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. Active and anti-PLA2R antibody positive MN in need for IST according to investigator judgement and with diagnostic 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 1a (newly diagnosed patients): Serum anti-PLA2R antibodies ≥150.0 RU/mL determined at screening by Euroimmun ELISA. 9. Cohort 1b (relapse subjects): Must have had complete immunological and/or clinical remission lasting for at least 6 months according to clinical judgement and serum anti-PLA2R antibodies ≥50.0 RU/mL determined at screening by Euroimmun ELISA. 10. Cohort 2: Failure of immediate previous therapy, i.e. subject never achieved a complete immunological and/or clinical remission according to clinical judgement during or after completion of a recognized IST containing CSA, tacrolimus, MMF, ACTH or alkylating agents (e.g. cyclophosphamide), or RTX determined after at least 6 months after start of this IST. Serum anti-PLA2R antibodies ≥20.0 RU/mL measured at screening by the Euroimmun ELISA. 11. 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. 12. Female of non-childbearing potential fulfilling one of the criteria: a. post-menopausal: after 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) b. surgically sterile: tubal ligation at least 6 weeks before taking trial treatment, hysterectomy, or bilateral oophorectomy c. genetically sterile: e. g. Turner syndrome, uterine agenesis. 13. Sexually active females of reproductive potential should use one of the following contraception options until 3 months after the last dose of MOR202: a. One method of contraception that has a typical use failure rate of <1% (i.e., less than 1 pregnancy expected per 100 women), which would include sterilization surgery for women, sterilization implant for women, sterilization surgery for men, Copper IUD, IUD with progestin, or implantable rod b. A hormonal method of contraception (i.e., shot/injection, oral contraceptive, contraceptive patch, vaginal contraceptive ring, having typical use failure rate ≤ 9%) plus a barrier method (i.e., diaphragm with spermicide, sponge with spermicide, cervical cap with spermicide, male condom, female condom, spermicide alone).
Note: France will only enroll patients in Cohort 2.
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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) 8. Diabetes mellitus type 1 9. 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 membranous nephropathy without histological signs of diabetic nephropathy and their disease is controlled, such as: o Hba1c <8.0 % or 64 mmol/mol, o No diabetic retinopathy known o No peripheral neuropathy known 10. Previous treatment with an anti-CD38 antibody Note: Cohort 1 specific criteria are not applicable in France 11. Cohort 1a newly diagnosed subjects only: previous treatment with alkylating agents, RTX, cyclosporine, tacrolimus, MMF, all with or without corticosteroids 12. Cohort 1b relapse subjects and Cohort 2: Treatment within 3 months prior to screening with alkylating agents, RTX, CSA, tacrolimus, MMF, all with or without corticoster-oids 13. Significant uncontrolled cardiovascular disease or cardiac insufficiency (New York Heart Association [NYHA] class IV) as judged by the investigator 14. Clinically relevant findings on a 12 lead ECG as determined by the investigator at screening 15. History of significant cerebrovascular disease or sensory or motor neuropathy of tox-icity ≥ grade 3 16. Total bilirubin, aspartate aminotransferase and alanine aminotransferase >1.5 x ULN, alkaline phosphatase >2.0 x ULN 17. Treatment within five terminal half-lives (if known) or within the last 30 days prior to baseline (whatever is longer) with investigational drugs. 18. Known or suspected hypersensitivity to MOR202 and its excipients (L-histidine, su-crose, polysorbate 20) 19. Serologic or virologic markers positive for active or latent hepatitis B, C, or HIV at screening (central lab, HBsAg positive subjects are not eligible; HBcAb positive sub-jects are only eligible, if HBsAb is positive as well) 20. For any other preexisting symptoms and impairments of health classified or any re-sidual toxicity from prior therapy ≥ grade 3 (NCI-CTCAE, see 3.2): these subjects may be included upon confirmation by the medical department of the sponsor 21. Pregnancy or breast feeding
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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 | 5 |
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 |