E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Paroxysmal Nocturnal Hemoglobinuria (PNH) |
Hemoglobinuria paroxística nocturna (HPN) |
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E.1.1.1 | Medical condition in easily understood language |
Paroxysmal Nocturnal Hemoglobinuria (PNH) |
Hemoglobinuria paroxística nocturna (HPN) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10034042 |
E.1.2 | Term | Paroxysmal nocturnal haemoglobinuria |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
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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 |
To evaluate the efficacy of ALXN2050 based on improvement in hemoglobin (Hgb) |
Evaluar la eficacia de ALXN2050 en función de la mejora de la hemoglobina (Hgb) |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of ALXN2050 based on reduction in transfusion requirements • To evaluate the efficacy of ALXN2050 based on lactate dehydrogenase (LDH) • To assess laboratory markers of hemolysis and other markers relevant in patients with paroxysmal nocturnal hemoglobinuria (PNH) |
• Evaluar la eficacia de ALXN2050 en función de la reducción de las necesidades de transfusión • Evaluar la eficacia de ALXN2050 en función de la lactato deshidrogenasa (LDH) • Evaluar los marcadores analíticos de hemólisis y otros marcadores relevantes en pacientes con hemoglobinuria paroxística nocturna (HPN) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All patients must meet all of the following conditions: 1. Diagnosis of PNH. 2. Male or female, ≥ 18 years of age (or minimum adult age in accordance with local legal requirements).
Eligibility Criteria Specific for Group 1: 1. PNH Patients who have no history of treatment with any complement inhibitor at any dose. 2. PNH Type III erythrocyte or granulocyte clone size ≥10% 3. Absolute reticulocyte count ≥100×10^9/liter [L]. 4. Anemia (Hgb <10.5 grams/deciliter [g/dL]). 5. LDH ≥1.5× upper limit of normal. 6. Platelet count ≥30,000/microliter (µL) without the need for platelet transfusions. 7. Absolute neutrophil count (ANC) ≥750/ µL.
Eligibility Criteria Specific for Group 2: Patients on stable eculizumab switching to ALXN2050 (Group 2) must meet the following criteria: 1. Stable background regimen of at least 24 weeks for eculizumab without change in dose or interval for at least the past 8 weeks 2. Anemia (Hgb <10 g/dL) 3. Absolute reticulocyte count ≥100×10^9/L 4. Platelet count ≥30,000/µL without the need for platelet transfusions 5. Absolute neurophil count (ANC) ≥750/ µL
Eligibility Criteria Specific for Group 3: 1. Patient received danicopan during Study ACH-471-103. |
Todos los pacientes deben cumplir todas las condiciones siguientes: 1. Diagnóstico de HPN. 2. Hombre o mujer, ≥18 años de edad (o edad adulta mínima de acuerdo con los requisitos legales locales). Criterios de elegibilidad específicos para el grupo 1: 1. Pacientes con HPN que no tienen antecedentes de tratamiento con ningún inhibidor del complemento a ninguna dosis. 2. Tamaño del clon de granulocitos o eritrocitos tipo III de HPN ≥10 % 3. Recuento absoluto de reticulocitos ≥100×10^9/litro [l]. 4. Anemia (Hgb <10,5 gramos/decilitro [g/dl]). 5. ≥1,5 x LSN (límite superior de la normalidad). 6. Recuento plaquetario ≥30 000/microlitro (μl) sin necesidad de transfusiones de plaquetas. 7. Cifra absoluta de neutrófilos (ANC) ≥750/μL.
Criterios de elegibilidad específicos para el grupo 2: Los pacientes con eculizumab estable que cambien a ALXN2050 (grupo 2) deben cumplir los siguientes criterios: 1. Régimen de base estable de al menos 24 semanas para eculizumab sin cambio en la dosis o el intervalo durante al menos las últimas 8 semanas 2. Anemia (Hgb <10 g/dl) 3. Recuento absoluto de reticulocitos ≥100×10^9/l 4. Recuento plaquetario ≥30 000/μl sin necesidad de transfusiones de plaquetas 5. Cifra absoluta de neutrófilos (ANC) ≥750/ μL Criterios de elegibilidad específicos para el grupo 3: 1. El paciente recibió danicopán durante el estudio ACH-471-103. |
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E.4 | Principal exclusion criteria |
1. History of a major organ transplant or hematopoietic stem cell/marrow transplant . 2. Known aplastic anemia or other bone marrow failure that requires HSCT, or if these patients are on immunosuppressive agents such as (but not limited to) cyclosporine, tacrolimus, mycophenolate, or others for less than 24 weeks prior to enrollment. 3. Known underlying bleeding disorders (eg, coagulation factor deficiencies, idiopathic thrombocytopenic purpura, Von Willebrand disease) or any other conditions leading to anemia not primarily associated with PNH. 4. Estimated glomerular filtration rate <30 milliliters/minute/1.73 meters squared and/or are on dialysis. |
1. Antecedentes de trasplante de órganos importantes o trasplante de células madre hematopoyéticas/médula ósea. 2. Anemia aplásica conocida u otra insuficiencia de la médula ósea que requiera TCMH, o si estos pacientes están recibiendo inmunodepresores como (entre otros) ciclosporina, tacrolimus, micofenolato u otros durante menos de 24 semanas antes de la inscripción. 3. Trastornos hemorrágicos subyacentes conocidos (p. ej., deficiencias del factor de coagulación, púrpura trombocitopénica idiopática, enfermedad de Von Willebrand) o cualquier otra afección que lleve a anemia no asociada principalmente a la HPN. 4. Tasa de filtración glomerular estimada <30 mililitros/minuto/1,73 metros cuadrados y/o están en diálisis. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Change in Hgb relative to baseline |
1. Cambio en la Hgb en relación con el valor inicial |
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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) |
2. Number Of Patients Who Have Transfusion Avoidance 3. Number Of RBC Units Transfused and Transfusion Instances Transfusion requirements during the 12 weeks of treatment will be compared to 12 weeks of historical transfusion requirements. 4. Change In LDH Relative to Baseline 5. Change From Baseline In Absolute Reticulocyte Count 6. Change From Baseline In Direct Bilirubin 7. Change From Baseline In Total Bilirubin 8. Change From Baseline In PNH RBC Clone Size 9. Change From Baseline In C3 Complement Protein Fragment Deposition On PNH RBCs 10. Incidence of TEAEs, SAEs, and Events Leading To Discontinuation Of Study Medication 11. Change in HgB Relative To Baseline 12. Change in LDH Relative To Baseline 13. Change in FACIT Fatigue Scale (Version 4) Scores Relative To Baseline |
2. Número de pacientes con ahorro de transfusiones 3. Número de unidades de eritrocitos Transfundidas e Instancias de transfusión Las necesidades de transfusión durante las 12 semanas de tratamiento se compararán con las 12 semanas de necesidades de transfusión históricas. 4. Cambio en la LDH con respecto al inicio 5. Cambio desde el inicio en el recuento absoluto de reticulocitos 6. Cambio desde el inicio en la bilirrubina directa 7. Cambio con respecto al inicio en la bilirrubina total 8. Cambio desde el inicio en el tamaño del clon de eritrocitos de HPN 9. Cambio desde el inicio en el fragmento de proteína del complemento C3 Depósito en los eritrocitos de HPN 10. Incidencia de AAST, AAG y acontecimientos que provocaron la interrupción del medicamento del estudio 11. Cambio en HgB con respecto al inicio 12. Cambio en la LDH con respecto al inicio 13. Cambio en las puntuaciones de la escala de fatiga FACIT (versión 4) en relación con el inicio |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
2 - 3: Up to Week 12 4 - 9: Week 12 10: Through Study Completion, An Average Of 121 Weeks 11 - 12: Long-term Extension Period, Week 16 to Week 108 13: Week 12, Week 108 |
2 - 3: Hasta la semana 12 4 - 9: Semana 12 10: Hasta la finalización del estudio, una media de 121 semanas 11 - 12: Período de extensión a largo plazo, de la semana 16 a la semana 108 13: Semana 12, Semana 108 |
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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 | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Effect on biomarkers |
Efecto en los biomarcadores |
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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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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 |
Canada |
Korea, Republic of |
New Zealand |
Turkey |
France |
Germany |
Italy |
Spain |
United Kingdom |
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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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The end of the study is defined as the date of the last visit of the last patient remaining in the study. |
El final del estudio se define como la fecha de la última visita del último paciente que queda en el estudio. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |