| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Renal transplantation |
| Trapianto di rene |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10038533 |
| E.1.2 | Term | Renal transplant |
| E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
|
| 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. |
| Valutare l`effetto del belatacept rispetto alla ciclosporina sulla sopravvivenza del soggetto e dell`organo trapiantato a 12 mesi; valutare il gfr al 12° mese; valutare l`incidenza del rigetto nei 12 mesi. Emendamento al protocollo numero 12 - Long term extension: Lo scopo di questa fase a lungo termine dello studio consiste nell`ottenere ulteriori informazioni sulla sicurezza e tollerabilita` del Belatacept nei pazienti che hanno completato la fase short term (cioe` che hanno completato i 36 mesi di trattamento dello studio principale) e che continueranno il trattamento. |
|
| 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 12months. 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. |
| valut gli effetti del belatacept rispetto alla ciclosporina delcan bioptico a 12 mesi;valut gli effetti del belatacept rispettoalla ciclosporina della misura del gfr a 12 mesi;valutare gli effetti delbelatacept rispetto alla ciclosporina del gfr <60ml/min/1.73m2 a 12 mesi ouna diminuzione del gfr di >=10ml/min/1.73m2 dal mese 3 al mese 12; valutare glieffetti del belatacept rispetto alla ciclosporina sul end point composito ditre componenti:morte,perdita del trapianto e rigetto acuto a 12,24 e 36 mesi.valutare lasicurezza complessiva del belatacept rispetto alla ciclosporina; long termextension:gli obiettivi secondari valuteranno il tasso di ar,il valore del gfr,le misure dicreatinina sierica,sopravvivenza del paziente,sopravvivenza dell`organo trapiantato,anticorpi anti`ˆ'donatore,ipertensione,iperlipidemia e ptdm.saranno,inoltre,valutati ivalori di immunogenicita` e farmacocinetica nei pazienti trattati con belatacept (ogni 6 mesie ad ogni episodio di rigetto acuto sospettato) |
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| 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 transplantwith 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 pregnancythroughout the study and for up to 8 weeks after the study in such a manner thatthe risk of pregnancy is minimized. WOCBP must have a negative serum pregnancy test (minimum sensitivity 25 IU/L orequivalent units of human chorionic gonadotropin [HCG]) within 72 hours prior to thestart 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. |
| 1.pazienti che hanno ricevuto un trapianto di rene da donatorevivente o morto con cit<24h; 2. eta` > 18 anni;3.Il paziente e` disponibile afornire il consenso informato scritto; 4.Le donne in eta` fertile devono essere disposte adutilizzare un adeguato metodo contraccettivo per 3 anni e due mesi dopo l`uscita dallostudio; Long term extension: Saranno inclusi i pazienti che: accetteranno il consensoinformato scritto relativo all`estensione dello studio a lungo termine; avranno completato i primi 3 anni dello studio IM103`ˆ'008 e resteranno nella terapia di studio (Belatacept oCiclosporina) continueranno la terapia con il farmaco MMF. |
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| 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 pairs5) Donor age < 10 years6) Subjects receiving and extended criteria donor organ as defined by:a) Donor age `‰¥ 60 yearsORb) 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/dLORc) Anticipated CIT `‰¥ 24 hoursORd) Donor with cardiac death (non-heart beating donor)7) Subjects with underlying renal disease of:a) Primary focal segmental glomerulosclerosisb) Type I or II membranoproliferative glomerulonephritis.c) Hemolytic uremic syndrome (HUS) / thrombotic thrombocytopenic purpura syndrome8) 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 C15) Subjects who are/whose allograft donor was known hepatitis B surface antigen-positive or PCR-positive for hepatitis B16) Subjects and recipients of a graft from a donor with known HIV infection17) Subjects at risk for tuberculosis (TB). Specifically, subjects who:a) Have current clinical, radiographic or laboratory evidence of active or latent TBb) 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:`ˆ' Hemoglobin < 7 g/dL`ˆ' Platelets < 80,000/mm3`ˆ' White blood cell (WBC) count < 3000/mm3 (3 x 109/L)Chemistry:`ˆ' Bilirubin >1.5 x upper limit of normal range (ULN); Subjects who have Gilbert s syndrome and have a normal direct bilirubin are permitted`ˆ' Aspartate aminotransferase (AST) `‰¥ 2 x ULN`ˆ' Alanine aminotransferase (ALT) `‰¥ 2 x ULN24) 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. |
| 1.Donne fertili che non sono disposte o non possono utilizzare un adeguato metodocontraccettivo per evitare la gravidanza durante tutto il periodo dello studio e nelle 8 settimane successive all`ultima infusione. 2.Donne in gravidanza o in allattamento. 3.Donnecon un test di gravidanza positivo all`arruolamento o prima della somministrazione delfarmaco in studio. 4.Il donatore e/o il rene donato rispettano almeno uno (a,b,c,d) .deiseguenti criteri estesi per la donazione dell`organo: eta` del donatore e 60 anni; oppure eta`del donatore tra 50`ˆ'59 anni anni con almeno due dei seguenti tre criteri: 1) eventocerebrovascolare come causa di morte (CVA) + ipertensione + creatinina sierica > 1,5mg/dL; 2) ipertensione + creatinina sierica > 1,5 mg/dL; 3) creatinina sierica > 1,5 mg/dL;oppure+ CVA tempo di ischemia fredda e 24 ore donatore deceduto di morte cardiaca(donatore non a cuore pulsante) 4.Eta` del donatore < 10 anni. 5.Pazienti con una patologiarenale di base quale: a)Glomerulosclerosi focale segmentale (comprovata da biopsia)b)Glomerulonefrite memabranoproliferativa di tipo I e di tipo II c)Sindrome emoliticauremica/sindrome di porpora trombotica trombocitopenica 6.Pazienti che effettuano il primotrapianto con un valore attuale di Panel Reactive Antibody (PRA) e 50%, o pazientiritrapiantati con un Panel Reactive Antibody (PRA) e 30%. 7.Pazienti con precedente perdita dell`organo per rigetto acuto 8.Pazienti con un precedente trapianto di organo solido9.Pazienti riceventi un trapianto concomitante di un organo solido (cuore, fegato, pancreas)o di cellule (isole, midollo, o cellule staminali). 10.Pazienti riceventi un doppio rene11.Pazienti con anticorpi positivi per l`Epatite C o PCR positivi all`Epatite C. 12.Pazientipositivi all`antigene di superficie dell`Epatite B o PCR positivi all`Epatite B. 13.Pazienti con un infezione HIV conosciuta. 14.Pazienti con tubercolosi attiva (TB) che ha richiesto untrattamento nei tre mesi precedenti o pazienti che sono stati sottoposti ad una combinazionedi tre o piu terapie per la TB. 15.Pazienti con una qualsiasi infezione attiva o che abbianocontroindicazioni che normalmente escluderebbero l`effettuazione del trapianto. 16.Pazienticon un storia medica di cancro ( ad eccezione di tumori delle cellule della pelle non melanoma, curato tramite resezione) negli ultimi 5 anni. 17.Pazienti con una storia di abusodi sostanze (farmaci e alcool). 18.Pazienti con uno dei seguenti valori di laboratorio sono esclusi: emoglobina al di sotto di 7 g/dL piastrine al di sotto delle 80.000/mm3 leucocititotali (WBC) al di sotto di 3000/ mm3 AST, ALT piu` di 2 volte il limite piu alto dinormalita` bilirubina piu di una volta e mezzo sopra il valore piu alto di normalita`.19.Pazienti che presentano un difficile accesso endovenoso. 20.Pazienti con una storia diallergia vera agli agenti di contrasto iodinati somministrati per via endovenosa utilizzati neiraggi X. 21.Pazienti che stanno ricevendo un agente immunosoppressivo per altre indicazioni(ad esempio metotrexate, infliximab, etanercept) o pazienti per i quali e` probabile luso diquesti agenti nei tre anni di studio. 22.Pazienti precedentemente trattati con Belatacept.+Partecipazione alla Long term extension vedere protocollo Appendix 5 sec 5.2 |
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| 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. |
| valutare l`effetto del balatacept rispetto alla ciclosporina sullasopravvivenza del soggetto e dell`organo trapiantato a 12 mesi;valutare il gfr al 12° mese; valutare l`incidenza del rigetto nei 12mesi. |
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| 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 | 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 | 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 |
| OTHER 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.8.2.4 | Number of treatment arms in the trial | 3 |
| 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 | 37 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| 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
|
| La Long term extension dello studio continuera` fino a quando il Bel. diventera` disponibile in commercio nel paese in cui sono stati arruolati i pazienti o quando BMS, decidera` di terminare lo sviluppo del farmaco in studio per questa indicazione. |
|
| 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 |
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