| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Subjects receiving a kidney transplant from a living donor or a deceased donor.
Pacientes que reciben un trasplante renal de donante vivo o cadaver |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10038533 |
| E.1.2 | Term | Renal transplant |
|
| 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 |
| The primary objective is to assess the rate of AR in different corticosteroid-free belatacept-based immunosuppressive regimens in de novo renal transplant subjects by 6 months post-transplantation. |
|
| E.2.2 | Secondary objectives of the trial |
Secondary objectives will assess the following effects in the corticosteroid-free belatacept arms:
• Severity, treatment, and outcome of AR by 6 months
• Incidence of death and graft loss by 12 months
• Incidence, severity, treatment, and outcome of AR by 12 months
• Incidence of AR, death, and graft loss by 6 and 12 months
• Incidence of metabolic and cardiovascular comorbidity (post-transplant diabetes mellitus [PTDM], dyslipidemias, hypertension) by 12 months
• Renal function (calculated GFR) at 12 months
• Proportion of subjects that remain corticosteroid-free at 12 months
• Incidence of discontinuation of study treatment by 12 months
• Overall safety of a belatacept-based corticosteroid-free immunosuppressive regimen
For exploratory objectives see Protocol Section 2.3. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1) Signed Written Informed Consent
2) Target Population
a) The subject must be a recipient of a renal allograft from a living donor or a deceased donor
b) The subject will have reliable i.v. access
3) Age and Sex
a) Men and women, ages 18 to 70 years, inclusive
b) Women of childbearing potential (WOCBP) must be using an adequate method of
contraception to avoid pregnancy throughout the study [and for up to 8 weeks after the last dose of investigational product] in such a manner that the risk of pregnancy is minimized. |
|
| E.4 | Principal exclusion criteria |
1) Sex and Reproductive Status
a) 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 dose of investigational product]
b) WOCBP using a prohibited contraceptive method
c) Women who are pregnant or breastfeeding
d) Women with a positive pregnancy test on enrollment or prior to investigational product administration
2) Target Disease Exceptions
a) Donor Exceptions:
1) Donor age < 10 years or > 60 years
2) Donor with cardiac death
3) Cold ischemia time ≥ 24 hours
4) Donors who are known hepatitis C antibody-positive or PCR positive for hepatitis C
5) Donors who are known hepatitis B surface antigen-positive or PCR positive for hepatitis B
6) Donors with known HIV infection
b) Recipient Exceptions:
1) Genetically identical donor recipient pairs
2) Recipients whose serology is negative for EBV
3) Subjects with underlying renal disease of:
− Primary focal segmental glomerulosclerosis
− Type I or II membranoproliferative glomerulonephritis
− 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 determined by the investigator
4) Subjects undergoing primary renal transplant with current PRA ≥ 50% or subjects undergoing retransplantation with a PRA > 30%
5) Subjects with previous graft loss due to AR
6) Subjects with a positive T-cell or B-cell crossmatch
7) Subjects with prior non-renal solid organ transplant (SOT) (subjects undergoing kidney retransplantation are eligible assuming other study criteria are met), or subjects deemed likely to have a second SOT or cell transplant in next 12 months
8) Subjects receiving a concurrent SOT or cell transplant
9) Subjects receiving paired kidneys
3) Medical History and Concurrent Diseases
a) Subjects who are known hepatitis C antibody-positive or PCR-positive for hepatitis C
b) Subjects who are known hepatitis B surface antigen-positive or PCR-positive for hepatitis B
c) Subjects with known HIV infection
d) Subjects with a chest radiograph consistent with an acute lung parenchymal process and malignancy.
e) Subjects at risk for tuberculosis (TB). Specifically, subjects:
1) With current clinical, radiographic, or laboratory evidence of active or latent TB as determined by local standard of care.
2) With history of active TB:
- Within the last 2 years, even if it was treated
- Greater than 2 years ago, unless there is documentation of adequate treatment according to locally accepted clinical practice
3) In the opinion of the investigator and based upon appropriate evaluation, a subject whose risk of reactivation of TB precludes administration of conventional immunosuppression
f) Subjects with any significant infection or other contraindication that would normally preclude transplantation
g) Subjects whose life expectancy is severely limited by disease state or other underlying medical condition
h) Subjects with a history of cancer within the last 5 years
i) Subjects with a history of drug or alcohol abuse within the past 5 years, or psychotic disorders that are not compatible with adequate study followup
j) Subjects with active peptic ulcer disease, chronic diarrhea, or gastrointestinal malabsorption
4) Physical and Laboratory Test Findings
a) Body mass index > 35 kg/m2
b) Subjects with laboratory values that meet the following criteria:
1) Hematology:
− Hemoglobin < 7 g/dL
− Platelets < 80,000/mm3
− White blood cell (WBC) count < 3000/mm3 (3 x 109/L)
2) 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
c) 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.
5) Allergies and Adverse Drug Reactions
a) Hypersensitivity to any medications that will be used in the protocol
6) Prohibited Treatments and/or Therapies
a) Subjects who have used any investigational drug within 30 days prior to Day 1
b) Subjects previously treated with belatacept
c) Immunosuppressive therapy within 1 year prior to enrollment. Specifically, subjects may not be taking or have taken CsA, tacrolimus, sirolimus, azathioprine, MMF/MPA, cyclophosphamide, methotrexate, or any lymphocyte-depleting agents
d) Subjects who are on corticosteroids at the time of transplant or require maintenance corticosteroids
7) Prisoners or subjects who are compulsorily detained |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary Efficacy Outcome Measures:
• Incidence of AR by 6 months post-transplant.
Secondary Outcome Measures:
• Severity, treatment, and outcome of AR by 6 months
• Incidence of death and graft loss by 12 months
• Incidence, severity, treatment, and outcome of AR by 12 months
• Incidence of AR, death, and graft loss by 6 and 12 months
• Incidence of metabolic and cardiovascular comorbidity (post-transplant diabetes mellitus, dyslipidemias, hypertension) by 12 months
• Renal function (calculated glomerular filtration rate) at 12 months
• Proportion of subjects that remain corticosteroid-free at 12 months
• Incidence of discontinuation of study treatment by 12 months
• Overall safety of a belatacept-based corticosteroid-free immunosuppressive regimen. |
|
| 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 | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| 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, Immunogenicity and OR assessments |
|
| 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) | 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) | 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 | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 4 |
| 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 | 2 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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