| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| HIV-1 treatment in combination with other agents. |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10020444 |
| E.1.2 | Term | Human immunodeficiency virus type |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| - 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; - To determine the safety and tolerability of maraviroc in HIV-1 infected children and adolescents. |
|
| E.2.2 | Secondary objectives of the trial |
| - Describe the efficacy of multiple dose administration of maraviroc in treatmentexperienced children infected with CCR5 tropic HIV-1; - Describe tropism changes over time. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| 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. |
|
| E.4 | Principal exclusion criteria |
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>38.5C 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 Trofile TM 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 gastrostomy tube). |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| - Pharmacokinetics: Maraviroc PK parameter, average concentration (Cavg); - Safety: Adverse events >/=Grade 3, Treatment discontinuation secondary to SAEs related to study drug. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Yes |
| E.7.1.1 | First administration to humans | Yes |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| - same IMP used at different dosage |
|
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 19 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 6 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
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