E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
TREATMENT OF TREATMENT NAÏVE HIV-INFECTED PATIENTS WITH R5 HIV-1 |
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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 | 10020161 |
E.1.2 | Term | HIV infection |
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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 examine if the combination of maraviroc (SelzentryTM, Celsentri®) and atazanavir/ritonavir is effective for the treatment of treatment-naïve HIV-1 infected subjects as measured by the percentage of subjects with HIV-1 RNA below the limits of assay detection (<50 copies of HIV-1 RNA per milliliter of plasma) at 48 weeks. |
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E.2.2 | Secondary objectives of the trial |
1. Safety and tolerability; 2. To assess the viral kinetics within the first 2 weeks in the first 15 patients in each treatment arms (US sites only); 3. To evaluate the pharmacokinetics of maraviroc in a subset of patients (n=15)enrolled in the maraviroc treatment arm (US sites only); 4. To assess virologic response over time; 5. To assess immunological response (CD4 and CD8 counts) over time; 6. To examine the evolution of viral resistance and/or tropism in treatment failure patients only. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
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 trial. 2. At least 16 years of age (or minimum age as determined by local regulatory authorities or as legal requirements dictate) at the Screening Visit. 3. HIV-1 RNA viral load of ≥1,000 copies/mL measured at the Screening Visit. 4. CD4 count ≥100 cells/mm3 at Screening. 5. Have only R5 HIV-1 at Screening as verified by the Monogram Bioscience Trofile assay with enhanced sensitivity. 6. A negative urine pregnancy test at the Baseline Visit, prior to receiving the first dose of study medication, for Women of Child Bearing Potential (WOCBP). 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. 7. Effective barrier contraception for WOCBP. In addition, WOCBP must use another acceptable method of contraception for the duration of the study. Acceptable contraception includes, but is not limited to, oral, implanted or injectable hormone therapy and intrauterine devices. 8. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. |
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E.4 | Principal exclusion criteria |
Subjects presenting with any of the following will not be included in the study: 1. Suspected or documented active, untreated HIV-1 related Opportunistic Infection(OI) or other condition requiring acute therapy (eg, acute hepatitis C virus infection)at the time of Randomization [Patients on a stable (>1 month) secondary OI prophylaxis regimen or chronic treatment with stable disease (eg, for hepatitis C virus infection) are eligible for the study; patients on a primary OI prophylaxis regimen of any duration are also eligible for the study]. 2. Treatment for an active opportunistic infection, or unexplained temperature >38.5 C (101.3º F) for 7 consecutive days, within 30 days prior to Randomization. 3. Prior treatment with any other HIV antiretroviral therapy for more than 14 days at any time. 4. Active alcohol or substance abuse sufficient, in the Investigator’s judgment, to prevent adherence to study medication and/or Follow-Up. 5. Pregnant, breast feeding or planning to become pregnant. 6. Suspected primary (acute) HIV-1 infection. 7. Initiation of therapy with a potentially myelosuppressive, neurotoxic, hepatotoxic and/or cytotoxic agent within 60 days prior to Randomization or the expected need for such therapy during the study period. NOTE: Trimethoprim-sulfamethoxazole may not be initiated within 60 days prior to Randomization but may be continued if the subject is on stable therapy. 8. Malignancy requiring parenteral chemotherapy that must be continued for the duration ofthe trial. 9. Documented or suspected acute hepatitis or pancreatitis within 30 days prior to Randomization. 10. Renal insufficiency defined as a serum creatinine greater than 3 times the upper limit of normal or a creatinine clearance of less than 50 mL/min, as calculated by the Cockcroft and Gault equation. 11. Total bilirubin greater than 2 times the upper limit of normal. Changes of one or more grades in total bilirubin between Screening and the Randomization Visit should be reviewed with the Pfizer Medical Monitor before the initiation of study medication. 12. AST and/or ALT greater than 3 times the upper limit of normal. Changes of one or more grades in LFT results between Screening and Randomization should be reviewed with the Pfizer Medical Monitor before commencing dosing of study medications. 13. Cirrhosis of the liver, moderate or severe hepatic impairment (Child-Pugh classificationB or C). 14. Hepatitis B surface antigen positive. 15. Absolute neutrophil count ≤750 cells/mm3. 16. Platelet count≤ 50,000 cells/mm3. 17. Hemoglobin ≤7 g/dLl. 18. Clinically significant malabsorption syndrome (eg, ≥6 loose stools per day for at least 7 consecutive days) within 30 days prior to Randomization. 19. Inability to tolerate oral medication. 20. Concomitant therapy with other investigational agents. 21. Contraindicated medications being taken by the subject at the time of Randomization that must be continued during the study period, including immunomodulators (for the treatment of HIV-1 infection;), and any contraindicated medication described in the package inserts of maraviroc (Selzentry, Celsentri), atazanavir (Reyataz), ritonavir (Norvir) and emtricitabine/tenofovir (Truvada). 22. Any evidence of resistance to atazanavir, tenofovir, and emtricitabine. 23. X4-or dual/mixed-tropic virus by enhanced Trofile assay or repeated assay failure or not reportable results. 24. 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. 25. Potentially life threatening (Grade 4) laboratory abnormality or medical condition (according to the Division of AIDS table for grading severity of adult adverse experiences). Subjects with Grade 4 triglyceride, cholesterol or CPK elevations will be eligible for this study. 26. Have a known hypersensitivity to atazanavir, ritonavir, tenofovir, emtricitabine, to peanut and to maraviroc or any of its excipients, including soy lecithin or dyes of those drugs as described in the package inserts. 27. Participation in other studies before the current study begins and/or during study participation. 28. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The percentage of patients with plasma HIV-1 RNA <50 copies/mL in each treatment arm at 48 weeks. |
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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 | No |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
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) | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 23 |
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 |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 20 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 20 |