E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
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 change from baseline in CD4+ T lymphocyte count after 32 weeks in groups of participants randomly assigned to receive no therapy (no antiretrovirals or rIL-2), subcutaneous rIL-2 monotherapy or subcutaneous rIL-2 with pericycle HAART. |
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E.2.2 | Secondary objectives of the trial |
To compare among the three treatment groups after 32 weeks: 1. incidence of grade 3 and 4 events . 2. number of therapy modifications . 3. mean plasma HIV RNA changes from baseline (evaluated at 32 weeks and 12 months). 4. mean CD4+ T lymphocyte changes from baseline at 12 months. 5. changes in HIV genotyping that may represent development of antiretroviral drug resistance. 6. selected lipid, thyroid, and hepatic abnormalities. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Documented HIV-1 infection by any licensed ELISA test and confirmed by a second method (e.g., Western Blot); or any one of the following prior to randomization: detectable HIV p24 antigen, quantifiable plasma HIV RNA, or proviral DNA. 2. ≥ 18 years of age (children are not eligible for study participation because data on rIL-2 in pediatric HIV disease is limited, and more data on the effects of rIL-2 in the absence of antiretrovirals should be gathered in adults before exposing pediatric patients to these risks). 3. The following clinical laboratories obtained within 45 days before randomization: a. One CD4+ T cell count ≥ 300 cells/mm3 (For participants who are status post-splenectomy, also a CD4+ cell percentage on this occasion ≥ 20%). b. AST or ALT < 5 X the upper limit of normal (ULN) range. c. Total or direct bilirubin ≤ 2 X ULN (Participants with hyperbilirubinemia due to Gilbert’s syndrome may have a serum bilirubin up to 5 X ULN). d. Serum creatinine ≤ 2 mg/dl (177 µmol/L). e. Sodium within normal limits. f. Granulocyte count ≥ 1000/mm3. g. Hemoglobin ≥ 10 gm/dl. h. Platelet count ≥ 50,000 cells/mm3. 4. Ability to provide informed consent. 5. Ability to obtain HAART regimens consisting of ≥ 1 protease inhibitor and ≥ 2 nucleoside or nucleotide reverse transcriptase inhibitors. |
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E.4 | Principal exclusion criteria |
1. Any prior history of rIL-2 use 2. Use of any approved or experime.ntal antiretroviral drug (including hydroxyurea) within one year prior to randomization. 3. In the judgment of the clinician, any current indication for continuous antiretroviral therapy, or any contraindication to antiretroviral therapy. 4. Evidence of virological failure on a protease inhibitor or nonnucleoside reverse transcriptase - based antiretroviral regimen. 5. Use of systemic corticosteroids, chemotherapy, or experimental cytotoxic drugs within 45 days prior to randomization. 6. Use of any agent (approved or experimental) with clinically significant immunomodulatory effects within 8 weeks prior to randomization. 7. History of any AIDS-defining illness (category C., CDC, 1993) or any of the following conditions: extrapulmonary Pneumocystis carinii disease; multi-dermatomal Herpes zoster (≥ 10 lesions in a non-contiguous site); American trypanosomiasis (Chagas disease) of the CNS; Penicillium marneffii disease; visceral leishmaniasis; non-Hodgkin’s lymphoma of any cell-type; Hodgkin’s lymphoma; bartonellosis; microsporidiosis (> 1 month’s duration); nocardiosis; invasive aspergillosis; or Rhodococcus equi disease. 8. Concurrent malignancy requiring cytotoxic chemotherapy. 9. Any CNS abnormality that requires ongoing treatment with antiseizure medication. 10. Current or historical autoimmune/inflammatory diseases including: a. Inflammatory bowel disease b. Psoriasis c. Optic neuritis d. Any autoimmune/inflammatory diseases with potentially life-threatening complications 11. Significant cardiac, pulmonary, renal, hepatic, gastrointestinal, CNS, or psychiatric disease or illicit substance use/abuse that in the opinion of the investigator would make the participant a poor candidate for study participation. 12. Pregnancy (for women of childbearing potential, a negative pregnancy test, urine or serum, is required within 14 days prior to randomization). 13. Breastfeeding. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint will be mean change in CD4+ T lymphocyte count from baseline (average of two pre-randomization counts) to 32 weeks in the three study groups. |
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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 | 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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
no therapy (no antiretrovirals or IL-2) |
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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 | 32 |
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
|
A common closing date for all patients will be 12 months after the last participant is randomized (the average follow-up will be 18 months). |
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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 |