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 | Classification code | 10020161 |
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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 evaluate the induction strategy of HAART alone (I1) compared to enfuvirtide (90 mg s.c.BID) in combination with HAART (ENF+HAART, I2) • To determine the overall induction/maintenance treatment strategy (with or without continued ENF) after 48 weeks of treatment • To compare different maintenance strategies for those patients who are qualified for entering the maintenance phase (M1, M2 and M3) • To assess the safety of induction phase (I1 vs I2) and maintenance phase (M1, M2, and M3).
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. HIV-1 infected adults ( > 18 years of age) previously treated with 2 or 3 different ARV classes with a CD4 lymphocyte count ≥200 cells/mm3 and HIV-1 RNA ≥ 1,000 copies/mL, while on their current “pre-study”ARV regimen
2. Must currently be on ARV therapy, with no changes to that regimen for > 4 weeks prior to entering screening (patients on treatment interruption excluded). Patients must remain on their “pre-study”regimen unchanged except for toxicity management until BL1
3. Must be able to create a study HAART regimen with at least 2 ARVs to which his/her virus show sensitivity by genotypic testing at screening (Genotypic Sensitivity Score or GSS ≥2).
4. Must be willing and able to give written informed consent
5. Must be willing and able to abide by the conditions of the protocol, including the possibility of being randomized to HAART or ENF+HAART as described in the Induction Phase as well as possibly being randomized to either stop or continue ENF in the Maintenance Phase
6. Female subjects of childbearing potential must have a negative serum pregnancy test documented during screening for eligibility, and a negative urine pregnancy test within 24 hours prior to first dose of study medication. Female subjects of childbearing potential must agree to use a reliable form of effective barrier contraception (< 1% failure rate) for the duration of the study, and for 30 days after the last dose of study drug, or have documented sterility
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E.4 | Principal exclusion criteria |
1. Expected systemic hypersensitivity to enfuvirtide or to any of the excipients of the investigational medicinal product. 2. History of prior use of enfuvirtide and/or T-1249 3. Patients for whom standard of care, in the judgment of the investigator, would require immediate use of enfuvirtide or medications not permitted in the protocol. 4. Patients on treatment interruption or patients interrupting ARV therapy within 4 weeks of screening or during the screening period for reasons other than toxicity management. 5. Female subjects who are pregnant, breastfeeding, or who plan to become pregnant during the study. 6. Any current clinical parameter of ACTG Grade 3 or laboratory parameter of ACTG Grade 4. Stable current clinical parameter of ACTG Grade 3 or Asymptomatic Grade 4 laboratory abnormalities will be permitted, at the discretion of the investigator (and following approval by the sponsor), if deemed clinically appropriate. 7. Evidence of alcohol and/or drug (illicit or prescription) abuse within one year of entry that, in the judgment of the investigator, would result in the subject being unreliable in fulfilling the conditions of the protocol. 8. Prior non-adherence to antiretroviral treatment regimens that, in the judgment of the investigator, would result in the subject being unreliable in fulfilling the conditions of the protocol. 9. Inability to self-inject enfuvirtide as indicated in the protocol unless a care giver or partner/family member is available to be trained and to administer the injections for the duration of the study. 10. Current severe illness or any other conditions which would make the subject, in the opinion of the investigator, unsuitable for the study. 11. Major organ allograft. 12. Evidence of active, untreated opportunistic infection (including any abnormality on fundoscopic examination, unless deemed benign by an ophthalmologist), or unexplained temperature which is greater than or equal to 38.5 degrees C for seven consecutive days, within 30 days prior to the screening visit. Subjects who are on a stable anti-infective treatment or prophylaxis regimen are allowed in the study. 13. Currently taking or anticipated to take during the course of the study, any immunomodulator, HIV vaccine, or investigational agent for any conditions other than HIV/AIDS.
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E.5 End points |
E.5.1 | Primary end point(s) |
The following two endpoints will be used to assess the virological response at week 24: • Percent of patients initially achieving viral suppression to < 50 copies/mL or • Percent of patients initially achieving viral suppression to < 400 copies/mL. In order to compare how soon patients will respond to the randomized treatment, the time to achieving initial viral suppression to < 50 copies/mL at week 24 will be used. For analyzing continuous endpoints: • Change from baseline in log10 (HIV-1 RNA) at week 24 or • Change from baseline in CD4 counts at week 24. At week 48: In order to compare induction/maintenance strategies for patients with or without continued ENF in their treatment regimen, the percent of patients achieving viral suppression < 50 copies/mL prior to or at week 48 will be used. For comparison of maintenance strategies, the time-to-loss virological response (i.e. 2 consecutive viral load values ≥ 50 copies/mL) will be the primary efficacy endpoint. Safety assessment will be based on comparison of the number and percent of patients that have specified events (pneumonias, SAEs and serious SAEs) during each of the treatment phases. |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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 | 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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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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End of Trial is defined as the date of the last visit /last patient, however exceptions should be justified. |
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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 | |
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 | 0 |