Clinical Trial to Assess Efficacy and Safety of the Human Anti-CD38 Antibody Felzartamab (MOR202) in IgA Nephropathy

Proteinuria is high levels of protein in the urine and is measured by UPCR. Relative change in UPCR was estimated based on mixed effects model for repeated measure (MMRM) model. Least squares (LS) mean and standard error (SE) were reported. The reference proteinuria value before start of treatment is defined as the mean of the values determined at screening and prior to baseline (visit 2) predose (UPCR from 24h urine). Negative change from baseline indicates less proteinuria.

All felzartamab and placebo-treated participants with evaluable IgA data and felzartamab serum concentrations (in felzartamab-treated participants only) were divided into exposure quartiles using the sum of measurable felzartamab Ctrough values up to 9 months after the first dose. Percent change from baseline in IgA concentration in these participants was summarized as per each serum concentration quartile.

All participants with evaluable maximum felzartamab concentrations after the first dose were included in the analysis. Cmax values were assessed by infusion-related reaction status after the first dose.

Proteinuria is high levels of protein in the urine and is measured by UPCR. Relative change in UPCR will be estimated based on an MMRM model. The reference proteinuria value before start of treatment is defined as the mean of the values determined at screening and prior to baseline (visit 2) predose (UPCR from 24h urine). Negative change from baseline indicates less proteinuria.

CR was defined as the reduction of proteinuria to less than 0.3 g/g UPCR, serum albumin within the reference range of the central laboratory and stable estimated glomerular filtration rate (eGFR) (at least 80% of value at baseline visit).

Response was defined as reduction of proteinuria to below 0.6 g/g (UPCR) and stable eGFR (at least 80% of value at baseline visit), but not CR.

Duration of response was defined as date of 1st observation of progressive disease minus date of 1st observation of response+1 day. Duration of response was estimated by Kaplan Meier method.

Time to response was defined as date of 1st observation of response minus date of randomization+1 day. Time to response was estimated by Kaplan Meier method.

eGFR was calculated as per the chronic kidney disease epidemiology collaboration (CKD-EPI) equation. eGFR =141×min(Scr/κ, 1)α×max(Scr κ,1)-1.209×0.993Age ×1.018[if female]×1.159 [if black] where:

• Scr is serum creatinine in μmol/L,
• κ is 61.9 for females and 79.6 for males,
• α is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/κ or 1, and max indicates the maximum of Scr/κ or 1 eGFR as a measure of kidney function. eGFR was calculated in terms of milliliter per minute per 1.73 meter square (mL/min/1.73 m^2). A numerically smaller negative change in eGFR indicates a slowing in kidney disease progression.

TEAEs were defined as any AEs reported after the start of trial treatment until 28 days after the last trial treatment, defined as the treatment-emergent period. TESAEs were TEAEs that met the following criteria: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition.

Blood samples were collected for measurement of anti-felzartamab antibodies in the serum. Number of participants with Anti-drug antibody (ADA) status positive/negative was summarized.