E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary (anti-PLA2R antibody positive) Membranous Nephropathy |
Primario (anticuerpo anti-PLA2R positivo) membranosa nefropatía |
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E.1.1.1 | Medical condition in easily understood language |
Membranous Nephropathy (a condition of the kidneys). |
Nefropatía membranosa (una condición de los riñones). |
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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) |
Evaluar la seguridad y la tolerabilidad del tratamiento con MOR202 en sujetos con nefropatía membranosa positiva al anticuerpo anti-PLA2R (aMN) |
|
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 |
Evaluar el efecto de MOR202 sobre los anticuerpos séricos anti-PLA2R en sujetos con NM Para evaluar la inmunogenicidad de MOR202 (formación de anticuerpos anti-MOR202) Para evaluar el perfil farmacocinético (FC) de MOR202 Evaluar la seguridad en la fase de seguimiento. |
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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. |
1. ≥18 a ≤80 años de edad (en la fecha de la firma del FCI). 2. Cociente proteína/creatinina (P/C) en orina de ≥3,0 g/g (medido a partir de una recogida de orina de 24 horas). 3. NM diagnosticada en base a una biopsia; se acepta una biopsia de archivo obtenida en los 5 años previos a la selección. 4. Tasa de filtración glomerular estimada (TFGe) ≥50 ml/min/1,73 m² o >30 y <50 ml/min/1,73 m², y una puntua-ción FIAT (fibrosis intersticial y atrofia tubular) de menos del 25 % en una biopsia renal obtenida en los 6 meses anteriores al inicio de la selección. Si un sujeto se encuentra en este último intervalo sin disponibilidad de una biopsia adecuada, se deberá realizar una biopsia en la selección para la evaluación FIAT. 5. El sujeto recibe tratamiento de apoyo con un IECA o un BRA durante al menos 4 semanas antes de la selección. El tratamiento con IECA o BRA debe haber alcanzado una dosis estable según la mejor práctica local. 6. TA sistólica ≤150 mmHg y TA diastólica ≤100 mmHg tras un periodo de 5 minutos de reposo, según la medición realizada en la selección. 7. Paciente vacunado contra neumococo en los 3 años previos a la fecha de la firma del FCI (los sujetos pueden ser vacunados du-rante la selección para cumplir este criterio; el intervalo de tiem-po hasta la primera dosis de MOR202 debe ser de al menos 14 días) (1). 8. Cohorte 1: Anticuerpos anti-PLA2R en suero ≥150,0 UR/ml se-gún lo determinado en la selección mediante Euroimmun ELI-SA. 9. Cohorte 1: Anticuerpos anti-PLA2R en suero antes de la selec-ción en aumento o estables, según el criterio del investigador. 10. Cohorte 1, solo sujetos en recidiva: Debe haber tenido una remi-sión completa de la proteinuria o una combinación de remisión parcial de la proteinuria (que demuestre por lo menos una reduc-ción del 50 %) con una remisión del título de anticuerpos anti-PLA2R en suero a menos de 20,0 UR/ml (Euroimmun ELISA) o un resultado negativo de la prueba de inmunofluorescencia (PIF). La remisión debe haber durado al menos 6 meses de conformidad con el juicio clínico. 11. Cohorte 2: Fracaso del tratamiento anterior, es decir, el sujeto nunca logró una reducción de los títulos de anticuerpos anti-PLA2R en suero por debajo de 20,0 UR/ml (Euroimmun ELISA) durante o después de la finalización de un TID reconocido que contuviera CSA, tacrolimús, MMF, ACTH o agentes alquilantes (p. ej., ciclofosfamida) o RTX, según se determinó después de al menos 6 meses desde del inicio de este TID. 12. Cohorte 2: Los sujetos pueden haber recibido un máximo de dos líneas de tratamiento previas de tratamiento inmunodepresor (la repetición del tratamiento para la recidiva con la misma pauta se considera una línea de tratamiento). Una secuencia fija y planifi-cada de distintos agentes terapéuticos (p. ej., pauta STAR-MEN)(2) se considera como una pauta. |
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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) |
1. Hemoglobina <90 g/l 2. Trombocitopenia: Plaquetas <100,0 × 109/l 3. Neutropenia: Neutrófilos <1,5 x 109/l 4. Leucopenia: Leucocitos <3,0 x 109/l 5. Hipogammaglobulinemia: Inmunoglobulinas séricas ≤5,0 g/l 6. Causa secundaria de NM (p. ej., LES, medicamentos, neoplasias malignas) según lo determinado por el investigador 7. Enfermedad renal concomitante, aparte de NM (p. ej., enfermedad renal diabética, nefritis lúpica, nefropatía por IgA) |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Incidence and severity of treatment-emergent adverse events (TEAE) |
Incidencia e intensidad de los acontecimientos adversos surgidos durante el tratamiento (AAST) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Throughout the study |
A lo largo del estudio |
|
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 |
CRITERIO DE VALORACIÓN SECUNDARIO CLAVE: Mejor respuesta inmunológica: tasa de RCIs, RCI y RPI en base a la reducción del título de anticuerpos anti-PLA2R en suero CRITERIOS DE VALORACIÓN SECUNDARIOS: 1. Número y títulos de anticuerpos de los sujetos que dieron positivo para anticuerpos anti-MOR202 2. Concentraciones séricas de MOR202 después de múltiples administraciones por vía i.v. 3. Incidencia e intensidad de las reacciones adversas al fármaco (RAF) en la fase de seguimiento. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Throughout the study |
A lo largo del estudio |
|
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 |
Immunogenicity |
Inmunogenicidad |
|
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 |
|
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 | 3 |
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 |
|
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
|
LVLS |
Ultima visita del último sujeto20 |
|
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 |