CCFZ533X2201 - PoC Study in de Novo Renal Transplantation

Phase 1

Completed

• Conditions: Kidney Transplantation
• Interventions: Biological: CFZ533; Drug: Tacrolimus (Tac); Drug: Mycophenolate mofetil (MMF); Drug: Corticosteroids (CS); Biological: anti-IL2 Induction

• Registration Number: NCT02217410
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-08-07
• Study First Submitted QC: 2014-08-13
• Study First Posted: 2014-08-15
• Study Start: 2015-02-05
• Primary Completion: 2017-11-29
• Study Completion: 2017-11-29
• Results First Submitted: 2018-11-28
• Results First Submitted QC: 2018-11-28
• Results First Posted: 2018-12-21
• Status Verified: 2021-09
• Last Update Submitted: 2021-09-24
• Last Update Posted: 2021-09-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 59

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Regimen A	CFZ533	CFZ533 administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS).
Regimen A	Tacrolimus (Tac)	CFZ533 administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS).
Regimen A	Mycophenolate mofetil (MMF)	CFZ533 administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS).
Regimen A	Corticosteroids (CS)	CFZ533 administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS).
Regimen B	CFZ533	CFZ533 administered with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction
Regimen B	Mycophenolate mofetil (MMF)	CFZ533 administered with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction
Regimen B	Corticosteroids (CS)	CFZ533 administered with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction
Regimen B	anti-IL2 Induction	CFZ533 administered with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction
Regimen C	Tacrolimus (Tac)	Standard of care (SoC) \[concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction\]
Regimen C	Mycophenolate mofetil (MMF)	Standard of care (SoC) \[concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction\]
Regimen C	Corticosteroids (CS)	Standard of care (SoC) \[concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction\]
Regimen C	anti-IL2 Induction	Standard of care (SoC) \[concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction\]

Primary Outcome Measures

Name	Time	Method
Mean Tmax Pharmacokinetic Parameter - Part I	Day 1	Quantify pharmacokinetics of CFZ533 in combination with MMF, CS, and tacrolimus in de novo renal transplant patients during the treatment and follow-up periods.
Mean AUClast Pharmacokinetic Parameter - Part I	Day 1	Quantify pharmacokinetics of CFZ533 in combination with MMF, CS, and tacrolimus in de novo renal transplant patients during the treatment and follow-up periods.
Efficacy as Defined by the Frequency and Severity (Banff Classification) of Treated Biopsy Proven Acute Rejection (tBPAR) Adjudicated Data - Part II	3, 6, 9, and 12 months	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.
Mean Cmax Pharmacokinetic Parameter- Part I	Day 1	Pharmacokinetics as defined by the systemic concentrations and Cmax of certain immunosuppressant medications used in Part I

Secondary Outcome Measures

Name	Time	Method
CFZ533 Plasma PK Concentrations - Part II	throughout study period (day 84 to day 336)	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.
Anti-CFZ533 Antibodies - Part II	Baseline to end of study (screening, baseline, Day 141, Day 225, Day 309, Study Completion)	To evaluate the immunogenicity of CFZ533 via the quantitative analysis of anti-CFZ533 antibodies
eGFR - Part II	Day 1, Day 29, Day 337,	Renal function as assessed by MDRD (Modification of Diet in Renal Disease) formula.; eGFR: Estimated glomerular filtration rate
Total sCD40 Plasma Concentrations - Part II	12 months	To quantify the change from baseline and recovery of peripheral blood total soluble CD40
Total Soluble CD40 and Total Soluble CD154 Concentrations in Plasma - Part 1	Baseline to end of study (Day 1, Day 29, Day 337)	To quantify the change from baseline and recovery of peripheral blood total soluble CD40 and total soluble CD154
Free CD40 and Total CD40 on B Cells - Part II	Baseline to end of study (Day 1/predose)	The magnitude and duration of peripheral blood CD40 occupancy. MESF: molecules of equivalent soluble fluorochrome
Anti-CFZ533 Antibodies - Part I	Baseline to end of study	To evaluate the immunogenicity of CFZ533 via the quantitative analysis of anti-CFZ533 antibodies

Trial Locations

Locations (1)

Novartis Investigative Site; 🇳🇱 Rotterdam, Netherlands