E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 10064446 |
E.1.2 | Term | HIV infection WHO clinical stage I |
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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 compare the antiretroviral efficacy of ATC to lamivudine (3TC) in treatment experienced, HIV-1 infected patients with the M184V/I mutation in reverse transcriptase.
•To compare the safety and tolerability of ATC to lamivudine (3TC) in treatment experienced, HIV-1 infected patients.
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E.2.2 | Secondary objectives of the trial |
•To compare the effect of ATC vs. 3TC upon CD4+ and CD8+ T-cell counts.
•To investigate the influence of increasing nucleoside associated mutations (NAMs) in reverse transcriptase upon the antiretroviral efficacy of ATC.
•To investigate the emergence of ATC-associated HIV-1 resistance mutations.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
To be eligible for inclusion, each patient must fulfil each of the following criteria at Screening: 1. 18 years of age, or older. 2. Male, or non-pregnant, non-breastfeeding female patients, who agree to comply with the applicable contraceptive requirements of the protocol 3. Documented laboratory diagnosis of HIV-1 infection (positive ELISA HIV-1 antibody test confirmed by Western Blot, p24 assay, HIV-1 RNA, or culture); if no record exists, must be tested at screening. 4. Currently receiving stable ART regimen comprising at least three drugs, and containing either lamivudine or emtricitabine that is unchanged for at least 2 months prior to first dose of Investigational Product. 5. Plasma HIV-1 RNA levels ≥2,000 copies/mL at Screening using the Roche Cobas Ampliprep / Cobas Taqman (dynamic range 40-10,000,000 copies per mL) performed at the central laboratory. 6. Presence of the M184V/I mutation in reverse transcriptase at Screening. 7. Unrestricted CD4+ cell count. 8. The patient must understand and be able, willing and likely to fully comply with study procedures and restrictions. 9. Written/marked, informed consent to participate in the study prior to the conduct of any study related procedures.
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E.4 | Principal exclusion criteria |
Patients will be excluded from the study if any of the following criteria are met at Screening: 1. Previous documented laboratory diagnosis of HIV-2 infection 2. Presence of Q151M or 69 insertion mutations in reverse transcriptase. 3. Considered to be significantly and chronically ART non-compliant by the Investigator. 4. Current or recurring disease that could affect the action, absorption or disposition of the Investigational Product, or clinical or laboratory assessments, as determined by the investigator. 5. Current acute or chronic Hepatitis B virus infection (HBsAg positive and requiring treatment in the next 12 months). - Previous, resolved HBV infection is permitted. - Well controlled HBV-infected patients not taking tenofovir as part of the OBR and who have been receiving adefovir dipivoxil for at least 30d prior to screening, who meet the requirements for AST and ALT < 3 times upper limit of normal range (ULN) and who continue on adefovir dipivoxil for the duration of the study may be enrolled. Adefovir dipivoxil should not be prescribed concurrently with tenofovir in this study due to concerns over potential renal toxicity. 6. Current treatment for Hepatitis C virus infection or treatment likely during the duration of the study.. 7. Clinically relevant current or recurring disease, illness or laboratory abnormality likely to require treatment during the study that could affect interpretation of efficacy end-points (eg HIV-1 RNA levels), prevent the patient from fully complying with the study, or present undue risk from the Investigational Product or procedures, as determined by the Investigator. 8. A new AIDS-defining condition (defined in Category C, Appendix 1) diagnosed within 42 days prior to the first dose of Investigational Product with the exception of a. CD4 cells <200/mm3 b. Kaposi’s sarcoma (KS) confined to the skin c. HIV-wasting disease ie, wasting not related to any other known cause 9. Patients who, within 42 days prior to the first dose of Investigational Product, have received any of the following: a. immunomodulating agents such as systemic corticosteroids (eg, prednisone or prednisolone exceeding 10mg/day or equivalent dose of any other corticosteroid for more than 7 days), interleukin (IL)-2, IFN-, IFN- or IFN- b. immunization other than for influenza and pneumococcus c. systemic chemotherapeutic agents d. an HIV prophylactic or immunotherapeutic vaccine 10. Patients with any of the following abnormal clinical laboratory tests at Screening: a. Hemoglobin <10.0 g/dL for men and <9.0g/dL for women b. Neutrophil count < 750/mm3 c. Platelet count <50,000/mm3 d. AST or ALT ≥3 times the upper limit of normal (ULN) e. Total bilirubin is >1.5 x ULN, with the exception of patients receiving atazanavir or any other medication known to elevate the indirect bilirubin level as long as the direct bilirubin is less than the ULN. f. Lipase >3 times ULN g. Amylase >3 times ULN (unless serum lipase is 1.5 times ULN) h. Estimated Creatinine Clearance <50mL/min (estimated by Cockcroft and Gault equation) 11. Known or suspected intolerance or hypersensitivity to ATC, lamivudine or any of the stated ingredients 12. The patient has, in the opinion of the Investigator, a dependence on alcohol or other substance abuse within 6 months of Screening that will likely interfere with study compliance and/or make difficult the objective interpretation of clinical and/or laboratory data. 13. Active, serious infections (other than HIV-1 infection) requiring parenteral antimicrobial or antiparasitic therapy within 15 days prior to Screening. 14. Use of another investigational agent or participation in a clinical trial of an investigational agent up to 30 days before Screening. Patients enrolled in non-interventional, observation only studies, whose requirements do not conflict with those of this protocol, are eligible. Patients receiving tipranavir, darunavir, maraviroc, etravirine, or raltegravir through Expanded Access Schemes are eligible for Screening provided the local conditions of expanded access do not conflict with this protocol. Patients receiving other investigational antiretroviral agents may be eligible for Screening upon Sponsor approval, provided the local conditions of expanded access do not conflict with this protocol. Note that the retention or inclusion of Expanded Access agents in the new OBR on Day 0 requires separate approval 15. Female patients with a positive pregnancy test at Screening or Baseline, or who are breastfeeding, or who plan to become pregnant. 16. Patients that have previously been enrolled into this study and subsequently withdrawn. 17. Patients that have previously received treatment with ATC.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is defined as the proportion of patients with plasma HIV-1 RNA <50 copies/mL at W24.
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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 | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 49 |
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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28 days from the last dose of study medication. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |