visit;
8. Known hypersensitivity or history of allergy to any component of maraviroc, including soy lecithin or peanuts;
9. Initiating therapy with a potentially myelosuppressive, neurotoxic, hepatotoxic and/or cytotoxic agent within 60 days prior to Baseline, or the expected need for such therapy during the study period;
10. Documented or suspected acute hepatitis or pancreatitis within 30 days prior to Baseline Visit;
11. Known =Grade 3 of any of the following laboratory tests at Screening or within 30 days prior to Baseline Visit:
? Neutrophil count, hemoglobin, platelets, AST, ALT, and creatinine, lipase; NOTE: Subjects with a change of two or more grades in AST or ALT between Screening and Baseline Visits must be reviewed by Pfizer.
? Total bilirubin = Grade 3, unless ALL of the following are true:
? Current regimen includes atazanavir;
? ALT/AST = 2.5 X ULN;
? No symptoms other than jaundice or icterus.
NOTE: Subjects with a change of two or more grades in direct bilirubin between Screening and Baseline Visits must be reviewed by Pfizer.
? Other laboratory values = Grade 3, must be reviewed by Pfizer.
12. History of lactic acidosis within the 3 months prior to Screening. Lactic acidosis defined as:
? Either confirmed lactate =2 X ULN in subjects with ALT and AST values >2.5 X ULN without easily discernable etiology (eg, acute Hepatitis A, B, C or chronic Hepatitis B or C); OR
? New and persistent, otherwise unexplained nausea, vomiting, abdominal pain,
abdominal distention, unexplained fatigue, and dyspnea.
13. Cirrhosis of the liver;
14. Clinically significant malabsorption syndrome (>6 loose stools per day, for at least 7 consecutive days) within 30 days prior to Baseline;
15. X4- or dual/mixed-tropic virus detected by the TrofileTM viral tropism assay or repeated assay failure;
16. Concomitant therapy with other investigational agents (other than experimental
ARV agents available through pre-approval access programs);
17. Contraindicated medications that must be continued during the study period;
18. Any safety, behavioral, clinical, or administrative reasons that in the Investigator’s judgment would potentially compromise study compliance or the ability to evaluate safety/efficacy;
19. Use of gastrostomy tube for administration of maraviroc. (Other medications may be given through the gastro
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: ? To determine the pharmacokinetic profile(s) and dosing schedule(s) for maraviroc in treatment experienced HIV-1 infected children and adolescents on different background therapies;<br>? To determine the safety and tolerability of maraviroc in HIV-1 infected children and adolescents.;Secondary Objective: ? Describe the efficacy of multiple dose administration of maraviroc in treatment experienced children infected with CCR5 tropic HIV-1;<br>? Describe tropism changes over time.;Primary end point(s): ? Pharmacokinetics: Maraviroc PK parameter, average concentration (Cavg);<br>? Safety: Adverse events =Grade 3, Treatment discontinuation secondary to SAEs<br>related to study drug.
- Secondary Outcome Measures
Name Time Method