CCFZ533X2201 - PoC Study in de Novo Renal Transplantation

Study Overview
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Brief Summary
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The purpose of this study was to investigate the safety, tolerability, pharmacokinetics (PK) and potential for CFZ533 to replace calcineurin inhibitors (CNI), while providing a similar rate of acute rejection prophylaxis and renal function in a de novo renal transplant population receiving an allograft from standard criteria donors.

Official Title
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A 12-month Randomized, Multiple Dose, Open-label, Study Evaluating Safety, Tolerability, Pharmacokinetics/Pharmacodynamics (PK/PD) and Efficacy of an Anti-CD40 Monoclonal Antibody, CFZ533, in Combination With Mycophenolate Mofetil (MMF) and Corticosteroids (CS), With and Without Tacrolimus (Tac), in de Novo Renal Transplant Recipients

Conditions
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Kidney Transplantation

Intervention / Treatment
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* Biological: CFZ533
* Drug: Tacrolimus (Tac)
* Drug: Mycophenolate mofetil (MMF)
* Drug: Corticosteroids (CS)
* Biological: anti-IL2 Induction


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Written informed consent must be obtained before any assessment is performed. Recipients of a kidney transplant from a heart-beating deceased, living unrelated or non-human leukocyte antigen (HLA) identical living related donor. Recipients of a kidney with a cold ischemia time (CIT) < 30 hours. Main Exclusion Criteria: Recipients of an organ from a non-heart beating donor. ABO incompatible or complement-dependent lymphocytotoxic (CDC) crossmatch positive transplant. Subjects receiving a second kidney allograft, unless the first allograft was lost due to surgical complication. Subjects at high immunological risk for rejection Subjects at risk for tuberculosis (TB) Subject with severe systemic infections, current or within the two weeks prior to randomization/enrollment. Any additional contraindication to the use of tacrolimus or mycophenolate mofetil according to the national labeling information of these products (see local product label).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Regimen A<br>CFZ533 administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS). | Biological: CFZ533<br> <br> Drug: Tacrolimus (Tac)<br> <br> Drug: Mycophenolate mofetil (MMF)<br> <br> Drug: Corticosteroids (CS)<br> <br> |
| Experimental: Regimen B<br>CFZ533 administered with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction | Biological: CFZ533<br> <br> Drug: Mycophenolate mofetil (MMF)<br> <br> Drug: Corticosteroids (CS)<br> <br> Biological: anti-IL2 Induction<br> <br> |
| Active Comparator: Regimen C<br>Standard of care (SoC) [concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction] | Drug: Tacrolimus (Tac)<br> <br> Drug: Mycophenolate mofetil (MMF)<br> <br> Drug: Corticosteroids (CS)<br> <br> Biological: anti-IL2 Induction<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Cmax Pharmacokinetic Parameter- Part I | Pharmacokinetics as defined by the systemic concentrations and Cmax of certain immunosuppressant medications used in Part I | Day 1 | 
| Mean Tmax Pharmacokinetic Parameter - Part I | Quantify pharmacokinetics of CFZ533 in combination with MMF, CS, and tacrolimus in de novo renal transplant patients during the treatment and follow-up periods. | Day 1 | 
| Mean AUClast Pharmacokinetic Parameter - Part I | Quantify pharmacokinetics of CFZ533 in combination with MMF, CS, and tacrolimus in de novo renal transplant patients during the treatment and follow-up periods. | Day 1 | 
| Efficacy as Defined by the Frequency and Severity (Banff Classification) of Treated Biopsy Proven Acute Rejection (tBPAR) Adjudicated Data - Part II | To assess the activity of the investigational arm as compared to the standard of care control arm in de novo renal transplant patients as measured by the frequency and severity of tBPAR as measured on the Banff classification scale. An adjudication was performed on all on cause renal biopsies by an independent expert committee blinded to therapy. | 3, 6, 9, and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Soluble CD40 and Total Soluble CD154 Concentrations in Plasma - Part 1 | To quantify the change from baseline and recovery of peripheral blood total soluble CD40 and total soluble CD154 | Baseline to end of study (Day 1, Day 29, Day 337) | 
| Free CD40 and Total CD40 on B Cells - Part II | The magnitude and duration of peripheral blood CD40 occupancy. MESF: molecules of equivalent soluble fluorochrome | Baseline to end of study (Day 1/predose) | 
| Anti-CFZ533 Antibodies - Part I | To evaluate the immunogenicity of CFZ533 via the quantitative analysis of anti-CFZ533 antibodies | Baseline to end of study | 
| Anti-CFZ533 Antibodies - Part II | To evaluate the immunogenicity of CFZ533 via the quantitative analysis of anti-CFZ533 antibodies | Baseline to end of study (screening, baseline, Day 141, Day 225, Day 309, Study Completion) | 
| eGFR - Part II | Renal function as assessed by MDRD (Modification of Diet in Renal Disease) formula. eGFR: Estimated glomerular filtration rate | Day 1, Day 29, Day 337, | 
| CFZ533 Plasma PK Concentrations - Part II | Quantify the systemic concentrations of CFZ533 in combination with MMF, CS, and tacrolimus in de novo renal transplant patients during the treatment and follow-up periods. A full pharmacokinetic analysis can be performed on the concentration-time data to evaluate the impact of renal transplantation on the various medications used in the treatment regimen. | throughout study period (day 84 to day 336) | 
| Total sCD40 Plasma Concentrations - Part II | To quantify the change from baseline and recovery of peripheral blood total soluble CD40 | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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renal, de novo,