Study of Efficacy, Safety, Tolerability, Pharmacokinetic (PK) and Pharmacodynamic (PD) of an Anti-CD40 Monoclonal Antibody, CFZ533, in Kidney Transplant Recipients

NCT03663335 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: CCFZ533A22012017-003607-22
• Study Type: interventional
• Target: 418
• Locations: 20 countries
• Sites: 74

Brief Summary

This study was to compare CFZ533 to tacrolimus (TAC) in prevention of organ rejection in kidney transplant.

Conditions

Kidney Transplantation

Keywords

Kidney Transplant Rejection; Renal transplantation; CFZ533; CNI-free immunosuppression; transplant rejection; allograft rejection

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Composite Efficacy Failure Event (Biopsy Proven Acute Rejection (BPAR), Graft Loss or Death) Over 12 Months Post-transplantation (Cohort 1)

  The composite efficacy failure event is defined as any of the following: (1) biopsy-proven acute rejection (BPAR) or (2) graft loss or (3) death. BPAR (BANFF ≥ 1A) is based on the central and adjudicated assessments. Graft loss is defined as when the allograft was presumed lost on the day the participant started dialysis and was not able to subsequently be removed from dialysis or re-transplanted. If the participant underwent allograft nephrectomy prior to start of permanent dialysis, the day of the nephrectomy was day of graft loss.

  12 Months

• Percentage of Participants With Composite Efficacy Failure Event (BPAR, Graft Loss or Death) Over 12 Months Post-conversion (Cohort 2)

  The composite efficacy failure event is defined as any of the following: (1) biopsy-proven acute rejection (BPAR) or (2) graft loss or (3) death. BPAR (BANFF ≥ 1A) is based on the central and adjudicated assessments. Graft loss is defined as when the allograft was presumed lost on the day the participant started dialysis and was not able to subsequently be removed from dialysis or re-transplanted. If the participant underwent allograft nephrectomy prior to start of permanent dialysis, the day of the nephrectomy was day of graft loss.

  12 Months

Secondary Outcomes (6)

• Cohort 1: Mean Estimated Glomerular Filtration Rate (eGFR) ((MDRD4) at 12 Months Post-transplantation

  12 months

• Cohort 2: Mean Change in Estimated Glomerular Filtration Rate (eGFR) ((MDRD4) at 12 Months Post-conversion

  12 months

• Free CFZ533 Plasma Concentrations Over Time (Cohort 1)

  Day 1-Pre-Dose to Month 30-Pre-Dose

• Free CFZ533 Plasma Concentrations Over Time (Cohort 2)

  Day 1-Pre-Dose to Month 30-Pre-Dose

• Semi-quantiative Analysis of Anti-CFZ533 Antibodes in Plasma (CFZ533 Treated Patients Only) (Cohort 1)

  24 Months

Study Arms (5)

Arm 1/Cohort 1: CFZ533 600 mg + Mycophenolate Mofetil (MMF) + Corticosteroids

EXPERIMENTAL

Eligible patients were randomized to CFZ533 600 mg sc bi-weekly (Q2W) + Mycophenolate Mofetil (MMF) + Corticosteroids. Patients randomized to CFZ533 arms were administered the first dose of CFZ533 at 30 mg/kg IV pre- or intra-operatively (Day 1) with completion of the infusion within one hour of unclamping and prior graft revascularization, in combination with MMF and corticosteroids. MMF and corticosteroids might be initiated prior to surgery according to local practice. A second IV dose of CFZ533 at 15 mg/kg was infused at Day 5 post-transplant. Subsequent doses starting at Day 15: 600 mg sc (2 injections of 2 mL CFZ533 at 150 mg/mL) Q2W, up to a planned Month 59.5 visit.

Biological: CFZ533 - Cohort 1/Cohort 2; Drug: Mycophenolate Mofetil (MMF); Drug: Corticosteroids (CS); Drug: Induction therapy: basiliximab; Drug: Induction therapy: rabbit anti-thymocyte globulin (rATG)

Arm 2/Cohort 1: CFZ533 300 mg + Mycophenolate Mofetil (MMF) + Corticosteroids

EXPERIMENTAL

Eligible patients were randomized to CFZ533 300 mg sc bi-weekly (Q2W) + Mycophenolate Mofetil (MMF) + Corticosteroids. Patients randomized to CFZ533 arms were administered the first dose of CFZ533 at 30 mg/kg IV pre- or intra-operatively (Day 1) with completion of the infusion within one hour of unclamping and prior graft revascularization, in combination with MMF and corticosteroids. MMF and corticosteroids might be initiated prior to surgery according to local practice. A second IV dose of CFZ533 at 15 mg/kg was infused at Day 5 post-transplant. Subsequent doses starting at Day 15: 300 mg sc (1 injection of 2 mL CFZ533 at 150 mg/mL, and 1 injection of 2 mL of the generic placebo) sc, Q2W, up to a planned Month 59.5 visit.

