Efficacy, Safety and PK/PD of MOR202 in Anti-PLA2R + Membranous Nephropathy (aMN) (NewPLACE)

Study Overview
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Brief Summary
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This 2-arm, multi-center, open-label, parallel-group phase II trial will assess the efficacy, safety and pharmacokinetics/pharmacodynamics of the human antibody MOR202 in subjects with anti-PLA2R antibody-positive membranous nephropathy indicated for immunosuppressive therapy

Detailed Description
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After treatment, subjects will enter a repeat treatment period (3 months) if necessary; and a final follow-up period of 15 to 18 months

Official Title
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A Phase IIa, Open-Label, 2-Arm Multicenter Clinical Trial to Evaluate the Efficacy, Safety and PK/PD of the Human Anti-CD38 Antibody MOR202 in Anti-PLA2R Antibody Positive Membranous Nephropathy (NewPLACE)

Conditions
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Glomerulonephritis, Membranous Nephropathy, antiPLA2R Positive

Intervention / Treatment
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* Drug: MOR202


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects > 18 to < 80 years (at date of signing the informed consent form [ICF]). Urine protein to creatinine ratio (UPCR) of > 3.0 g/g or proteinuria > 3.5 g/24 h Estimated glomerular filtration rate (eGFR) > 50 ml/min/1.73 m² (eGFR >30 and < 50 ml/min/1.73 m² can be included provided an interstitial fibrosis and tubular atrophy (IFTA) score of < 25% in a kidney biopsy) Not in spontaneous remission despite proper treatment with angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARBs) (sufficient dose and treatment duration) as per clinical practice and scientific guidelines. If the subject is intolerant to ACEI and ARBs, the reason must be documented and approval for enrollment be obtained from the Medical Monitor. Systolic blood pressure (BP) <150 mmHg and diastolic BP <100 mmHg after 5 minutes of rest. Serum anti-PLA2R antibodies > 50.0 RU/mL determined by Euroimmun ELISA. Female subjects: A female is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Not a female of childbearing potential (FCBP) A FCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 3 months after the last dose of MOR202 Key Exclusion Criteria: Hemoglobin < 80 g/L. Thrombocytopenia: Platelets < 100.0 x 109/L. Neutropenia: Neutrophils < 1.5 x 109/L. Leukopenia: Leukocytes < 3.0 x 109/L. Hypogammaglobulinemia: Serum immunoglobulins ≤ 4.0 g/L. Subjects may receive supportive therapies to meet the above criteria B-cells < 5 x 106/L Diabetes mellitus type 2: Subjects with type 2 diabetes mellitus may only enter the clinical trial if a kidney biopsy performed within 6 months prior to screening shows MN without evidence of diabetic nephropathy and diabetes is controlled, as shown by: Glycated hemoglobin (HbAlc) <8.0 % or 64 mmol/mol. No diabetic retinopathy known. No peripheral neuropathy known. Total bilirubin, aspartate aminotransferase or alanine aminotransferase >1.5 x ULN, alkaline phosphatase >3.0 x ULN.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MOR202 Arm 1<br>5 doses administered on Day 1, 8, 15, 29, and 57 | Drug: MOR202<br>* 5 or 2 doses of MOR202 will be administered as an intravenous infusion<br>|
| Experimental: MOR202 Arm 2<br>2 doses administered on Day 1 and 15 | Drug: MOR202<br>* 5 or 2 doses of MOR202 will be administered as an intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| efficacy: percent change of anti-PLA2R antibody levels | efficacy of 2 different dosing regimens of MOR202 in subjects with anti-PLA2R antibody positive MN | 3 months compared to baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| efficacy: immunological complete response (ICR) rate | efficacy of 2 different dosing regimens of MOR202 | ICR rate at 3 months, 6 months, 12 months and 24 months | 
| efficacy: overall proteinuria response (OPR) rate | efficacy of 2 different dosing regimens of MOR202 | OPR rate at 6 months, 12 months and 24 months. | 
| safety: determined by the frequency, incidence and severity of TEAEs | frequency, incidence and severity of treatment-emergent adverse events | through treatment completion, an average of 3 months per treatment period | 
| PK profile | MOR202 serum concentrations after multiple i.v. administrations | through study completion, an average of 1 year | 
| immunogenicity | number of subjects developing anti-MOR202 antibodies | through study completion, an average of 1 year |