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.
The study was designed as a randomized, 36-month clinical trial comprised of: * A screening period (up to 2 months) starting from informed consent, screening visit, and including successful liver transplantation (LTx). * A run-in treatment period following successful transplantation that ended on the day of randomization or randomization failure, at Day 8 (with visit window of +/- 2 days) post-LTx. * The primary treatment period (Treatment Period 1) starting at randomization Day 8 +/- 2 post-LTx up to Month 12 followed by a 12-month follow-up treatment period (Treatment Period 2) until Month 24. * The long-term extension period (Treatment Period 3) starting post Month 24 until the end of the study (EOS). * A minimum 12-week safety follow-up period for all patients after EOS. The study was terminated following less favorable efficacy by Iscalimab (CFZ533) in liver transplant patients compared to tacrolimus.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
129
Comparison with standard of care immunosuppression
Standard of care immunosuppresive regimen
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.
Time frame: Baseline to Month 12
Mean Change in Estimated Glomerular Filtration Rate (eGFR) From Randomization to Month 12
Renal function as measured by estimated Glomerular Filtration Rate (eGFR) was evaluated using the MDRD formula: eGFR = 175 x (serum concentration of creatinine (SCr))-1.154 x (age)-0.203 x 0.742 \[if female\] x 1.212 \[if Black\].
Time frame: Baseline to Month 12
Number of Participants With Treatment Emergent Adverse Events
The distribution of adverse events was done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs), Deaths due to AEs and TEAEs leading to discontinuation, through the monitoring of relevant clinical and laboratory safety parameters.
Time frame: 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
The number and percentage of participants with dose changes (MMF and TAC), dose interruptions (only in cases of ascites drainage), and permanent discontinuation was summarized. In the CFZ533 arms, during the immediate peri and post-transplant period, TAC was given to provide immunological coverage but TAC needed to be completely weaned off by Day 22.
Time frame: Baseline to Month 24
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