Biological: CFZ533 - Cohort 1/Cohort 2; Drug: Mycophenolate Mofetil (MMF); Drug: Corticosteroids (CS); Drug: Induction therapy: basiliximab; Drug: Induction therapy: rabbit anti-thymocyte globulin (rATG); Drug: Placebo 1 mL

Arm 3/Cohort 1: Control/Standard of Care: Tacrolimus (TAC) + MMF + Corticosteroids

ACTIVE COMPARATOR

Patients randomized to the TAC control arm were initiated on a TAC-based regimen with MMF and corticosteroids.

Drug: Mycophenolate Mofetil (MMF); Drug: Corticosteroids (CS); Drug: Tacrolimus; Drug: Induction therapy: basiliximab; Drug: Induction therapy: rabbit anti-thymocyte globulin (rATG)

Arm 1/Cohort 2: CFZ533 450 mg + MMF ± Corticosteroids

EXPERIMENTAL

Eligible patients who were 6 to 24 months post renal transplantation and were on a stable regimen containing TAC+MMF/Enteric-coated mycophenolate sodium (EC-MPS)±CS were randomized to CFZ533 450 mg sc Q2W. On Day 1, patients randomized to Arm 1 were administered the 1st dose of CFZ533 at 30 mg/kg IV, concomitantly with MMF/EC-MPS and 50% of the current TAC dose. At Day 15, CFZ533 were administered sc at 450 mg (1 injection of 2 mL \& 1 injection of 1 mL CFZ533 at 150 mg/mL) concomitantly with MMF/EC-MPS, and TAC reduced by a further 50%. By Day 29, patients were fully tapered off their TAC. Subsequent doses of 450 mg sc Q2W, were administered in combination with MMF/EC-MPS with or without corticosteroids, up to Month 59.5 visit.

Biological: CFZ533 - Cohort 1/Cohort 2; Drug: Corticosteroids (CS); Drug: Maintenance population: EC-MPS; Drug: Maintenance population: MMF

Arm 2/Cohort 2: TAC + MMF ± Corticosteroids

ACTIVE COMPARATOR

Patients received TAC-based regimen throughout the study.

Drug: Corticosteroids (CS); Drug: Tacrolimus; Drug: Maintenance population: EC-MPS; Drug: Maintenance population: MMF

Interventions

CFZ533 - Cohort 1/Cohort 2 BIOLOGICAL

CFZ533 was administered either by intravenous infusion or subcutaneous injection

Arm 1/Cohort 1: CFZ533 600 mg + Mycophenolate Mofetil (MMF) + Corticosteroids; Arm 1/Cohort 2: CFZ533 450 mg + MMF ± Corticosteroids; Arm 2/Cohort 1: CFZ533 300 mg + Mycophenolate Mofetil (MMF) + Corticosteroids

Mycophenolate Mofetil (MMF) DRUG

Per local practice, 250 mg or 500 mg taken orally or 500 mg taken intravenously.

Arm 1/Cohort 1: CFZ533 600 mg + Mycophenolate Mofetil (MMF) + Corticosteroids; Arm 2/Cohort 1: CFZ533 300 mg + Mycophenolate Mofetil (MMF) + Corticosteroids; Arm 3/Cohort 1: Control/Standard of Care: Tacrolimus (TAC) + MMF + Corticosteroids

Corticosteroids (CS) DRUG

Taken either orally or intravenously.

Arm 1/Cohort 1: CFZ533 600 mg + Mycophenolate Mofetil (MMF) + Corticosteroids; Arm 1/Cohort 2: CFZ533 450 mg + MMF ± Corticosteroids; Arm 2/Cohort 1: CFZ533 300 mg + Mycophenolate Mofetil (MMF) + Corticosteroids; Arm 2/Cohort 2: TAC + MMF ± Corticosteroids; Arm 3/Cohort 1: Control/Standard of Care: Tacrolimus (TAC) + MMF + Corticosteroids

Tacrolimus DRUG

Standard of care immunosuppressive regimen

Arm 2/Cohort 2: TAC + MMF ± Corticosteroids; Arm 3/Cohort 1: Control/Standard of Care: Tacrolimus (TAC) + MMF + Corticosteroids

Induction therapy: basiliximab DRUG

Lyophilized solution taken intravenously

Arm 1/Cohort 1: CFZ533 600 mg + Mycophenolate Mofetil (MMF) + Corticosteroids; Arm 2/Cohort 1: CFZ533 300 mg + Mycophenolate Mofetil (MMF) + Corticosteroids; Arm 3/Cohort 1: Control/Standard of Care: Tacrolimus (TAC) + MMF + Corticosteroids

Induction therapy: rabbit anti-thymocyte globulin (rATG) DRUG

Lyophilized vial taken intravenously.

