E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects Infected with HIV-1 Who Have Maintained an Adequate Response to ART |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10068341 |
E.1.2 | Term | HIV-1 infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
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 if a re-boost with Vacc-4x could
a) reduce the viral load set-point, and
b) increase the immune response obtained following immunization with Vacc-4x in Study CT-BI Vacc-4x 2007/1 (EudraCT Number 2007-006302-13). |
|
E.2.2 | Secondary objectives of the trial |
• To evaluate the effect of a re-boost with Vacc-4x on CD4 counts and CD8 counts.
• To assesses in vivo immunogenicity of Vacc-4x by evaluation of DTH and to compare the DTH response to the DTH response observed in the initial study; CT-BI Vacc-4x 2007/1
(EudraCT Number 2007-006302-13).
• To evaluate the safety and tolerability of re-boosting with Vacc-4x |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Completed immunization regimen with Vacc-4x active and stopped ART (at Week 28) in the CT-BI Vacc-4x 2007/1 study. (No re-start of ART is required).
2. Documented pre-study CD4 cell count ≥400x10e6/L.
3. Documented pre-study viral load < 300 000 copies/mL.
4. Signed informed consent. |
|
E.4 | Principal exclusion criteria |
1. Reported AIDS-defining illness within the previous year.
2. Malignant disease.
3. On chronic treatment with immune-suppressive therapy.
4. Unacceptable values of the hematologic and clinical chemistry parameters, as judged by the Investigator, including creatinine values >1.5 x upper limit of normal (ULN), and AST, ALT and alkaline phosphatase (ALP) values >2.5 x ULN.
5. Concurrent chronic active infection such as viral hepatitis B or C or tuberculosis.
6. Pregnant or breastfeeding women.
7. Women of childbearing potential not using reliable and adequate contraceptive methods
(defined as: use of oral, implanted, injectable, mechanical or barrier products for the prevention of pregnancy; practicing abstinence; sterile) during the 5 weeks re-boosting
period including the DTH and for 2 weeks after the DTH test, or sexually active male subjects with partners of child bearing potential unwilling to practice effective contraception during the 5 weeks re-boosting period including the DTH and for 12 weeks after the DTH-test.
8. Current participation in other clinical therapeutic studies.
9. Incapability of compliance to treatment protocol, in the opinion of the Investigator |
|
E.5 End points |
E.5.1 | Primary end point(s) |
• Viral load set point (mean of VL count week 25 and 29) for subjects discontinuing ART according to protocol and not resuming ART until week 29 compared to:
- viral load set point* for subjects not resuming ART before week 52 or later in the CT-BI Vacc-4x 2007/1 study and who entered this study, or if week 52 not reached in the previous study
- viral load set point** for subjects resuming ART at the earliest week 40 in the CT-BI Vacc-4x 2007/1 study and who entered this study.
* The VL set point was defined as the mean of VL count week 48 and week 52 week in subjects who did not resume ART.
**The VL set point was defined as the week 40 VL count for subject resuming ART week
40 or the mean of the last two VL counts prior to ART resumption for subjects resuming
ART week 44 or later but before week 52.
Comparison will also be made to pre-ART viral load values, if available from the CT-BI Vacc-4x 2007/1 study.
• T-cell response will be measured by ELISPOT as well as by T-cell proliferative response assay (Flow Cytometry) and intracellular cytokine staining at Week 1 (before re-boosting), Week 5 (two weeks after re-boosting), Week 17, Week 29 and Week 37. These will be compared to the responses reported in the study CT-BI Vacc-4x 2007/1. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
• Viral load set point (mean of VL count week 25 and 29)
• T-cell response will be measured at Week 1 (before re-boosting), Week 5 (two weeks after re-boosting), Week 17, Week 29 and Week 37 |
|
E.5.2 | Secondary end point(s) |
• CD4 counts at Screening, Weeks 1, 3, 5, 13, 17, 21, 25, 29 and 37 (End of Study), absolute numbers of CD4 counts, and treatment emergent changes of CD4 counts from mean of Screening and Week 1.
• Change (and percent change) in CD4 count from Week 13 (discontinue ART) to Weeks 17, 21, 25, 29 and 37.
• CD8 counts at Screening, Weeks 1, 3, 5, 13, 17, 21, 25, 29 and 37 (End of Study), absolute numbers of CD8 counts, and treatment emergent changes of CD8 from mean of Screening and Week 1.
• Change (and percent change) in CD8 count from Week 13 (discontinue ART) to Weeks 17, 21, 25, 29 and 37 (End of Study).
• DTH (both induration and erythema) at Week 1 and Week 5, in terms of observed areas (mm2 length x height) and also in terms of a positive test, defined as an area ≥ 10mm2 DTH-tests, both areas and number of positive tests registered at Week 1 will be compared with the
corresponding values registered at Week 5. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
• CD4 counts at Screening, Weeks 1, 3, 5, 13, 17, 21, 25, 29 and 37 (End of Study
• Change (and percent change) in CD4 count from Week 13 (discontinue ART) to Weeks 17, 21, 25, 29 and 37.
• CD8 counts at Screening, Weeks 1, 3, 5, 13, 17, 21, 25, 29 and 37 (End of Study)
• Change (and percent change) in CD8 count from Week 13 (discontinue ART) to Weeks 17, 21, 25, 29 and 37 (End of Study).
• DTH (both induration and erythema) at Week 1 and Week 5. |
|
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
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 | No |
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 |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 22 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 22 |
E.8.9.2 | In all countries concerned by the trial days | 0 |