CCFZ533X2201 - PoC Study in de Novo Renal Transplantation

Kidney Transplantation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02217410
• Other study ID #: CCFZ533X2201
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: February 5, 2015
• Est. completion date: November 29, 2017

Study information

• Verified date: September 2021
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: November 29, 2017
• Est. primary completion date: November 29, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Kidney Transplantation

Intervention

Biological:
• CFZ533

Drug:
• Tacrolimus (Tac)

• Mycophenolate mofetil (MMF)

• Corticosteroids (CS)

Biological:
• anti-IL2 Induction

Locations

Country	Name	City	State
Brazil	Novartis Investigative Site	São Paulo	SP
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Heidelberg
Netherlands	Novartis Investigative Site	Groningen
Netherlands	Novartis Investigative Site	Rotterdam
Netherlands	Novartis Investigative Site	Utrecht	The Netherlands
United States	Novartis Investigative Site	Ann Arbor	Michigan
United States	Novartis Investigative Site	Aurora	Colorado
United States	Novartis Investigative Site	Baltimore	Maryland
United States	Novartis Investigative Site	Cincinnati	Ohio
United States	Novartis Investigative Site	Detroit	Michigan
United States	Novartis Investigative Site	Livingston	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Brazil,  Germany,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	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)
Secondary	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)
Secondary	Anti-CFZ533 Antibodies - Part I	To evaluate the immunogenicity of CFZ533 via the quantitative analysis of anti-CFZ533 antibodies	Baseline to end of study
Secondary	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)
Secondary	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,
Secondary	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)
Secondary	Total sCD40 Plasma Concentrations - Part II	To quantify the change from baseline and recovery of peripheral blood total soluble CD40	12 months

External Links

•   Plain Language Trial Summary is available on novartisclinicaltrials.com