Also known as: Lyophilized solution

Arm 1/Cohort 1: CFZ533 600 mg + Mycophenolate Mofetil (MMF) + Corticosteroids; Arm 2/Cohort 1: CFZ533 300 mg + Mycophenolate Mofetil (MMF) + Corticosteroids; Arm 3/Cohort 1: Control/Standard of Care: Tacrolimus (TAC) + MMF + Corticosteroids

Maintenance population: EC-MPS DRUG

Tablet that is taken orally

Arm 1/Cohort 2: CFZ533 450 mg + MMF ± Corticosteroids; Arm 2/Cohort 2: TAC + MMF ± Corticosteroids

Maintenance population: MMF DRUG

Tablet that is taken orally

Arm 1/Cohort 2: CFZ533 450 mg + MMF ± Corticosteroids; Arm 2/Cohort 2: TAC + MMF ± Corticosteroids

Placebo 1 mL DRUG

Solution taken subcutaneously and was used for blinding of the CFZ533 doses.

Arm 2/Cohort 1: CFZ533 300 mg + Mycophenolate Mofetil (MMF) + Corticosteroids

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 obtained before any assessment.
• Male or female patient ≥ 18 years old.
• Up to date vaccination as per local immunization schedules.
• Recipients of a primary kidney transplant from a brain-dead donor, living unrelated or non-human leukocyte antigen (HLA) identical living related donors.
• Recipients of a kidney with a cold ischemia time \< 24 hours.
• Recipients of a primary graft received 6 to 24 months prior enrollment, on a regimen containing TAC+MMF/ Enteric-coated mycophenolate sodium (EC-MPS)±corticosteroids (CS).
• Patients with an actual eGFR according to Modification of Diet in Renal Disease (MDRD-4) ≥ 45 mL/min/1.73m2.

You may not qualify if:

• Recipient who tests positive for anti-HIV, HBsAg or anti-HCV (without proof of sustained viral response (SVR12) after anti-HCV treatment) within 28 days prior to baseline visit.
• Recipient who tests negative for Epstein Barr virus (EBV) within 28 days prior to baseline visit.
• Evidence of advanced liver disease (Child-Pugh C), or any sign of liver decompensation.
• Patient with severe systemic infections, current or within the two weeks prior to randomization.
• History of malignancy of any organ system, treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases, with the exception of localized excised non-melanomatous skin lesions.
• Patients who weighed less than 30 kg or more than 180 kg.
• Multi-organ transplant recipients, including en bloc and dual kidney transplantation, or prior kidney transplant
• Recipients of an organ from a donor after cardiac death.
• Recipient of an organ from an HLA identical living related donor.
• Recipients of kidneys from donors who were older than \>65 years.
• Recipients of kidneys from donors with terminal serum creatinine \> 2 mg/dL.
• Patients at high immunological risk for rejection as determined for assessment of anti-donor reactivity:
• high panel reactive antibodies\> 20% or
• Presence of pre-formed DSA. Results 12 weeks prior to enrollment were acceptable if no blood transfusion or abortion occurred during this period.
• Recipient of a kidney from a donor who tests positive for HIV, HBsAg or HCV.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (74)

