E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
C3 glomerulopathy |
Glomerulopatía C3 |
|
E.1.1.1 | Medical condition in easily understood language |
Kidney disorder |
Trastorno renal |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• Cohort A: To evaluate the efficacy of LNP023 in reducing proteinuria at Week 12 • Cohort B: To assess histopathological changes in kidney biopsies at Week 12 |
- Cohorte A: Evaluar la eficacia de LNP023 en la disminución de la proteinuria en la semana 12 - Cohorte B: Evaluar cambios histopatológicos en las biopsias renales en la semana 12 |
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E.2.2 | Secondary objectives of the trial |
• All Cohorts: To assess the relationship between LNP023 dose and proteinuria • All Cohorts: To assess the effect of LNP023 on renal function • All Cohorts: To assess the effect of LNP023 on alternative complement pathway hyperactivity • All Cohorts: To assess the safety and tolerability of LNP023 • All Cohorts: To assess the plasma and urine pharmacokinetics of LNP023 in patients with C3G • Cohort B: To evaluate the efficacy of LNP023 in reducing proteinuria at Week 12 |
- Todas las cohortes: Evaluar la relación entre la dosis de LNP023 y la proteinuria. - Todas las cohortes: Evaluar el efecto de LNP023 en la función renal - Todas las cohortes: Evaluar el efecto de LNP023 en la hiperactividad de la vía alternativa del complemento - Todas las cohortes: Evaluar la seguridad y tolerabilidad de LNP023 - Todas las cohortes: Evaluar la farmacocinética en plasma y orina de LNP023 en pacientes con GC3 - Cohorte B: Evaluar la eficacia de LNP023 en la disminución de la proteinuria en la semana 12 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Cohort A and B: - Written informed consent must be obtained before any assessment is performed - Male and female patients between the ages of 18 to 65 (inclusive) at screening - C3G patients with proteinuria - Able to communicate well with the investigator, to understand and comply with the requirements of the study - At screening and baseline visits, patients must weigh at least 35 kg - Supine vital signs should be within the following ranges: oral body temperature between 35.0-37.5 °C systolic blood pressure, 80-170 mm Hg diastolic blood pressure, 50-105 mm Hg pulse rate, 45 - 100 bpm .
Cohort A: - Estimated GFR (using the CKD-EPI formula) or measured GFR ≥30mL/min per 1.73 m2 for patients on a maximum recommended or maximum tolerated dose of an angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) - UPCR ≥ 100 mg/mmol (equivalent to ≥ 1 g/24h total urinary protein excretion) - Prior to entry, all patients must have been on supportive care including a maximally tolerated dose of ACEi or ARB for at least 30 days.
Cohort B: - No histological/laboratory/clinical signs of allorejection - If applicable, induction treatment after allotransplantation needs to be completed >30 days before inclusion. - Transplantation of a kidney allograft >90 days before inclusion - Patients need to be on a stable dose of immunsuppressive regimen prior to inclusion. Any approved treatments are allowed for this purpose. |
Cohorte A y B: - Se tiene que obtener el consentimiento informado antes de realizar cualquier procedimiento - Los pacientes hombres y mujeres deberán tener entre 18 y 65 años(ambos inclusive) en la selección. - Pacientes con C3G con proteinuria - Ser capaces de comunicarse adecuadamente con el investigador, entender y cumplir con los requerimientos del estudio. - En las visitas de selección y basal, los patientes tienen que tener al menos 35kg de peso. - Los signos vitales en posición supina deben tener los siguientes rangos: temperatura oral del cuerpo entre 35.0-37.5ºC, prensión sanguinea sistólica 80-170 mm Hg y diastólica 50-105 mm Hg, pulso sanguineo 45 - 100 bpm. Cohorte A: - Tasa de filtración glomerular (TFG) estimada (utilizando la fórmula CKD-EPI) o TFG medida >=30 ml/min por 1.73 m2 para pacientes que reciban una dosis máxima recomendada o máxima tolerada de un inhibidor de la enzima convertidora de la angiotensina (IECA) o de antagonista del receptor de la angiotensina (ARA). - El índice proteína/creatinina en orina (UPCR) >= 100 mg/mmol (equivalente a excreción de proteína urinaria total >= 1 g/24h) . - Antes de entrar, todos los pacientes deberán haber mantenido dosis estables de cualquier medicación incluyendola dosis máxima tolerada de IECA o ARA durante por lo menos 30 días.
Cohorte B - Ningún signo histológico/ de laboratorio/ clinico de rechazo del aloinjerto - Si aplica, el tratamiento de inducción posterior al alotrasplante deberá haberse completado >30 días antes de la inclusión. - Trasplante de un aloinjerto de riñón >90 días antes de la inclusión - Los pacientes deberán haber mantenido una dosis estable del régimen inmunosupresor antes de la inclusión. Se permite cualquier tratamiento disponible comercialmente para este propósito |
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E.4 | Principal exclusion criteria |
Cohort A and B: - Use of other investigational drugs at the time of enrollment, or within 5 half-lives of randomization, or within 30 days, whichever is longer; or longer if required by local regulations - A history of clinically significant ECG abnormalities, - Known family history or known presence of long QT syndrome or Torsades de Pointes - Use of agents known to prolong the QT interval unless they can be permanently discontinued for the duration of the study - Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test. - Women of child bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 1 week after stopping of investigational drug. - History of immunodeficiency diseases, or a positive HIV (ELISA and Western blot) test result. - Chronic infection with Hepatitis B (HBV) or Hepatitis C (HCV). - Patients who cannot receive vaccinations against N. meningitidis, S. pneumoniae, or H. influenzae |
Cohorte A y B: - Uso de otros fármacos en investigación en el momento de la inclusión o dentro de 5 semividas de la aleatorización o dentro de los 30 días, lo que sea más largo; o más tiempo si lo requieren las regulaciones locales. - Antecedentes de ECG con anormalidades clinicamente significativas - Antecedentes familiares conocidos o presencia conocida de síndrome de QT prolongado o de Torsades de Pointes. - Uso de agentes conocidos para prolongar el intervalo dela QT a no ser que puedan ser interrumpidos durante la duración del estudio. - Mujeres embarazadas o en periodo de lactancia, donde el embarazo se define como el estado de una mujer después de la concepción y hasta el final de la gestación, confirmado con una prueba de laboratorio hCG positiva. - Mujeres fertiles, definidas como todas las mujeres fisiologicamente capaces de quedarse embarazadas, a no ser que usen metodos anticonceptivos altamente eficaces durante el tratamiento y hasta una semana despues de para el medicamento en investigación. - Antecedentes de enfermedad inmunodeficiente, o test de VIH positivo (ELISA y Western blot) - Infección crónica con Hepatitis B (VHB) o Hepatitis C (VHC) - Pacientes que no puedan recibir vacunas contra N. meningitidis, S. pneumoniae o H. influenzae. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Cohort A: Change from baseline in UPCR Cohort B: Change from baseline in C3 Deposit |
Cohorte A: Cambio, respecto a la visita basal, en el UPCR Cohorte B: Cambio, respecto a la visita basal, en la puntuación del depósito C3 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
PD variables Pharmacokinetics variables Biomarker C3 Biomarker Bb |
Variables FD Variables Farmacocinéticas Biomarcadores C3 Biomarcadores Bb |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
PD variables Week 12 Pharmacokinetics variables Week 1, 2, 3, 4, 13, 14 Biomarker C3 Week 1,2, 3, 4, and 12 Biomarker Bb Week 1, 2, 3, 4 and 12 |
Variables FD semana 12 Variables Farmacocinéticas semanas 1, 2, 3, 4, 13, 14 Biomarcadores C3 semanas 1,2, 3, 4, y 12 Biomarcadores Bb semanas 1,2, 3, 4, y 12 |
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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 | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
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 | 3 |
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 | 12 |
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 |
France |
Germany |
Italy |
Spain |
United Kingdom |
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
|
LVLS |
Ultima visita del ultimo sujeto |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |