Safety, Tolerability and Efficacy of the Therapeutic Antibody Felzartamab in Rejection Late After Kidney Transplantatio

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 22

Inclusion Criteria

Voluntary written informed consent
Age >18 years (maximum: 70 years)
Functioning living or deceased donor allograft after =180 days post-transplantation
eGFR =20 ml/min/1.73 m2 (CKD-EPI formula)
HLA class I and/or II antigen-specific antibodies (preformed and/or de novo DSA).
Active or chronic/active ABMR (±C4d in PTC) according to the Banff 2019 classification
Molecular ABMR score (MMDx) =0.2
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 16
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 6

Exclusion Criteria

Patients actively participating in another clinical trial
Age =18 years
Female subject is pregnant or lactating or not on adequate contraceptive therapy
ABO-incompatible transplant
Index biopsy results:
T-cell-mediated rejection classified Banff grade =I
De novo or recurrent severe thrombotic microangiopathy
Polyoma virus nephropathy
De novo or recurrent glomerulonephritis
Acute rejection treatment =3 month before screening
Previous treatment with other CD38 monoclonal antibodies (e.g. daratumumab)
Previous treatment with other immunomodulatory monoclonal/polyclonal antibodies (e.g. CD20 Ab rituximab, IL-6/IL-6R Ab) =3 months before study treatment
Total bilirubin >2×the upper limit of normal [ULN], alanine transaminase and aspartate aminotransferase >2·5×ULN
Haemoglobin <8 g/dL
Thrombocytopenia: Platelets <100 G/L
Leukopenia: Leukocytes <3 G/L
Neutropenia: Neutrophils < 1.5 G/L
Hypogammaglobulinemia: Serum IgG <400 mg/dL
Active viral, bacterial or fungal infection precluding intensified immunosuppression
Active malignant disease precluding intensified immunosuppressive therapy
Latent or active tuberculosis (positive QuantiFERON-TB-Gold test)
Administration of a live vaccine within 6 weeks of screening
History of alcohol or illicit substance abuse
Serious medical or psychiatric illness likely to interfere with participation in the study

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The main objective of the trial is to evaluate the safety and tolerability of CD38 monoclonal antibody felzartamab in a prospective cohort of kidney transplant recipients diagnosed with late active or chronic active ABMR. ;Secondary Objective: The trial will evaluate preliminary efficacy of targeting CD38 in late active ABMR (secondary endpoints), and can be expected to provide a valuable basis for the potential design of a pivotal trial powered for the detection of clinical outcome differences.;Primary end point(s): Safety and tolerability of felzartamab in renal allograft recipients with ABMR on baseline immunosuppression;Timepoint(s) of evaluation of this end point: Over the study period of 52 weeks

Secondary Outcome Measures

Name	Time	Method

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