Trial to Assess Safety and Efficacy of MOR202 in Anti-PLA2R + Membranous Nephropathy (aMN)

Study Overview
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Brief Summary
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This is an open-label, multicentre study to characterize the safety and efficacy of the human anti-CD38 antibody MOR202 in adult subjects with in Anti-PLA2R Antibody Positive Membranous Nephropathy (newly diagnosed/relapsed/refractory)

Detailed Description
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After treatment subjects will be observed for up to 1 year.

Official Title
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A Phase Ib/IIa, Open-Label, Multicenter Clinical Trial to Assess Safety and Efficacy of the Human Anti-CD38 Antibody MOR202 in Anti-PLA2R Antibody Positive Membranous Nephropathy (aMN)

Conditions
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Glomerulonephritis, Membranous, antiPLA2R Positive

Intervention / Treatment
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* Drug: MOR202


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: > 18 to < 80 years (at date of signing informed consent form [ICF]). Urine protein to creatinine ratio (UPCR) of ≥ 3.000 g/g OR proteinuria ≥ 3.500 g/24 h from 24-h urine at screening Active anti-PLA2R antibody positive MN in need of immunosuppressive therapy (IST) according to investigator judgement and diagnosed on the basis of a biopsy, archival biopsy acquired within 5 years prior to screening is acceptable. Estimated glomerular filtration rate ≥ 50 ml/min/1.73m² or ≥ 30 and <50 ml/min/1.73m², and interstitial fibrosis and tubular atrophy score of less than 25% on a renal biopsy obtained within the last 6 months prior to start of screening. Not in spontaneous remission despite proper treatment with ACEIs, ARBs (sufficient dose and treatment duration) as per clinical practice and scientific guidelines. If the subject is intolerant to an ACEI or ARB, the reason must be documented and approval obtained prior to enrolment. Systolic blood pressure BP ≤150 mmHg and diastolic BP ≤100 mmHg after 5 minutes of rest Vaccinated against Pneumococcus within the last 3 years prior to date of signing informed consent (subjects may be vaccinated during screening to meet this criterion; interval to first dose of MOR202 must be at least 14 days). Cohort 1 comprises newly diagnosed or relapsed subjects: Serum anti-PLA2R antibodies ≥50.0 RU/mL Cohort 2 comprises therapy refractory subjects: a Subject did not achieve immunological remission after prior IST(s) as documented by the investigator AND b Subject is without promising standard therapeutic options as documented by the investigator (i.e. investigator expects efficacy or safety issues with remaining IST options) AND c Serum anti-PLA2R antibodies ≥ 20.0 RU/mL measured at screening Note: France will only enroll patients in Cohort 2. 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. Secondary cause of MN (e.g. Systemic lupus erythematosus, medications, malignancies) Concomitant renal disease other than MN (e.g., diabetic renal disease, lupus nephritis, IgA nephropathy).

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: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: 2 cohorts by disease status (Cohort 1: Patients with newly diagnosed or relapsed membranous nephropathy; Cohort 2: Patients with membranous nephropathy refractory to immunosuppressive treatment)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Patients with newly diagnosed or relapsed membranous nephropathy | Drug: MOR202<br>* Patients will receive 9 doses of MOR202 as an intravenous infusion over 6 treatment cycles of 28-days each. Dosing will occur weekly in Cycle 1 and every 4 weeks in Cycles 2 to 6.<br>|
| Experimental: Cohort 2<br>Patients with membranous nephropathy refractory to immunosuppressive treatment | Drug: MOR202<br>* Patients will receive 9 doses of MOR202 as an intravenous infusion over 6 treatment cycles of 28-days each. Dosing will occur weekly in Cycle 1 and every 4 weeks in Cycles 2 to 6.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety and tolerability: incidence and severity of treatment-emergent adverse events | incidence and severity of treatment-emergent adverse events | at end of treatment phase (after 6 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| effect of MOR202 on serum anti-PLA2R antibodies | best Immunological Response based on reduction of serum anti-PLA2R antibody titer | through study completion, an average of 1 year | 
| immunogenicity of MOR202 | number of subjects developing anti-MOR202 antibodies | through study completion, an average of 1 year | 
| PK profile | serum concentrations after multiple i.v. administrations | through study completion, an average of 1 year | 
| safety in the follow-up phase: incidence and severity of adverse events (AEs) in the follow-up phase | incidence and severity of adverse events (AEs) in the follow-up phase | through study completion, an average of 1 year |