CCFZ533X2201 - PoC Study in de Novo Renal Transplantation

NCT02217410 | Completed Phase 1 Results DMC

• 1 other identifier: CCFZ533X2201
• Study Type: interventional
• Target: 59
• Locations: 4 countries
• Sites: 14

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.

Conditions

Kidney Transplantation

Keywords

renal, de novo,

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (7)

• Total Soluble CD40 and Total Soluble CD154 Concentrations in Plasma - Part 1

  Baseline to end of study (Day 1, Day 29, Day 337)

• Free CD40 and Total CD40 on B Cells - Part II

  Baseline to end of study (Day 1/predose)

• Anti-CFZ533 Antibodies - Part I

  Baseline to end of study

• Anti-CFZ533 Antibodies - Part II

  Baseline to end of study (screening, baseline, Day 141, Day 225, Day 309, Study Completion)

• eGFR - Part II

  Day 1, Day 29, Day 337,

Study Arms (3)

Regimen A

EXPERIMENTAL

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; Drug: Tacrolimus (Tac); Drug: Mycophenolate mofetil (MMF); Drug: Corticosteroids (CS)

Regimen B

EXPERIMENTAL

CFZ533 administered with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction

Biological: CFZ533; Drug: Mycophenolate mofetil (MMF); Drug: Corticosteroids (CS); Biological: anti-IL2 Induction

Regimen C

ACTIVE COMPARATOR

Standard of care (SoC) \[concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction\]

Drug: Tacrolimus (Tac); Drug: Mycophenolate mofetil (MMF); Drug: Corticosteroids (CS); Biological: anti-IL2 Induction

Interventions

CFZ533 BIOLOGICAL

Regimen A; Regimen B

Tacrolimus (Tac) DRUG

Regimen A; Regimen C

Mycophenolate mofetil (MMF) DRUG

Regimen A; Regimen B; Regimen C

Corticosteroids (CS) DRUG

Regimen A; Regimen B; Regimen C

anti-IL2 Induction BIOLOGICAL

Regimen B; Regimen C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (14)

Novartis Investigative Site

Aurora, Colorado, 80045, United States

Location

Novartis Investigative Site

Baltimore, Maryland, 21201, United States

Location

Novartis Investigative Site

Ann Arbor, Michigan, 48109 5271, United States

Location

Novartis Investigative Site

Detroit, Michigan, 48202, United States

Location

Novartis Investigative Site

Livingston, New Jersey, 07039, United States

Location

Novartis Investigative Site

Cincinnati, Ohio, 45267-0585, United States

Location

Novartis Investigative Site

São Paulo, São Paulo, 04038-002, Brazil

Location

Novartis Investigative Site

Berlin, D-13353, Germany

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Hamburg, 20246, Germany

Location

Novartis Investigative Site

Heidelberg, 69120, Germany

Location

Novartis Investigative Site

Utrecht, The Netherlands, 3508 GA, Netherlands

Location

Novartis Investigative Site

Groningen, 9713 GZ, Netherlands

Location

Novartis Investigative Site

Rotterdam, 3000 CA, Netherlands

Location

Related Links

• Plain Language Trial Summary is available on novartisclinicaltrials.com

MeSH Terms

Interventions

iscalimab; Tacrolimus; Triamcinolone; Mycophenolic Acid; Adrenal Cortex Hormones

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2014
• First Posted: August 15, 2014
• Study Start: February 5, 2015
• Primary Completion: November 29, 2017
• Study Completion: November 29, 2017
• Last Updated: September 28, 2021
• Results First Posted: December 21, 2018

Record last verified: 2021-09

Locations

DE (4); BR (1); US (6); NL (3)