| 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.
• Evaluate the effects of belatacept, relative to CsA, on the incidence of acute rejection by 12 months.
Protocol Amendment 12 - Long-Term Extension:
assess the long term safety and tolerability of belatacept in subjects who have received a kidney transplant, completed the Short Term (36 months of treatment in the main study) and remain on study therapy. |
|
| 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 at 12
months.
• Assess the effects of belatacept, relative to CsA, on 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
• Assess the effects of belatacept, relative to CsA, on the triple composite endpoint of death, graft loss, and acute rejection by 12, 24, and 36 months.
• Assess the overall safety of belatacept, relative to CsA.
Please see the protocol for additional secondary and tertiary objectives.
+ Additional assessments as per Protocol Amendment 09 - Long-Term Extension (See Protocol Appendix 05, section 2.2) |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1) The subject is willing to provide signed written informed consent.
2) The subject is a recipient of a living donor or deceased donor kidney transplant
with an anticipated CIT < 24 hours.
3) Men and women, ages 18 and older, inclusive.
4) 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.
WOCBP must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or
equivalent units of human chorionic gonadotropin [HCG]) within 72 hours prior to the
start of study medication.
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.
Inclusion criteria for participation in Protocol Amendment 09 - Long-Term Extension:
6) Subjects must be willing to participate and provide signed, written informed consent for this long term extension phase.
7) Subjects must have completed 3 years in the IM103008 study (through Month 36) and remained on study treatment (belatacept or cyclosporine)
8) Subjects must be willing and able to continue therapy with MMF. If a subject is unable to tolerate therapeutic doses of MMF, another adjuvant agent may be substituted as described in Section 6.2.6.2.
9) 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) 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
5) Donor age < 10 years
6) Subjects receiving and extended criteria donor organ as defined by:
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
OR
d) Donor with cardiac death (non-heart beating donor)
7) 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
8) Subjects undergoing primary (first-time) transplant with a current PRA ≥ 50%, or subjects undergoing retransplantation with a PRA ≥ 30%.
9) Subjects with previous graft loss due to acute rejection.
10) Subjects with a positive T-cell lymphocytotoxic cross match.
11) Subjects with prior non-renal solid organ transplant (subjects undergoing kidney retransplantation are eligible pending other study criteria being met), or subjects undergoing multi-organ transplants (eg, kidney-pancreas) 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.
12) Subjects receiving a concurrent solid organ (heart, liver, pancreas) or cell (islet, bone marrow, stem cell) transplant.
13) Subjects receiving paired kidneys (dual or en bloc kidney transplants).
14) Subjects who are/whose allograft donor was known hepatitis C antibody-positive or polymerase chain reaction (PCR)-positive for hepatitis C
15) Subjects who are/whose allograft donor was known hepatitis B surface antigen-positive or PCR-positive for hepatitis B
16) Subjects and recipients of a graft from a donor with known HIV infection
17) Subjects at risk for tuberculosis (TB). Specifically, subjects who:
a) Have current clinical, radiographic or laboratory evidence of active or latent TB
b) Have a history of active TB (see Protocol)
c) In the opinion of the investigator, a risk of reactivation of TB that precludes the use of conventional immunosuppression.
18) Subjects with any active infection or other contraindication that would normally exclude transplantation.
19) Subjects whose life expectancy is severely limited by disease state or other underlying medical condition.
20) Subjects with a history of cancer (other than non-melanoma skin cell cancers cured by local resection) within the last 5 years.
21) 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 followup 22) Subjects with active peptic ulcer disease, chronic diarrhea, or gastrointestinal malabsorption.
23) 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
24) All women ≥ 40 years 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.
25) 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.
26) Subjects with a history of true allergy to iodinated x-ray contrast agents.
27) Subjects currently receiving immunosuppressive agent(s) (eg, methotrexate, infliximab, etanercept, etc) for other indications, such as an autoimmune disease, or subjects with comorbidities that treatment with such agents are likely during the trial.
28) Subjects who have used any investigational drug within 30 days prior to the Day 1 visit.
29) Subjects previously treated with belatacept.
30) 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.
+ For participation to Protocol Amendment 09 (LTE), see Protocol Appendix 5, section 5.2
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary efficacy outcome measures will compare each belatacept-based regimen to the CsA-based regimen on:
(1) the composite of subject and graft survival by 12 months;
(2) 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;
(3) the incidence of acute rejection by 12 months.
The primary outcome measures will also be analyzed at Months 24 and 36. The preservation of renal function at Months 24 and 36 will be primarily assessed by the proportion of subjects with a measured GFR < 60 mL/min/1.73 m2 at 24 months and calculated GFR<60mL/min/1.73 m2 at Month 36.
Protocol Amendment 09 - Long-Term Extension:
Assess the ongoing safety and tolerability of belatacept in subjects who have received a renal allograft.
|
|
| 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 | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | Yes |
| 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 | 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 | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 37 |
| 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
|
| The long-term extension will continue until belatacept is marketed in the country where subjects are enrolled or until the study is changed to another study type (e.g. named patient study) or until BMS terminates the development of belatacept in this indication, whichever comes first. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| 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 | 4 |
| 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
