| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| 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 |
• Evaluate the effects of belatacept, relative to CsA, on the composite of subject and
graft survival by 12 months
• Evaluate the effects of belatacept, relative to CsA, on the composite of measured
GFR < 60 mL/min/1.73 m2 at Month 12 or a decrease in measured GFR
≥ 10 mL/min/1.73 m2 from Month 3 to Month 12. |
|
| E.2.2 | Secondary objectives of the trial |
•Evaluate the effects of belatacept, relative to CsA, on :
(a) measured GFR at 12;
(b) biopsy-proven CAN at 12 months.
•Assess the effects of belatacept, relative to CsA, on :
(a) the individual components of the primary composite endpoint of measured GFR < 60 mL/min/1.73 m2 at Month 12 or a decrease in measured GFR >= 10 mL/min/1.73 m2 from Month 3 to Month 12;
(b) the triple composite endpoint of death, graft loss, and acute rejection by 12, 24, and 36 months.
(c) the proportion of subjects with a measured GFR < 60 mL/min/1.73 m2 at 24 months.
(d) measured GFR at 3 and 24 months, and change from baseline (3 months) to 12 months and to 24 months.
Please see the protocol for additional secondary and tertiary objectives. |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Exploratory Research Substudy Amendment Number 04 - Site Specific - Selected Sites, dated 16-Feb-06, version 2.
This substudy aims to analyze gene and protein expression patterns as a potential biomarker and to assess the potential of protein and RNA expression patterns for predicting Chronic Allograft Nephropathy (CAN) in renal transplant patients. |
|
| E.3 | Principal inclusion criteria |
1) The subject is willing to provide signed written informed consent;
2) The subject is a first-time recipient of a deceased donor kidney transplant;
3) The donor and/or donor kidney meet at least 1 of the following extended criteria
for organ donation:
a) Donor age >= 60 years
OR
b) Donor age 50 – 59 years and 1 of the following:
(i) Cerebrovascular accident (CVA) + hypertension + SCr > 1.5 mg/dL OR
(ii) CVA + hypertension OR
(iii) CVA + SCr > 1.5 mg/dL OR
(iv) Hypertension + SCr > 1.5 mg/dL
OR
c) Anticipated CIT >= 24 hours (subjects should not be randomized if actual CIT
is < 20 hours)
OR
d) Donor with cardiac death (non-heart beating donor)
4) Men and women, ages 18 and older, inclusive
5) WOCBP must be using an adequate method of contraception to avoid pregnancy
throughout the study and for up to 8 weeks after the study in such a manner that
the risk of pregnancy is minimized.
It should be noted that according to the US product information for mycophenolate mofetil (CellCept®), two reliable forms of contraception must be used simultaneously unless abstinence is the chosen method. |
|
| E.4 | Principal exclusion criteria |
1) WOCBP who are unwilling or unable to use an acceptable method to avoid;
pregnancy for the entire study period and for up to 8 weeks after the last infusion.
2) Women who are pregnant or breastfeeding;
3) Women with a positive pregnancy test on enrollment or prior to study drug administration;
4) Genetically-identical donor recipient pairs (ie, identical twins);
5) Donor age < 10 years;
6) Subjects with underlying renal disease of:
a) Primary focal segmental glomerulosclerosis,
b) Type I or II membranoproliferative glomerulonephritis,
c) Hemolytic uremic syndrome (HUS)/thrombotic thrombocytopenic purpura
syndrome;
If a subject has ESRD of unknown etiology and/or has no histologically-confirmed
diagnosis, the subject may be enrolled into the study as long as there are no clinical signs or symptoms consistent with the clinical diagnosis of primary focal segmental
glomerulosclerosis, Type I or II membranoproliferative glomerulonephritis, or HUS, as
deemed by the investigator.
7) Subjects with current PRA >= 30%;
8) Subjects with a positive T-cell lymphocytotoxic crossmatch;
9) Subjects with any prior solid organ transplant (including kidney);
10) Subjects receiving a concurrent solid organ (heart, liver, pancreas) or cell (islet, bone marrow, stem cell) transplant or subjects deemed likely to have a second solid organ or cell transplant (eg, pancreas or islet transplant) in the next 3 years by the
investigator;
11) Subjects receiving paired kidneys from the extended criteria donor (dual kidney
transplant);
12) Subjects who are hepatitis C antibody-positive or polymerase chain reaction
(PCR)-positive for hepatitis C;
13) Subjects who are hepatitis B surface antigen-positive or PCR-positive for hepatitis B;
14) Subjects with known human immunodeficiency virus (HIV) infection;
15) Subjects with active tuberculosis (TB) requiring treatment within the previous 3 years or any subject who previously required triple (or more) combination therapy for TB. Subjects with a known positive purified protein derivative (PPD) will not be eligible for the study unless they completed treatment for latent TB and have a negative chest x-ray at the time of enrollment. PPD testing done within the last 12 months is acceptable as long as there is documentation of the results. Subjects without a PPD in the last 12 months who have a previous negative result may be enrolled if they also have a negative chest x-ray at enrollment, no symptoms indicative of TB, no known TB contacts, not currently residing in, recently traveled to, or previously immigrated from an area endemic for TB. A PPD response that is >= 10 mm induration or a Heaf score of > 1 in non-Bacille Calmette-Guérin (non-BCG) immunized subjects or > 2 in BCG immunized subjects should be considered a positive test. More conservative criteria may be applied according to the published guidelines and/or local standards endorsed by the medical society;
16) Subjects with any active infection or other contraindication that would normally
exclude transplantation;
17) Subjects whose life expectancy is severely limited by disease state or other
underlying medical condition;
18) Subjects with a history of cancer (other than non-melanoma skin cell cancers cured by local resection) within the last 5 years;
19) Subjects with a history of substance abuse (drug or alcohol) within the past 5 years, or psychotic disorders that are not compatible with adequate study follow-up;
20) Subjects with active peptic ulcer disease, chronic diarrhea, or gastrointestinal
malabsorption;
21) Subjects with laboratory values that meet the following criteria are to be excluded from the study:
Hematology:
- Hemoglobin < 7 g/dL
- Platelets < 80,000/mm3
- White blood cell (WBC) count < 3000/mm3 (3 x 109/L)
Chemistry:
- Bilirubin >1.5 x upper limit of normal range (ULN); Subjects who have Gilbert’s syndrome and have a normal direct bilirubin are permitted
- Aspartate aminotransferase (AST) >= 2 x ULN
- Alanine aminotransferase (ALT) >= 2 x ULN
22) All women 40 years or older and women of any age who have first degree relatives with a history of breast carcinoma or who have other risk factors of breast carcinoma, must have a screening mammogram, or provide results of a screening mammogram performed within 6 months of enrollment.
Please refer to the complete list of criteria in section 5.2. of the protocol. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
•Evaluate the effects of belatacept, relative to CsA, on the composite of subject and graft survival by 12 months.
•Evaluate the effects of belatacept, relative to CsA, on the composite of measured GFR < 60 mL/min/1.73 m2 at Month 12 or a decrease in measured GFR >= 10 mL/min/1.73 m2 from Month 3 to Month 12.
|
|
| 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 | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Exploratory Research Substudy; QoL questionnaire SF-36 |
|
| 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 | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
| Partially-blinded, active-controlled |
|
| 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 | 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 | 35 |
| 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 |
|
| 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 | 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 |
Print
