Clinical trial NCT02217410: CCFZ533X2201 - PoC Study in de Novo Renal Transplantation
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Kidney Transplantation
Keywords: renal, de novo,
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2014-08-15
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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).

Primary outcomes:
measure: Mean Cmax Pharmacokinetic Parameter- Part I
timeFrame: Day 1
measure: Mean Tmax Pharmacokinetic Parameter - Part I
timeFrame: Day 1
measure: Mean AUClast Pharmacokinetic Parameter - Part I
timeFrame: Day 1
measure: Efficacy as Defined by the Frequency and Severity (Banff Classification) of Treated Biopsy Proven Acute Rejection (tBPAR) Adjudicated Data - Part II
timeFrame: 3, 6, 9, and 12 months
Secondary outcomes:
measure: Total Soluble CD40 and Total Soluble CD154 Concentrations in Plasma - Part 1
timeFrame: Baseline to end of study (Day 1, Day 29, Day 337)
measure: Free CD40 and Total CD40 on B Cells - Part II
timeFrame: Baseline to end of study (Day 1/predose)
measure: Anti-CFZ533 Antibodies - Part I
timeFrame: Baseline to end of study
measure: Anti-CFZ533 Antibodies - Part II
timeFrame: Baseline to end of study (screening, baseline, Day 141, Day 225, Day 309, Study Completion)
measure: eGFR - Part II
timeFrame: Day 1, Day 29, Day 337,
measure: CFZ533 Plasma PK Concentrations - Part II
timeFrame: throughout study period (day 84 to day 336)
measure: Total sCD40 Plasma Concentrations - Part II
timeFrame: 12 months
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Novartis Investigative Site
state: Colorado
city: Baltimore
country: United States
facility: Novartis Investigative Site
state: Maryland
city: Ann Arbor
country: United States
facility: Novartis Investigative Site
state: Michigan
city: Detroit
country: United States
facility: Novartis Investigative Site
state: Michigan
city: Livingston
country: United States
facility: Novartis Investigative Site
state: New Jersey
city: Cincinnati
country: United States
facility: Novartis Investigative Site
state: Ohio
city: São Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
city: Utrecht
country: Netherlands
facility: Novartis Investigative Site
state: The Netherlands
city: Groningen
country: Netherlands
facility: Novartis Investigative Site
city: Rotterdam
country: Netherlands
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: