Study of Efficacy, Safety, Tolerability, Pharmacokinetic (PK) and Pharmacodynamic (PD) of an Anti-CD40 Monoclonal Antibody, CFZ533, in Liver Transplant Recipients With Additional 12-month Follow-up and Long-term Extension

NCT03781414 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: CCFZ533A22022018-001836-24
• Study Type: interventional
• Target: 129
• Locations: 10 countries
• Sites: 29

Brief Summary

This was a multicenter, open-label, active-controlled study to evaluate the efficacy, safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of two CFZ533 maintenance doses in de novo liver transplant recipients.

Conditions

Liver Transplant Rejection

Keywords

Liver transplantation; de novo recipients; deceased donor; CFZ533; CNI-free immunosuppression; Transplant rejection

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients With Composite Event (Biopsy Proven Acute Rejection (BPAR), Graft Loss or Death) Over 12 Months

  The occurrence of biopsy proven acute rejection (BPAR) was evaluated based on central pathologist evaluation. Graft loss and death was evaluated as per local evaluation.

  Baseline to Month 12

Secondary Outcomes (3)

• Mean Change in Estimated Glomerular Filtration Rate (eGFR) From Randomization to Month 12

  Baseline to Month 12

• Number of Participants With Treatment Emergent Adverse Events

  Baseline up to 14 weeks after last dose of study medication (CFZ533 participants) and until 12 weeks for TAC participants, up to approx. 184 weeks.

• Percentage of Patients With Dose Interruptions and Permanent Discontinuation of Study Treatment

  Baseline to Month 24

Study Arms (3)

TAC Control

ACTIVE COMPARATOR

Tacrolimus (TAC) + Mycophenolate mofetil (MMF) + Corticosteroids (CS) up to End of Study (EOS). Initial TAC target trough were between 5-15 ng/mL during the run-in period. From randomization onwards, the TAC levels were adjusted as per local label.

Drug: Tacrolimus - MMF - corticosteroids

CFZ533 600 mg regimen

EXPERIMENTAL

Loading doses of 30 mg/kg IV on Day 8 (with +/- 2 days window), and 15 mg/kg IV on Day 15. The subcutaneous (SC) administration of 600 mg (2 injections of 2 mL CFZ533 at 150 mg/mL) every 2 weeks started on Day 29, in combination with MMF and CS up to EOS.

Biological: CFZ533

CFZ533 300 mg regimen

EXPERIMENTAL

Single loading dose of 30 mg/kg IV on Day 8 (with +/- 2 days window). The SC administration of 300 mg (1 injection of 2 mL CFZ533 at 150 mg/mL) every 2 weeks started on Day 29, in combination with MMF and CS up to EOS.

Biological: CFZ533

Interventions

CFZ533 BIOLOGICAL

Comparison with standard of care immunosuppression

CFZ533 300 mg regimen; CFZ533 600 mg regimen

Tacrolimus - MMF - corticosteroids DRUG

Standard of care immunosuppresive regimen

TAC Control

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Screening period up to liver transplantation:
• Written informed consent obtained before any assessment.
• Male or female patients between 18 to 70 years of age.
• Recipients of a primary liver transplant from a deceased donor.
• Up to date vaccination as per local immunization schedules.
• Recipients tested negative for HIV.
• MELD score ≤ 30.
• Transplantation to occur within defined screening period following informed consent signature.
• At randomization (Day 8 +/- 2):
• Recipients with no active HCV and HBV replication.
• Allograft is functioning at an acceptable level by the time of randomization as defined by AST, ALT and Alkaline Phosphatase levels ≤ 5 times ULN and Total Bilirubin ≤ 2 times ULN.
• Renal function (eGFR, MDRD-4 formula) ≥ 30 mL/min/1.73 m2 based on most recent post-transplant value prior to randomization.
• Recipients who have been initiated on an immunosuppressive regimen that contains TAC, mycophenolate mofetil (MMF) and corticosteroids (CS) as per protocol.

You may not qualify if:

• Screening period up to liver transplantation:
• Use of other investigational drugs at screening within 30 days or 5 half-lives of screening.
• Recipients of multiple solid organ or islet cell transplants, or recipients that have previously received a tissue transplant, or a combined liver-kidney transplant.
• Recipients of a liver from a donor after cardiac death (DCD), from a living donor, or of a split liver.
• Recipient who tested negative for Epstein Barr virus (EBV) within 28 days prior to baseline visit.
• Recipients receiving an ABO incompatible allograft.
• History of malignancy of any organ system (except hepatocellular carcinoma (HCC) or localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there was evidence of local recurrence or metastases.
• Hepatocellular carcinoma that did not fulfill Milan criteria (1 nodule ≤ 5 cm, 2-3 nodules all ≤ 3 cm, without evidence of metastatic disease or vascular invasion) at the time of transplantation.
• Recipients transplanted for acute liver failure (does not apply to acute on chronic liver failure).
• Any use of antibody induction therapy, or use of any immunosuppressive medications (or other medications prohibited by the protocol).
• Patients who have received a live vaccine within four weeks prior to transplantation.
• Recipients with HIV positive donor.
• Recipients with donors HBsAg positive.
• Recipients who were HCV antibody-positive without documented sustained viral response (SVR) at 12 weeks after finishing anti HCV treatment (e.g., direct-acting antivirals).
• Recipients with HCV RNA-positive donors.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (29)

University of Southern California

Los Angeles, California, 90033, United States

Location

University of Colorado Hospital - Aurora

Aurora, Colorado, 80045, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202 2689, United States

Location

Wash U School of Medicine

St Louis, Missouri, 63110, United States

Location

Duke Univ Medical Center

Durham, North Carolina, 27710, United States

Location

University Of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Medical University of South Carolina MUSC

Charleston, South Carolina, 29425, United States

Location

The Methodist Hospital

Houston, Texas, 77030, United States

Location

Novartis Investigative Site

CABA, Buenos Aires, C1118AAT, Argentina

Location

Novartis Investigative Site

CABA, Buenos Aires, C1181ACH, Argentina

Location

Novartis Investigative Site

Caba, Buenos Aires, C1280AEB, Argentina

Location

Novartis Investigative Site

Ghent, 9000, Belgium

Location

Novartis Investigative Site

Prague, 146 24, Czechia

Location

Novartis Investigative Site

Chambray-lès-Tours, 37170, France

Location

Novartis Investigative Site

Lille, 59037, France

Location

Novartis Investigative Site

Montpellier, 34295, France

Location

Novartis Investigative Site

Villejuif, 94805, France

Location

Novartis Investigative Site

Regensburg, Bavaria, 93053, Germany

Location

Novartis Investigative Site

Berlin, 13353, Germany

Location

Novartis Investigative Site

Hamburg, 20246, Germany

Location

Novartis Investigative Site

Münster, 48149, Germany

Location

Novartis Investigative Site

Budapest, H-1083, Hungary

Location

Novartis Investigative Site

Pisa, PI, 56124, Italy

Location

Novartis Investigative Site

Rotterdam, South Holland, 3015 GD, Netherlands

Location

Novartis Investigative Site

Seville, Andalusia, 41013, Spain

Location

Novartis Investigative Site

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08036, Spain

Location

Novartis Investigative Site

Madrid, 28009, Spain

Location

Related Links

• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Interventions

iscalimab

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+ 1 862 778 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 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2018
• First Posted: December 19, 2018
• Study Start: October 7, 2019
• Primary Completion: April 20, 2023
• Study Completion: April 20, 2023
• Last Updated: May 16, 2025
• Results First Posted: July 3, 2024

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

ES (4); IT (1); HU (1); BE (1); AR (3); FR (4); NL (1); US (9); CZ (1); DE (4)