E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Warm Autoimmune Hemolytic Anemia (WAIHA) |
Anemia hemolítica autoinmunitaria por anticuerpos calientes |
|
E.1.1.1 | Medical condition in easily understood language |
Autoimmune disorder characterized by the premature destruction of healthy red blood cells |
Trastorno autoinmunitario caracterizado por la destrucción prematura de eritrocitos sanos |
|
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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003825 |
E.1.2 | Term | Autoimmune hemolytic anemia |
E.1.2 | System Organ Class | 100000004851 |
|
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 |
Determine the efficacy of ALXN1830 compared to placebo in the treatment of WAIHA |
Determinar la eficacia de ALXN1830 en comparación con placebo en el tratamiento de la WAIHA. |
|
E.2.2 | Secondary objectives of the trial |
1. Assess the effect of ALXN1830 on the need for transfusions compared to placebo 2. Assess the effect on ALXN1830 on anemia compared to placebo 3. Evaluate the efficacy of ALXN1830 after 4 weeks compared to placebo 4. Assess the effect on ALXN1830 on hemolysis compared to placebo 5. Assess the effect of ALXN1830 on corticosteroid usage compared to placebo 6. Assess the safety and tolerability of ALXN1830 compared to placebo 7. Assess the immunogenicity of ALXN1830 compared to placebo 8. Assess the pharmacokinetics (PK) of ALXN1830 9. Assess the effect of ALXN1830 on serum total IgG levels compared to placebo 10. Assess the effect of ALXN1830 on other PD biomarkers compared to placebo |
1.Evaluar el efecto de ALXN1830 en comparación con placebo sobre la necesidad de transfusiones de sangre. 2. Evaluar el efecto de ALXN1830 en comparación con placebo sobre la anemia. 3. Evaluar la eficacia de ALXN1830 en comparación con placebo después de 4 semanas. 4. Evaluar el efecto de ALXN1830 en comparación con placebo sobre la hemolisis. 5. Evaluar el efecto de ALXN1830 en comparación con placebo sobre el uso de corticosteroides. 6. Evaluar la seguridad y la tolerabilidad de ALXN1830 en comparación con el placebo. 7. Evaluar la inmunogenicidad de ALXN1830 en comparación con el placebo. 8. Evaluar la farmacocinética (FC) de ALXN1830. 9. Evaluar el efecto de ALXN1830 sobre las concentraciones séricas de IgG total en comparación con placebo. 10. Evaluar el efecto de ALXN1830 sobre otros biomarcadores FD en comparación con placebo. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Participant must be at least 18 years of age inclusive, at the time of signing the informed consent 2. Diagnosed with primary or secondary WAIHA at least 6 weeks prior to Screening 3. Failed or have not tolerated at least one prior WAIHA treatment regimen, for example, corticosteroids, rituximab, azathioprine, cyclophosphamide, cyclosporine, mycophenolate mofetil, danazol, or vincristine 4. Hemoglobin < 10 g/dL and ≥ 6 g/dL at Screening 5. Positive direct antiglobulin test (Coombs) (IgG positive who are positive or negative for the presence of complement C3 [C3]) at Screening 6. Evidence of active hemolysis |
1. El participante debe tener 18 años o más en el momento de firmar el consentimiento informado. 2. Diagnóstico de WAIHA primaria o secundaria al menos 6 semanas antes de la selección 3. Fracaso o intolerancia al menos a una pauta de tratamiento previa de la WAIHA; por ejemplo, corticosteroides, rituximab, azatioprina, ciclofosfamida, ciclosporina, micofenolato mofetilo, danazol o vincristina 4. Hemoglobina <10 g/dl y ≥6 g/dl en la selección 5. Prueba de antiglobulina directa (Coombs) positiva (IgG positiva que sea positiva o negativa para la presencia del complemento C3 [C3]) en la selección 6. Signos de hemólisis activa |
|
E.4 | Principal exclusion criteria |
1. Packed RBC or whole blood transfusions in the 2 weeks prior to Screening 2. History of cold antibody autoimmune hemolytic anemia (AIHA), cold agglutinin syndrome, mixed type AIHA, or paroxysmal cold hemoglobinuria 3. History of drug-induced or infection-related immune hemolytic anemia 4. Iron, folic acid, or vitamin B12 deficiency 5. Participants with Evan’s syndrome 6. History of leukemia, Hodgkin, or non Hodgkin lymphoma 7. History of solid malignancy other than basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or other malignancy for which the participant had not been disease free for at least 5 years 8. Active infection or history of recurrent systemic infections in the 2 years prior to Screening 10. Systemic lupus erythematosus (SLE) or other autoimmune disease that is not stable or not well controlled on current therapy |
1. Transfusiones de concentrados de eritrocitos o de sangre completa en las 2 semanas previas a la selección 2. Antecedentes de anemia hemolítica autoinmunitaria (AIHA) por anticuerpos por frío, síndrome de aglutinina por frío, AIHA de tipo mixto o hemoglobinuria paroxística por frío 3. Antecedentes de anemia hemolítica inmunitaria inducida por fármacos o relacionada con infecciones 4. Deficiencia de hierro, ácido fólico o vitamina B12 5. Participantes con síndrome de Evan 6. Antecedentes de leucemia, linfoma de Hodgkin o linfoma no hodgkiniano. 7. Antecedentes de neoplasia maligna sólida distinta del carcinoma basocelular o espinocelular de la piel, carcinoma in situ de cuello uterino u otra neoplasia maligna por cuya causa el participante no haya estado libre de enfermedad durante al menos 5 años 8. Infección activa o antecedentes de infecciones sistémicas recurrentes en los 2 años previos a la selección 10. Lupus eritematoso sistémico (LES) u otra enfermedad autoinmunitaria que no se mantenga estable o no esté bien controlada con el tratamiento actual |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of participants achieving a ≥ 2 g/dL increase in Hgb from Baseline (Day 1) to the end of Primary Treatment, without requiring any increase in the dose of an existing WAIHA medication after Day 1 and without pRBC transfusions after Day 14 |
Proporción de participantes que experimenten un aumento ≥2 g/dl de la Hb entre el momento basal (día 1) y el final del tratamiento principal, sin necesidad de aumentar la dosis de una medicación existente para la WAIHA después del día 1 y sin transfusiones de concentrado de eritrocitos después del día 14. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
End of Primary Treatment (Day 57 or Day 85) |
Final del tratamiento principal (día 57 o día 85) |
|
E.5.2 | Secondary end point(s) |
1. Total number of units of pRBCs transfused: 2. Durability: number of Hgb measurements ≥ 2 g/dL 4. Proportion of participants who require new WAIHA rescue medication or any increase in the dose of an existing WAIHA medication or pRBC transfusions for the treatment of anemia 5. Proportion of participants achieving a ≥ 2 g/dL increase in Hgb, without requiring any increase in the dose of an existing WAIHA medication 6. Markers of hemolysis: absolute and percentage change in serum lactate dehydrogenase (LDH) levels, absolute reticulocyte count, serum indirect bilirubin, and serum haptoglobin 7. Total corticosteroid usage from Baseline (Day 1) to the end of Primary Treatment 13. Incidence of AEs, SAEs and AESIs over time 15. Serum concentrations of ALXN1830 over time 16. Serum total IgG levels |
1. Número total de unidades de concentrado de eritrocitos transfundidas. 2. Durabilidad: número de mediciones de Hb ≥2 g/dl. 4. Proporción de participantes que necesitan nueva medicación de rescate para la WAIHA o cualquier aumento de la dosis de una medicación existente para la WAIHA o transfusiones de concentrado de eritrocitos para el tratamiento de la anemia. 5. Proporción de participantes que experimenten un aumento ≥2 g/dl de la Hb sin necesidad de aumentar la dosis de una medicación existente para la WAIHA. 6. Marcadores de hemolisis: cambio absoluto y porcentual de la concentración sérica de lactato deshidrogenasa (LDH), el recuento absoluto de reticulocitos, la bilirrubina indirecta sérica y la haptoglobina sérica. 7. Uso total de corticosteroides desde el momento basal (día 1) hasta el final del tratamiento principal. 13. Incidencia de AA, AAG y AAIE a lo largo del tiempo. 15. Concentraciones séricas de ALXN1830 a lo largo del tiempo. 16. Concentraciones séricas de IgG total. |
|
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 | Yes |
E.6.10 | Pharmacogenetic | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 |
Korea, Republic of |
United States |
France |
Germany |
Italy |
Spain |
United Kingdom |
|
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
|
Date when the last participant completes the last visit (including follow-up) |
Fecha en la que el último participante complete la última vista (incluido el seguimiento) |
|
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 | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |