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 investigate the long-term safety and tolerability of ATC in treatment-experienced HIV-1 infected patients. |
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E.2.2 | Secondary objectives of the trial | |
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. (a) Patients who complete studies AVX-301 or AVX-302 and fulfill the following criteria: - Plasma HIV-1 RNA levels ≤2,000 copies/mL - Patients with plasma HIV-1 RNA levels >2,000 copies/mL should be discussed on an individual basis with the Sponsor. or (b) Patients who meet the criteria for open-label access to ATC because of virologic failure/lack of response in study AVX-301 or AVX-302, and who are withdrawn from those studies for that reason, and who fulfill the following criteria: - Demonstration of presence of M184V/I mutation, and absence of Q151M or 69 insertions, in reverse transcriptase at Screening. Note: Virologic failure is defined as the HIV-1 RNA level increasing by >1.0 log10 copies/mL (confirmed on two separate occasions at least one week apart) from the nadir value recorded during the study. 2. Unrestricted CD4+ cell count. 3. 18 years of age, or older. 4. Male, or non-pregnant, non-breastfeeding female patients, who agree to comply with the applicable contraceptive requirements of the protocol. 5. The patient must understand and be able, willing and likely to fully comply with study procedures and restrictions. 6. 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. Patients enrolled in study AVX-304. 2. Considered unlikely to be ART compliant (OBR or investigational product) by the Investigator. 3. Documented major protocol violation(s) during AVX-301 or AVX-302 including noncompliance with study medication and/or OBR. 4. Prior withdrawal from AVX-301 or AVX-302 for any reason. Patients who wish to withdraw from AVX-301 or AVX-302 and enter AVX-303 on the grounds of protocol-defined virologic failure or lack of response must continue in AVX-301 or AVX-302 until screening for AVX-303 is complete and eligibility confirmed. 5. Patients who have previously been enrolled into this study and subsequently withdrawn. 6. Current acute or chronic hepatitis B virus infection (HBsAg positive and requiring treatment in the next 12 months). a. Previous, resolved HBV infection (HBsAg seronegative with seropositivity for IgG-anti-HBc and/or anti-HBs antibodies) is permitted. b. Well controlled HBV-infected patients not taking tenofovir as part of the OBR who have been receiving adefovir dipivoxil continuously since at least 30 days prior to screening in AVX-301, who meet the requirements for AST and ALT <3 x ULN and who continue to receive adefovir dipivoxil for the duration of the study may be enrolled. 7. Current treatment for hepatitis C virus infection or treatment likely within 12 months. 8. Current or relevant previous history of serious, severe or unstable (acute or progressive) physical or psychiatric illness, any medical disorder that may require treatment or make the patient unlikely to fully complete the study, or any condition that presents undue risk from the investigational product or procedures, as determined by the investigator. Also, any current or recurring disease or intolerance to investigational product that could affect the action, absorption or disposition of the investigational product, or clinical or laboratory assessments, as determined by the Investigator. 9. Clinically relevant abnormalities of medical history, physical examination, or laboratory parameters (hematology, biochemistry, urinalysis). 10. Patients with any of the following abnormal clinical laboratory tests at Screening: a. hemoglobin <10.0g/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. The patient has, in the opinion of the Investigator, a dependence on alcohol or other substance abuse within 6 months of Screening. 12. Active, serious infections (other than HIV-1 infection) requiring parenteral antimicrobial or antiparasitic therapy within 15 days prior to Screening. 13. Female patients with a positive pregnancy test at Screening or Baseline, or who are breastfeeding, or who plan to become pregnant during the duration of the study and any follow up. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is defined as the safety and tolerability of ATC in treatment-experienced HIV-1 infected patients.
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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 | No |
E.8.1.1 | Randomised | No |
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 | 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 | 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 | 15 |
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 | No |
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 | 3 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |