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CompletedNCT03663335CIRRUS IUpdated Mar 23, 2026Results posted

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

A Phase 2 interventional study of CFZ533 - Cohort 1/Cohort 2 and Mycophenolate Mofetil (MMF) in Kidney Transplantation, sponsored by Novartis Pharmaceuticals. Completed at 74 sites in 20 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-03-23.

Sponsored by Novartis Pharmaceuticals · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
418
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

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

Read the detailed description

The purpose of this study was to investigate the safety, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) of three CFZ533 dose regimens in kidney transplant recipients.

Study CCFZ533A2201 was a randomized, planned 60-month (5 year) study comprising of 12-months treatment for the primary analysis plus an additional 48-month treatment period. The study had 2 different cohorts: adult de novo kidney transplant recipients and maintenance kidney transplant population (6-24 months post-transplant).

The study was terminated after the interim analysis.

02

Conditions studied

  • Kidney Transplantation

Keywords

  • Kidney Transplant Rejection
  • Renal transplantation
  • CFZ533
  • CNI-free immunosuppression
  • transplant rejection
  • allograft rejection
03

In context

Lead sponsor

Novartis Pharmaceuticals is the lead sponsor of 2,673 studies on the registry; 228 are open to participants now.

Of its 576 completed or terminated interventional studies of FDA-regulated products, 431 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

Key inclusion criteria for both cohorts

  • Written informed consent obtained before any assessment.
  • Male or female patient ≥ 18 years old.
  • Up to date vaccination as per local immunization schedules.

Key inclusion criteria specific to Cohort 1:

  • 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.

Key inclusion criteria specific to Cohort 2:

  • 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.

Exclusion criteria

Exclusion Criteria:

Key exclusion criteria for both cohorts

  • 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.

Key exclusion criteria specific to Cohort 1:

  • 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.
  • ABO incompatible or complement-dependent lymphocytotoxic crossmatch positive transplant (isolated positive B cell crossmatches were not an exclusion criterion).
  • 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.

Key exclusion criteria to Cohort 2

  • Recipients of a kidney re-transplant.
  • Recipient of a multi-organ transplant, including en bloc and dual kidney transplantation.
  • DSA within 12 weeks prior enrollment.
  • eGFR decline ≥10.0 mL/min within 12 weeks prior enrollment.
  • Ongoing rejection or rejection that required treatment within 12 weeks prior enrollment.
  • Severe humoral and/or cellular rejection (BANFF ≥ IIb) within 12 weeks before enrollment.
  • Proteinuria > 1 g/day or UPCR >1.2 mg/mg at time of enrollment
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
418 participants (actual)

Study arms

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

    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)

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

    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

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

    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)

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

    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

  • Active comparator
    Arm 2/Cohort 2: TAC + MMF ± Corticosteroids

    Patients received TAC-based regimen throughout the study.

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

Interventions

  • BiologicalCFZ533 - Cohort 1/Cohort 2

    CFZ533 was administered either by intravenous infusion or subcutaneous injection

  • DrugMycophenolate Mofetil (MMF)

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

  • DrugCorticosteroids (CS)

    Taken either orally or intravenously.

  • DrugTacrolimus

    Standard of care immunosuppressive regimen

  • DrugInduction therapy: basiliximab

    Lyophilized solution taken intravenously

  • DrugInduction therapy: rabbit anti-thymocyte globulin (rATG)

    Lyophilized vial taken intravenously.

    Also known as: Lyophilized solution

  • DrugMaintenance population: EC-MPS

    Tablet that is taken orally

  • DrugMaintenance population: MMF

    Tablet that is taken orally

  • DrugPlacebo 1 mL

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

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 12 Months

  2. 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.

    Time frame: 12 Months

Secondary outcomes

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

    In the de novo population (Cohort 1), the mean eGFR at Month 12 post-transplantation was the endpoint of interest. Estimated GFR using central laboratory serum creatinine values was calculated using the MDRD4 formula.

    Time frame: 12 months

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

    In the maintenance population (Cohort 2), a baseline kidney function and the mean change from baseline at Month 12 post-conversion of eGFR was the endpoint of interest. Estimated GFR using central laboratory serum creatinine values was calculated using the MDRD4 formula.

    Time frame: 12 months

  3. Free CFZ533 Plasma Concentrations Over Time (Cohort 1)

    Pharmacokinetics were determined for free CFZ533 plasma concentrations during the treatment period.

    Time frame: Day 1-Pre-Dose to Month 30-Pre-Dose

  4. Free CFZ533 Plasma Concentrations Over Time (Cohort 2)

    Pharmacokinetics were determined for free CFZ533 plasma concentrations during the treatment period.

    Time frame: Day 1-Pre-Dose to Month 30-Pre-Dose

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

    The presence of anti-CFZ533 antibodies was assessed using screening and confirmatory assays.

    Time frame: 24 Months

  6. Semi-quantiative Analysis of Anti-CFZ533 Antibodes in Plasma (CFZ533 Treated Patients Only) (Cohort 2)

    The presence of anti-CFZ533 antibodies was assessed using screening and confirmatory assays.

    Time frame: 24 Months

07

Results

Posted Mar 23, 2026
Limitations and caveats
One patient in Cohort 1 randomized to the TAC arm died one day after transplantation and did not take study drug.

Participant flow

Patients were enrolled at 74 sites. 403 patients were randomized.

Participant flow — Overall Study
MilestoneArm 1/Cohort 1 (De Novo Cohort): CFZ533 600 mg + Mycophenolate Mofetil (MMF) + CorticosteroidsArm 2/Cohort 1 (De Novo Cohort): CFZ533 300 mg + Mycophenolate Mofetil (MMF) + CorticosteroidsArm 3/Cohort 1 (De Novo Cohort): Control/Standard of Care: Tacrolimus (TAC) + MMF + CorticosteroidsArm 1/Cohort 2 (Maintenance Cohort): CFZ533 450 mg + MMF ± CorticosteroidsArm 2/Cohort 2 (Maintenance Cohort): TAC + MMF ± Corticosteroids
Started108109747042
Full analysis set108109747042
Pharmacokinetics analysis set1101090700
Completed00000
Not completed108109747042
Withdrew: Unsatisfactory therapeutic effect52100
Withdrew: Adverse event819360
Withdrew: Death91212
Withdrew: Lost to follow-up00100
Withdrew: Patient not continuing after month121291132
Withdrew: Physician decision00001
Withdrew: Study terminated by sponsor7173536033
Withdrew: Subject decision35304

Outcome measures

PrimaryPercentage 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.

Time frame:
12 Months
Reported as:
Number · Percentage of participants
Percentage of Participants With Composite Efficacy Failure Event (Biopsy Proven Acute Rejection (BPAR), Graft Loss or Death) Over 12 Months Post-transplantation (Cohort 1)
Percentage of participantsArm 1/Cohort 1 (De Novo Cohort): CFZ533 600 mg + Mycophenolate Mofetil (MMF) + CorticosteroidsArm 2/Cohort 1 (De Novo Cohort): CFZ533 300 mg + Mycophenolate Mofetil (MMF) + CorticosteroidsArm 3/Cohort 1 (De Novo Cohort): Control/Standard of Care: Tacrolimus (TAC) + MMF + Corticosteroids
Percentage of Participants With Composite Efficacy Failure Event (Biopsy Proven Acute Rejection (BPAR), Graft Loss or Death) Over 12 Months Post-transplantation (Cohort 1)60.638.622.0
Statistical analysis
  • Arm 1/Cohort 1 (De Novo Cohort): CFZ533 600 mg + Mycophenolate Mofetil (MMF) + Corticosteroids vs Arm 3/Cohort 1 (De Novo Cohort): Control/Standard of Care: Tacrolimus (TAC) + MMF + Corticosteroids · Rate difference: 15.80 · 95% CI 3.86 to 27.74
  • Arm 2/Cohort 1 (De Novo Cohort): CFZ533 300 mg + Mycophenolate Mofetil (MMF) + Corticosteroids vs Arm 3/Cohort 1 (De Novo Cohort): Control/Standard of Care: Tacrolimus (TAC) + MMF + Corticosteroids · Rate difference: 5.61 · 95% CI -5.67 to 16.90
PrimaryPercentage 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.

Time frame:
12 Months
Reported as:
Number · Percentage of participants
Percentage of Participants With Composite Efficacy Failure Event (BPAR, Graft Loss or Death) Over 12 Months Post-conversion (Cohort 2)
Percentage of participantsArm 1/Cohort 2 (Maintenance Cohort): CFZ533 450 mg + MMF ± CorticosteroidsArm 2/Cohort 2 (Maintenance Cohort): TAC + MMF ± Corticosteroids
Percentage of Participants With Composite Efficacy Failure Event (BPAR, Graft Loss or Death) Over 12 Months Post-conversion (Cohort 2)14.711.1
Statistical analysis
  • Arm 1/Cohort 2 (Maintenance Cohort): CFZ533 450 mg + MMF ± Corticosteroids · Rate difference: -1.43 · 95% CI -14.24 to 11.39
SecondaryCohort 1: Mean Estimated Glomerular Filtration Rate (eGFR) ((MDRD4) at 12 Months Post-transplantation

In the de novo population (Cohort 1), the mean eGFR at Month 12 post-transplantation was the endpoint of interest. Estimated GFR using central laboratory serum creatinine values was calculated using the MDRD4 formula.

Time frame:
12 months
Reported as:
Mean · mL/min/1.73m^2
Cohort 1: Mean Estimated Glomerular Filtration Rate (eGFR) ((MDRD4) at 12 Months Post-transplantation
mL/min/1.73m^2Arm 1/Cohort 1 (De Novo Cohort): CFZ533 600 mg + Mycophenolate Mofetil (MMF) + CorticosteroidsArm 2/Cohort 1 (De Novo Cohort): CFZ533 300 mg + Mycophenolate Mofetil (MMF) + CorticosteroidsArm 3/Cohort 1 (De Novo Cohort): Control/Standard of Care: Tacrolimus (TAC) + MMF + Corticosteroids
Cohort 1: Mean Estimated Glomerular Filtration Rate (eGFR) ((MDRD4) at 12 Months Post-transplantation58.83 ± 1.97160.63 ± 1.97654.12 ± 2.101
Statistical analysis
  • Arm 1/Cohort 1 (De Novo Cohort): CFZ533 600 mg + Mycophenolate Mofetil (MMF) + Corticosteroids vs Arm 3/Cohort 1 (De Novo Cohort): Control/Standard of Care: Tacrolimus (TAC) + MMF + Corticosteroids · ANOVA · p = 0.103 · Mean difference: 4.71 · 95% CI -0.96 to 10.38the ANOVA model adjusted by treatment group, donor category and induction therapy
  • Arm 2/Cohort 1 (De Novo Cohort): CFZ533 300 mg + Mycophenolate Mofetil (MMF) + Corticosteroids vs Arm 3/Cohort 1 (De Novo Cohort): Control/Standard of Care: Tacrolimus (TAC) + MMF + Corticosteroids · ANOVA · p = 0.025 · Mean difference: 6.51 · 95% CI 0.83 to 12.18the ANOVA model adjusted by treatment group, donor category and induction therapy
SecondaryCohort 2: Mean Change in Estimated Glomerular Filtration Rate (eGFR) ((MDRD4) at 12 Months Post-conversion

In the maintenance population (Cohort 2), a baseline kidney function and the mean change from baseline at Month 12 post-conversion of eGFR was the endpoint of interest. Estimated GFR using central laboratory serum creatinine values was calculated using the MDRD4 formula.

Time frame:
12 months
Reported as:
Mean · mL/min/1.73m^2
Cohort 2: Mean Change in Estimated Glomerular Filtration Rate (eGFR) ((MDRD4) at 12 Months Post-conversion
mL/min/1.73m^2Arm 1/Cohort 2 (Maintenance Cohort): CFZ533 450 mg + MMF ± CorticosteroidsArm 2/Cohort 2 (Maintenance Cohort): TAC + MMF ± Corticosteroids
Cohort 2: Mean Change in Estimated Glomerular Filtration Rate (eGFR) ((MDRD4) at 12 Months Post-conversion4.30 ± 1.7221.42 ± 1.866
Statistical analysis
  • Arm 1/Cohort 2 (Maintenance Cohort): CFZ533 450 mg + MMF ± Corticosteroids vs Arm 2/Cohort 2 (Maintenance Cohort): TAC + MMF ± Corticosteroids · ANOVA · p = 0.153 · Mean change difference: 2.88 · 95% CI -1.10 to 6.85ANCOVA model adjusted by baseline, treatment group, corticosteroid use, time since transplant
SecondaryFree CFZ533 Plasma Concentrations Over Time (Cohort 1)

Pharmacokinetics were determined for free CFZ533 plasma concentrations during the treatment period.

Time frame:
Day 1-Pre-Dose to Month 30-Pre-Dose
Reported as:
Mean · µg/mL
Free CFZ533 Plasma Concentrations Over Time (Cohort 1)
µg/mLArm 1/Cohort 1 (De Novo Cohort): CFZ533 600 mg + Mycophenolate Mofetil (MMF) + CorticosteroidsArm 2/Cohort 1 (De Novo Cohort): CFZ533 300 mg + Mycophenolate Mofetil (MMF) + CorticosteroidsArm 3/Cohort 1 (De Novo Cohort): Control/Standard of Care: Tacrolimus (TAC) + MMF + Corticosteroids
Day 1 Pre-dose0.00 ± 0.0000.00 ± 0.000—
Day 1 post-dose471.20 ± 222.169441.67 ± 246.474—
Day 5 pre-dose231.93 ± 102.947205.16 ± 77.632—
Day 5 post-dose502.48 ± 211.592502.32 ± 186.159—
Day 15 pre-dose251.17 ± 92.466242.99 ± 83.780—
Day 29 pre-dose197.47 ± 74.937187.38 ± 79.884—
Month 1.5 pre-dose172.84 ± 67.444122.80 ± 38.604—
Month 2 pre-dose155.68 ± 64.661102.52 ± 33.798—
Month 2.5 pre-dose151.81 ± 58.36785.21 ± 34.835—
Month 3 pre-dose147.62 ± 51.97186.16 ± 35.463—
Month 4 pre-dose159.58 ± 70.38268.72 ± 27.269—
Month 6 pre-dose161.21 ± 63.19573.27 ± 35.126—
Month 8 pre-dose151.34 ± 52.77871.92 ± 33.683—
Month 10 pre-dose141.18 ± 46.99962.55 ± 31.199—
Moth 12 pre-dose148.71 ± 62.10656.81 ± 30.717—
Month 15 pre-dose149.86 ± 58.88848.37 ± 20.604—
Month 18 pre-dose122.24 ± 54.05649.68 ± 31.768—
Month 21 pre-dose132.51 ± 65.14659.96 ± 36.583—
Month 24 pre-dose139.55 ± 53.17760.96 ± 31.988—
Month 30 pre-dose140.80 ± 47.33956.63 ± 23.195—
SecondaryFree CFZ533 Plasma Concentrations Over Time (Cohort 2)

Pharmacokinetics were determined for free CFZ533 plasma concentrations during the treatment period.

Time frame:
Day 1-Pre-Dose to Month 30-Pre-Dose
Reported as:
Mean · µg/mL
Free CFZ533 Plasma Concentrations Over Time (Cohort 2)
µg/mLArm 1/Cohort 2 (Maintenance Cohort): CFZ533 450 mg + MMF ± CorticosteroidsArm 2/Cohort 2 (Maintenance Cohort): TAC + MMF ± Corticosteroids
Day 1 Pre-dose0.00 ± 0.000—
Day 1 post-dose681.59 ± 698.086—
Day 15 pre-dose181.81 ± 72.297—
Day 29 pre-dose147.56 ± 43.749—
Month 1.5 pre-dose127.55 ± 39.794—
Month 2 pre-dose121.81 ± 44.801—
Month 2.5 pre-dose114.53 ± 44.759—
Month 3 pre-dose104.40 ± 42.563—
Month 4 pre-dose108.61 ± 51.790—
Month 6 pre-dose112.14 ± 46.932—
Month 8 pre-dose118.08 ± 42.868—
Month 10 pre-dose106.98 ± 53.798—
Moth 12 pre-dose111.05 ± 54.629—
Month 15 pre-dose104.11 ± 67.744—
Month 18 pre-dose115.59 ± 66.227—
Month 21 pre-dose116.89 ± 53.953—
Month 24 pre-dose111.03 ± 39.901—
Month 30 pre-dose132.97 ± 65.132—
SecondarySemi-quantiative Analysis of Anti-CFZ533 Antibodes in Plasma (CFZ533 Treated Patients Only) (Cohort 1)

The presence of anti-CFZ533 antibodies was assessed using screening and confirmatory assays.

Time frame:
24 Months
Reported as:
Number · Participants
Semi-quantiative Analysis of Anti-CFZ533 Antibodes in Plasma (CFZ533 Treated Patients Only) (Cohort 1)
ParticipantsArm 1/Cohort 1 (De Novo Cohort): CFZ533 600 mg + Mycophenolate Mofetil (MMF) + CorticosteroidsArm 2/Cohort 1 (De Novo Cohort): CFZ533 300 mg + Mycophenolate Mofetil (MMF) + Corticosteroids
Subject with an on-study result109108
Binding antibody positive at any time20
Subject with a result at baseline104101
Binding antibody positive at or before baseline00
Subject with a post-baseline result102103
Binding antibody positive post-baseline with a positive result at baseline00
Binding antibody positive post-baseline with a negative result at baseline20
SecondarySemi-quantiative Analysis of Anti-CFZ533 Antibodes in Plasma (CFZ533 Treated Patients Only) (Cohort 2)

The presence of anti-CFZ533 antibodies was assessed using screening and confirmatory assays.

Time frame:
24 Months
Reported as:
Number · Participants
Semi-quantiative Analysis of Anti-CFZ533 Antibodes in Plasma (CFZ533 Treated Patients Only) (Cohort 2)
ParticipantsArm 1/Cohort 2 (Maintenance Cohort): CFZ533 450 mg + MMF ± Corticosteroids
Subject with an on-study result70
Binding antibody positive at any time0
Subject with a result at baseline68
Binding antibody positive at or before baseline0
Subject with a post-baseline result69
Binding antibody positive post-baseline with a positive result at baseline0
Binding antibody positive post-baseline with a negative or no result at baseline0

Adverse events

Collected over Deaths were reported from randomization until end of study, up to approx. 2.9 years. Adverse Events were reported from first dose of study treatment until end of safety follow-up (14 weeks safety follow-up CFZ533 and 12 weeks safety follow-up for TAC) up to approx. 2.9 years.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Pre-treatment1/403 (0.2%)——
De Novo Cohort: CFZ533 600 mg + MMF + CS/On-treatment Period2/108 (1.9%)71/108 (65.7%)105/108 (97.2%)
De Novo Cohort: CFZ533 600 mg + MMF + CS/Post- Treatment Safety Follow-up Period5/108 (4.6%)18/108 (16.7%)20/108 (18.5%)
De Novo Cohort: CFZ533 600 mg + MMF + CS/Post- Treatment Survival Follow-up Period2/108 (1.9%)——
De Novo Cohort: CFZ533 300 mg + MMF + CS/On-treatment Period0/109 (0%)76/109 (69.7%)102/109 (93.6%)
De Novo Cohort: CFZ533 300 mg + MMF + CS/Post-treatment Safety Follow-up Period1/109 (0.9%)19/109 (17.4%)19/109 (17.4%)
De Novo Cohort: CFZ533 300 mg + MMF + CS/Post- Treatment Survival Follow-up Period0/109 (0%)——
De Novo Cohort: TAC + MMF + CS/On-treatment Period1/73 (1.4%)39/73 (53.4%)67/73 (91.8%)
De Novo Cohort: TAC + MMF + CS/Post-treatment Safety Follow-up Period0/73 (0%)3/73 (4.1%)4/73 (5.5%)
De Novo Cohort: TAC + MMF + CS/Post- Treatment Survival Follow-up Period0/73 (0%)——
Maintenance Cohort: CFZ533 450 mg + MMF +/- CS/On-treatment Period0/70 (0%)25/70 (35.7%)54/70 (77.1%)
Maintenance Cohort: CFZ533 450 mg + MMF +/- CS/Post-treatment Safety Follow-up Period1/70 (1.4%)4/70 (5.7%)4/70 (5.7%)
Maintenance Cohort: CFZ533 450 mg + MMF +/- CS/Post- Treatment Survival Follow-up Period0/70 (0%)——
Maintenance Cohort: TAC + MMF +/- CS/On-treatment Period1/42 (2.4%)11/42 (26.2%)26/42 (61.9%)
Maintenance Cohort: TAC + MMF +/- CS/Post-treatment Safety Follow-up Period1/42 (2.4%)1/42 (2.4%)0/42 (0%)
Maintenance Cohort: TAC + MMF +/- CS/Post- Treatment Survival Follow-up Period0/42 (0%)——
Most frequent serious events
Showing 10 of 225
Most frequent serious events
EventPre-treatmentDe Novo Cohort: CFZ533 600 mg + MMF + CS/On-treatment PeriodDe Novo Cohort: CFZ533 600 mg + MMF + CS/Post- Treatment Safety Follow-up PeriodDe Novo Cohort: CFZ533 600 mg + MMF + CS/Post- Treatment Survival Follow-up PeriodDe Novo Cohort: CFZ533 300 mg + MMF + CS/On-treatment PeriodDe Novo Cohort: CFZ533 300 mg + MMF + CS/Post-treatment Safety Follow-up PeriodDe Novo Cohort: CFZ533 300 mg + MMF + CS/Post- Treatment Survival Follow-up PeriodDe Novo Cohort: TAC + MMF + CS/On-treatment PeriodDe Novo Cohort: TAC + MMF + CS/Post-treatment Safety Follow-up PeriodDe Novo Cohort: TAC + MMF + CS/Post- Treatment Survival Follow-up PeriodMaintenance Cohort: CFZ533 450 mg + MMF +/- CS/On-treatment PeriodMaintenance Cohort: CFZ533 450 mg + MMF +/- CS/Post-treatment Safety Follow-up PeriodMaintenance Cohort: CFZ533 450 mg + MMF +/- CS/Post- Treatment Survival Follow-up PeriodMaintenance Cohort: TAC + MMF +/- CS/On-treatment PeriodMaintenance Cohort: TAC + MMF +/- CS/Post-treatment Safety Follow-up PeriodMaintenance Cohort: TAC + MMF +/- CS/Post- Treatment Survival Follow-up Period
Transplant rejectionImmune system disorders—16/1080/108—10/1091/109—6/730/73—2/700/70—0/420/42—
Cytomegalovirus infectionInfections and infestations—16/1082/108—11/1093/109—0/730/73—0/700/70—1/420/42—
Acute kidney injuryRenal and urinary disorders—3/1083/108—4/1091/109—7/730/73—1/700/70—1/420/42—
Urinary tract infectionInfections and infestations—5/1081/108—6/1090/109—6/730/73—5/700/70—1/420/42—
PyrexiaGeneral disorders—4/1080/108—5/1093/109—1/730/73—4/700/70—0/420/42—
Delayed graft functionInjury, poisoning and procedural complications—6/1080/108—3/1090/109—4/730/73—0/700/70—0/420/42—
COVID-19Infections and infestations—5/1080/108—3/1090/109—3/730/73—1/700/70—2/420/42—
PneumoniaInfections and infestations—3/1081/108—0/1091/109—1/731/73—0/702/70—2/420/42—
Squamous cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)—1/1080/108—1/1090/109—0/730/73—0/700/70—2/420/42—
Polyomavirus-associated nephropathyInfections and infestations—0/1082/108—5/1090/109—0/730/73—0/700/70—0/420/42—
Most frequent other events
Showing 10 of 74
Most frequent other events
EventPre-treatmentDe Novo Cohort: CFZ533 600 mg + MMF + CS/On-treatment PeriodDe Novo Cohort: CFZ533 600 mg + MMF + CS/Post- Treatment Safety Follow-up PeriodDe Novo Cohort: CFZ533 600 mg + MMF + CS/Post- Treatment Survival Follow-up PeriodDe Novo Cohort: CFZ533 300 mg + MMF + CS/On-treatment PeriodDe Novo Cohort: CFZ533 300 mg + MMF + CS/Post-treatment Safety Follow-up PeriodDe Novo Cohort: CFZ533 300 mg + MMF + CS/Post- Treatment Survival Follow-up PeriodDe Novo Cohort: TAC + MMF + CS/On-treatment PeriodDe Novo Cohort: TAC + MMF + CS/Post-treatment Safety Follow-up PeriodDe Novo Cohort: TAC + MMF + CS/Post- Treatment Survival Follow-up PeriodMaintenance Cohort: CFZ533 450 mg + MMF +/- CS/On-treatment PeriodMaintenance Cohort: CFZ533 450 mg + MMF +/- CS/Post-treatment Safety Follow-up PeriodMaintenance Cohort: CFZ533 450 mg + MMF +/- CS/Post- Treatment Survival Follow-up PeriodMaintenance Cohort: TAC + MMF +/- CS/On-treatment PeriodMaintenance Cohort: TAC + MMF +/- CS/Post-treatment Safety Follow-up PeriodMaintenance Cohort: TAC + MMF +/- CS/Post- Treatment Survival Follow-up Period
AnaemiaBlood and lymphatic system disorders—36/1080/108—23/1091/109—12/732/73—4/701/70—3/420/42—
HypertensionVascular disorders—36/1081/108—29/1090/109—15/731/73—12/700/70—1/420/42—
LeukopeniaBlood and lymphatic system disorders—31/1084/108—31/1094/109—16/731/73—9/702/70—1/420/42—
ConstipationGastrointestinal disorders—30/1082/108—21/1091/109—12/730/73—3/700/70—1/420/42—
DiarrhoeaGastrointestinal disorders—19/1085/108—25/1094/109—20/730/73—11/701/70—4/420/42—
Urinary tract infectionInfections and infestations—19/1083/108—27/1092/109—17/731/73—5/700/70—2/420/42—
HyperkalaemiaMetabolism and nutrition disorders—18/1081/108—8/1090/109—18/730/73—1/700/70—1/420/42—
HyperglycaemiaMetabolism and nutrition disorders—12/1084/108—16/1090/109—17/730/73—1/702/70—1/420/42—
Oedema peripheralGeneral disorders—21/1083/108—13/1091/109—7/730/73—4/700/70—1/420/42—
HypokalaemiaMetabolism and nutrition disorders—21/1083/108—13/1090/109—3/730/73—1/701/70—1/420/42—

Baseline characteristics

Full Analysis Set (FAS): all patients who received transplantation and randomized, excluding mis-randomized patients. Mis-randomized patients were defined as cases where IRT contacts were made by the Investigator/qualified site staff either prematurely or inappropriately for confirmation of the patient's final randomization eligibility and treatment was not administered to the patient.

Age, Customized
Age, Customized(Participants)Arm 1/Cohort 1 (De Novo Cohort): CFZ533 600 mg + Mycophenolate Mofetil (MMF) + CorticosteroidsArm 2/Cohort 1 (De Novo Cohort): CFZ533 300 mg + Mycophenolate Mofetil (MMF) + CorticosteroidsArm 3/Cohort 1 (De Novo Cohort): Control/Standard of Care: Tacrolimus (TAC) + MMF + CorticosteroidsArm 1/Cohort 2 (Maintenance Cohort): CFZ533 450 mg + MMF ± CorticosteroidsArm 2/Cohort 2 (Maintenance Cohort): TAC + MMF ± CorticosteroidsTotal
< 60 years8679545332304
>= 60 6years223020171099
Sex: Female, Male
Sex: Female, Male(Participants)Arm 1/Cohort 1 (De Novo Cohort): CFZ533 600 mg + Mycophenolate Mofetil (MMF) + CorticosteroidsArm 2/Cohort 1 (De Novo Cohort): CFZ533 300 mg + Mycophenolate Mofetil (MMF) + CorticosteroidsArm 3/Cohort 1 (De Novo Cohort): Control/Standard of Care: Tacrolimus (TAC) + MMF + CorticosteroidsArm 1/Cohort 2 (Maintenance Cohort): CFZ533 450 mg + MMF ± CorticosteroidsArm 2/Cohort 2 (Maintenance Cohort): TAC + MMF ± CorticosteroidsTotal
Female3432141814112
Male7477605228291
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Arm 1/Cohort 1 (De Novo Cohort): CFZ533 600 mg + Mycophenolate Mofetil (MMF) + CorticosteroidsArm 2/Cohort 1 (De Novo Cohort): CFZ533 300 mg + Mycophenolate Mofetil (MMF) + CorticosteroidsArm 3/Cohort 1 (De Novo Cohort): Control/Standard of Care: Tacrolimus (TAC) + MMF + CorticosteroidsArm 1/Cohort 2 (Maintenance Cohort): CFZ533 450 mg + MMF ± CorticosteroidsArm 2/Cohort 2 (Maintenance Cohort): TAC + MMF ± CorticosteroidsTotal
White8486594732308
Black or African American14663433
Asian: Indian200103
Asian: Japanese412312435
Asian: Korean100304
Asian: Other012115
American Indian or Alaskan Native001001
Multiple3432113
Other - Unknown000101
08

Study locations

74 sites
  • Novartis Investigative Site
    Los Angeles, California 90033, United States
  • Novartis Investigative Site
    San Francisco, California 94143 0116, United States
  • Novartis Investigative Site
    Aurora, Colorado 80045, United States
  • Novartis Investigative Site
    Chicago, Illinois 60611, United States
  • Novartis Investigative Site
    Chicago, Illinois 60612, United States
  • Novartis Investigative Site
    Kansas City, Kansas 66103, United States
  • Novartis Investigative Site
    Baltimore, Maryland 21201, United States
  • Novartis Investigative Site
    Boston, Massachusetts 02114, United States
  • Novartis Investigative Site
    Detroit, Michigan 48202 2689, United States
  • Novartis Investigative Site
    St Louis, Missouri 63110, United States
  • Novartis Investigative Site
    Durham, North Carolina 27710, United States
  • Novartis Investigative Site
    Cincinnati, Ohio 45219, United States
  • Novartis Investigative Site
    Cincinnati, Ohio 45267-0585, United States
  • Novartis Investigative Site
    Dallas, Texas 75390, United States
  • Novartis Investigative Site
    Seattle, Washington 98195, United States
  • Novartis Investigative Site
    Buenos Aires, W3400ABH, Argentina
  • Novartis Investigative Site
    Corrientes, W3400, Argentina
  • Novartis Investigative Site
    Córdoba, X5016KEH, Argentina
  • Novartis Investigative Site
    Camperdown, New South Wales 2050, Australia
  • Novartis Investigative Site
    Adelaide, South Australia 5000, Australia
  • Novartis Investigative Site
    Clayton, Victoria 3168, Australia
  • Novartis Investigative Site
    Leuven, 3000, Belgium
  • Novartis Investigative Site
    Porto Alegre, Rio Grande do Sul 90020-090, Brazil
  • Novartis Investigative Site
    São Paulo, São Paulo 04038-002, Brazil
  • Novartis Investigative Site
    São Paulo, São Paulo 05403 000, Brazil
  • Novartis Investigative Site
    Vancouver, British Columbia V6Z 1Y6, Canada
  • Novartis Investigative Site
    Prague, 146 24, Czechia
  • Novartis Investigative Site
    Bordeaux, 33076, France
  • Novartis Investigative Site
    Créteil, 94010, France
  • Novartis Investigative Site
    Grenoble, 38043, France
  • Novartis Investigative Site
    Lyon, 69003, France
  • Novartis Investigative Site
    Nantes, 44093, France
  • Novartis Investigative Site
    Paris, 75015, France
  • Novartis Investigative Site
    Toulouse, 31054, France
  • Novartis Investigative Site
    Tours, 37044, France
  • Novartis Investigative Site
    Regensburg, Bavaria 93053, Germany
  • Novartis Investigative Site
    Berlin, 13353, Germany
  • Novartis Investigative Site
    Dresden, 01307, Germany
  • Novartis Investigative Site
    Erlangen, 91054, Germany
  • Novartis Investigative Site
    Essen, 45147, Germany
  • Novartis Investigative Site
    Hamburg, 20246, Germany
  • Novartis Investigative Site
    Heidelberg, 69120, Germany
  • Novartis Investigative Site
    Mainz, 55131, Germany
  • Novartis Investigative Site
    Budapest, H-1083, Hungary
  • Novartis Investigative Site
    Debrecen, 4032, Hungary
  • Novartis Investigative Site
    Milan, MI 20132, Italy
  • Novartis Investigative Site
    Roma, RM 00133, Italy
  • Novartis Investigative Site
    Nagakute, Aichi-ken 480-1195, Japan
  • Novartis Investigative Site
    Nagoya, Aichi-ken 466-8650, Japan
  • Novartis Investigative Site
    Sapporo, Hokkaido 060 8648, Japan
  • Novartis Investigative Site
    Sapporo, Hokkaido 060-8604, Japan
  • Novartis Investigative Site
    Yokohama, Kanagawa 232 0024, Japan
  • Novartis Investigative Site
    Tomigusuku, Okinawa 9010224, Japan
  • Novartis Investigative Site
    Suita, Osaka 565 0871, Japan
  • Novartis Investigative Site
    Kumamoto, 861-8520, Japan
  • Novartis Investigative Site
    Osaka, 545-8586, Japan
  • Novartis Investigative Site
    Riga, LV 1002, Latvia
  • Novartis Investigative Site
    Rotterdam, South Holland 3015 GD, Netherlands
  • Novartis Investigative Site
    Groningen, 9713 GZ, Netherlands
  • Novartis Investigative Site
    Utrecht, 3584CX, Netherlands
  • Novartis Investigative Site
    Oslo, 0424, Norway
  • Novartis Investigative Site
    Seoul, 03080, South Korea
  • Novartis Investigative Site
    Palma de Mallorca, Balearic Islands 07120, Spain
  • Novartis Investigative Site
    L'Hospitalet de Llobregat, Barcelona 08907, Spain
  • Novartis Investigative Site
    Barcelona, Catalonia 08003, Spain
  • Novartis Investigative Site
    Barcelona, Catalonia 08035, Spain
  • Novartis Investigative Site
    Barcelona, Catalonia 08036, Spain
  • Novartis Investigative Site
    Zaragoza, 50009, Spain
  • Novartis Investigative Site
    Gothenburg, 413 45, Sweden
  • Novartis Investigative Site
    Uppsala, 751 85, Sweden
  • Novartis Investigative Site
    Bern, 3010, Switzerland
  • Novartis Investigative Site
    Glasgow, G51 4TF, United Kingdom
  • Novartis Investigative Site
    London, SW17 0QT, United Kingdom
  • Novartis Investigative Site
    Manchester, M13 9WL, United Kingdom
09

References and documents

Study documents

  • Study protocol · Mar 18, 2021
  • Statistical analysis plan · Feb 8, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 23, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03663335
Lead sponsor
Novartis Pharmaceuticals
Responsible party
Sponsor
First posted
Sep 10, 2018
Start date
Nov 28, 2018
Primary completion
Oct 29, 2021
Completion
Oct 29, 2021
Results posted
Mar 23, 2026
Last update
Mar 23, 2026

Study contacts

Novartis Pharmaceuticals
study director · Novartis Pharmaceuticals

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Feb 2026. You cannot join it, but the record below documents what was studied.

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