| 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 at 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 measured GFR at 12 months
• Evaluate the effects of belatacept, relative to CsA, on biopsy-proven CAN by 12
months.
• Assess the effects of belatacept, relative to CsA, on calculated GFR at 3, 12, 24, and 36 months, and change from baseline (3 months) to 12, 24, and 36 months
• Assess the effects of belatacept, relative to CsA, on PTDM at 12, 24, and 36 months
• Assess the effects of belatacept, relative to CsA, on measures of hypertension at 12, 24, and 36 months, including SBP and DBP, incidence and prevalence of
hypertension and controlled hypertension, and intensity of treatment regimen.
Please see the protocol for additional secondary and tertiary objectives. |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| 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:
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) CIT < 24 hours, donor age > 10 years
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.
6) Men must use an adequate method of contraception throughout the study, and for up to 8 weeks after the last infusion, so that the risk of pregnancy to their partners is minimized. |
|
| 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 or with a positive pregnancy test on enrollment or prior to study drug administration
3) Males unwilling or unable to use an adequate method of contraception for the entire study period and for up to 8 weeks after the last infusion of study medication.
4) Donor age < 10 years
5) Subjects with underlying renal disease of:
a) Focal segmental glomerulosclerosis (biopsy proven)
b) Type I or II membranoproliferative glomerulonephritis
c) Hemolytic uremic syndrome/thrombotic thrombocytopenic purpura syndrome
6) Subjects with current PRA ≥ 30%
7) Subjects with a positive T-cell lymphocytotoxic crossmatch
8) Subjects with any prior solid organ transplant (including kidney)
9) Subjects receiving a concurrent solid organ (heart, liver, pancreas) or cell (islet, bone marrow, stem cell) transplant
10) Subjects receiving paired kidneys from the extended criteria donor (dual kidney
transplant)
11) Subjects who are hepatitis C antibody-positive or polymerase chain reaction
(PCR)-positive for hepatitis C
12) Subjects who are hepatitis B surface antigen-positive or PCR-positive for hepatitis B
13) Subjects with known human immunodeficiency virus (HIV) infection.
14) 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
15) Subjects with any active infection or other contraindication that would normally exclude transplantation
16) Subjects whose life expectancy is severely limited by disease state or other
underlying medical condition
17) Subjects with a history of cancer (other than non-melanoma skin cell cancers cured by local resection) within the last 5 years
18) 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
19) Subjects with active peptic ulcer disease, chronic diarrhea, or gastrointestinal
malabsorption
20) Subjects with local laboratory values that are Common Toxicity Criteria (CTC)
Grade II or greater (Appendix 2) may not participate in the study. However, certain
specified laboratory parameters that are exceptions to CTC Grade II will be allowed.
See protocol section 5.2 for allowances.
21) 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. Subjects with a mammogram that is suspicious for malignancy and in whom the possibility of malignancy cannot be
reasonably excluded following additional clinical, laboratory, or other diagnostic
evaluations will be excluded. If the screening mammogram was not performed within
6 months of enrollment, but the subject is deemed a suitable transplant candidate by
local criteria, the baseline mammogram may be obtained within 4 weeks after
transplant
22) Subjects who have difficult i.v. access or other reasons that would likely preclude
assessment of the co-primary endpoint of measured GFR or subjects that are unlikely
(eg, due to preexisting coagulation issues) or unwilling to undergo the protocol
specified 12-month allograft biopsy
23) Subjects with a history of true allergy to i.v. iodinated x-ray contrast agents
24) Subjects who have used any investigational drug within 30 days prior to the Day 1 visit
25) Subjects previously treated with belatacept
26) Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (eg, infectious disease) illness must not be enrolled into this study.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary efficacy outcome measures will compare each belatacept-based regimens to a CsA based immunosuppressive regimen on:
• Death or graft loss at 12 months.
• The composite of measured GFR < 60mL/min at Month 12 or a decrease of GFR ≥10mL/min 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 | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Yes |
| 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) | 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.8.5 | 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 |
|
| 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
| |
| 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 | |
| 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 |
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