Novartis Investigative Site

Los Angeles, California, 90033, United States

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Novartis Investigative Site

San Francisco, California, 94143 0116, United States

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Novartis Investigative Site

Aurora, Colorado, 80045, United States

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Novartis Investigative Site

Chicago, Illinois, 60611, United States

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Novartis Investigative Site

Chicago, Illinois, 60612, United States

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Novartis Investigative Site

Kansas City, Kansas, 66103, United States

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Novartis Investigative Site

Baltimore, Maryland, 21201, United States

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Novartis Investigative Site

Boston, Massachusetts, 02114, United States

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Novartis Investigative Site

Detroit, Michigan, 48202 2689, United States

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Novartis Investigative Site

St Louis, Missouri, 63110, United States

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Novartis Investigative Site

Durham, North Carolina, 27710, United States

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Novartis Investigative Site

Cincinnati, Ohio, 45219, United States

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Novartis Investigative Site

Cincinnati, Ohio, 45267-0585, United States

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Novartis Investigative Site

Dallas, Texas, 75390, United States

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Novartis Investigative Site

Seattle, Washington, 98195, United States

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Novartis Investigative Site

Buenos Aires, W3400ABH, Argentina

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Novartis Investigative Site

Corrientes, W3400, Argentina

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Novartis Investigative Site

Córdoba, X5016KEH, Argentina

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Novartis Investigative Site

Camperdown, New South Wales, 2050, Australia

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Novartis Investigative Site

Adelaide, South Australia, 5000, Australia

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Novartis Investigative Site

Clayton, Victoria, 3168, Australia

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Novartis Investigative Site

Leuven, 3000, Belgium

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Novartis Investigative Site

Porto Alegre, Rio Grande do Sul, 90020-090, Brazil

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Novartis Investigative Site

São Paulo, São Paulo, 04038-002, Brazil

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Novartis Investigative Site

São Paulo, São Paulo, 05403 000, Brazil

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Novartis Investigative Site

Vancouver, British Columbia, V6Z 1Y6, Canada

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Novartis Investigative Site

Prague, 146 24, Czechia

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Novartis Investigative Site

Bordeaux, 33076, France

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Novartis Investigative Site

Créteil, 94010, France

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Novartis Investigative Site

Grenoble, 38043, France

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Novartis Investigative Site

Lyon, 69003, France

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Novartis Investigative Site

Nantes, 44093, France

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Novartis Investigative Site

Paris, 75015, France

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Novartis Investigative Site

Toulouse, 31054, France

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Novartis Investigative Site

Tours, 37044, France

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Novartis Investigative Site

Regensburg, Bavaria, 93053, Germany

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Novartis Investigative Site

Berlin, 13353, Germany

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Novartis Investigative Site

Dresden, 01307, Germany

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Novartis Investigative Site

Erlangen, 91054, Germany

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Novartis Investigative Site

Essen, 45147, Germany

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Novartis Investigative Site

Hamburg, 20246, Germany

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Novartis Investigative Site

Heidelberg, 69120, Germany

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Novartis Investigative Site

Mainz, 55131, Germany

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Novartis Investigative Site

Budapest, H-1083, Hungary

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Novartis Investigative Site

Debrecen, 4032, Hungary

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Novartis Investigative Site

Milan, MI, 20132, Italy

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Novartis Investigative Site

Roma, RM, 00133, Italy

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Novartis Investigative Site

Nagakute, Aichi-ken, 480-1195, Japan

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Novartis Investigative Site

Nagoya, Aichi-ken, 466-8650, Japan

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Novartis Investigative Site

Sapporo, Hokkaido, 060 8648, Japan

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Novartis Investigative Site

Sapporo, Hokkaido, 060-8604, Japan

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Novartis Investigative Site

Yokohama, Kanagawa, 232 0024, Japan

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Novartis Investigative Site

Tomigusuku, Okinawa, 9010224, Japan

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Novartis Investigative Site

Suita, Osaka, 565 0871, Japan

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Novartis Investigative Site

Kumamoto, 861-8520, Japan

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Novartis Investigative Site

Osaka, 545-8586, Japan

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Novartis Investigative Site

Riga, LV 1002, Latvia

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Novartis Investigative Site

Rotterdam, South Holland, 3015 GD, Netherlands

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Novartis Investigative Site

Groningen, 9713 GZ, Netherlands

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Novartis Investigative Site

Utrecht, 3584CX, Netherlands

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Novartis Investigative Site

Oslo, 0424, Norway

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Novartis Investigative Site

Seoul, 03080, South Korea

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Novartis Investigative Site

Palma de Mallorca, Balearic Islands, 07120, Spain

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Novartis Investigative Site

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

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Novartis Investigative Site

Barcelona, Catalonia, 08003, Spain

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Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

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Novartis Investigative Site

Barcelona, Catalonia, 08036, Spain

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Novartis Investigative Site

Zaragoza, 50009, Spain

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Novartis Investigative Site

Gothenburg, 413 45, Sweden

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Novartis Investigative Site

Uppsala, 751 85, Sweden

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Novartis Investigative Site

Bern, 3010, Switzerland

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Novartis Investigative Site

Glasgow, G51 4TF, United Kingdom

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Novartis Investigative Site

London, SW17 0QT, United Kingdom

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Novartis Investigative Site

Manchester, M13 9WL, United Kingdom

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MeSH Terms

Interventions

Mycophenolic Acid; Adrenal Cortex Hormones; Tacrolimus

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Macrolides; Lactones

Limitations and Caveats

One patient in Cohort 1 randomized to the TAC arm died one day after transplantation and did not take study drug.

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 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2018
• First Posted: September 10, 2018
• Study Start: November 28, 2018
• Primary Completion: October 29, 2021
• Study Completion: October 29, 2021
• Last Updated: March 23, 2026
• Results First Posted: March 23, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

CZ (1); NO (1); SE (2); JP (9); AR (3); IT (2); AU (3); BE (1); DE (8); GB (3); ES (6); NL (3); CA (1); LA (1); KR (1); FR (8); US (15); BR (3); HU (2); CH (1)