E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary (anti-PLA2R antibody positive) Membranous Nephropathy |
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E.1.1.1 | Medical condition in easily understood language |
Membranous Nephropathy (a condition of the kidneys). |
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E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027170 |
E.1.2 | Term | Membranous nephropathy |
E.1.2 | System Organ Class | 100000004857 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the safety and tolerability of MOR202 treatment in subjects with anti-PLA2R antibody positive membranous nephropathy (aMN) |
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E.2.2 | Secondary objectives of the trial |
To assess the effect of MOR202 on serum anti-PLA2R antibodies in subjects with aMN To assess immunogenicity of MOR202 (anti-MOR202 antibody formation) To assess the pharmacokinetic (PK) profile of MOR202 To assess safety in the follow-up phase |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. ≥18 to ≤80 years (at date of signing ICF) 2. Urine protein to creatinine ratio (UPCR) of ≥ 3.0 g/g (as measured from a 24 hour urine collection) 3. MN diagnosed on the basis of a biopsy, archival biopsy acquired within 5 years prior to screening is acceptable. 4. Estimated glomerular filtration rate (eGFR) ≥50 ml/min/1.73m² or >30 and <50 ml/min/1.73m², and IFTA (interstitial fibrosis and tub-ular atrophy) score of less than 25% on a renal biopsy obtained within the last 6 months prior to start of screening. If a subject falls into the latter range without availability of an adequate biopsy, a biopsy at screening should be performed for IFTA assessment. 5. The subject is on supportive treatment with an ACEI or an ARB for at least 4 weeks prior to screening. The ACEI or ARB treatment should have reached a stable dose according to best local practice. 6. Systolic BP ≤ 150 mmHg and diastolic BP ≤ 100 mmHg after a period of 5 minutes of rest as measured at screening 7. Subject vaccinated against Pneumococcus within the last 3 years prior to date of signing ICF (subjects may be vaccinated during screening to meet this criterion; interval to first dose of MOR202 must be at least 14 days (1)). 8. Cohort 1: Serum anti-PLA2R antibodies ≥ 150.0 RU/mL as determined at screening by Euroimmun ELISA 9. Cohort 1: Serum anti-PLA2R antibodies before screening ris-ing or stable as judged by the investigator 10. Cohort 1, relapse subjects only: Must have had complete remission of proteinuria, or a combination of partial remission of proteinuria (demonstrating at least 50 % decrease) with a remission of serum anti-PLA2R anti-body titer to less than 20.0 RU/mL (Euroimmun ELISA) or negative Immunfluorescence Test (IFT). Remission must have lasted for at least 6 months according to clinical judgement. 11. Cohort 2: Failure of previous therapy, i.e. subject never achieved a reduction of serum anti-PLA2R antibody titers to below 20.0 RU/ml (Euroimmun ELISA) during or after completion of a recognized IST contain-ing CSA, tacrolimus, MMF, ACTH or alkylating agents (e.g. cy-clophosphamide), or RTX determined after at least 6 months after start of this IST. 12. Cohort 2: Subjects may have received a maximum of two prior treatment lines of immunosuppressive therapy (retreatment for re-lapse with the same regimen is considered a line of its own). A planned, fixed sequence of different therapeutic agents (e. g. STARMEN regimen) is considered as one regimen. |
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E.4 | Principal exclusion criteria |
1. Hemoglobin < 90 g/L 2. Thrombocytopenia: Platelets < 100.0x10^9/L 3. Neutropenia: Neutrophils < 1.5x10^9/L 4. Leukopenia: Leukocytes < 3.0x10^9/L 5. Hypogammaglobulinemia: Serum immunoglobulins ≤5.0 g/L 6. Secondary cause of MN (e.g. SLE, medications, malignancies) as determined by the investigator 7. Concomitant renal disease other than MN (e.g., diabetic renal disease, lupus nephritis, IgA nephropathy) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Incidence and severity of treatment-emergent adverse events (TEAE) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
KEY SECONDARY ENDPOINT: Best Immunological Response: rate of sICR, ICR and IPR based on re-duction of serum anti-PLA2R antibody titer SECONDARY ENDPOINTS: 1. Number and antibody titers of subjects tested positive for anti-MOR202 antibodies 2. MOR202 serum concentrations after multiple i.v. administrations 3. Incidence and severity of AEs in the follow-up phase |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 33 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
European Union |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |