E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 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 |
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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 |
Determine the efficacy of ALXN1830 compared to placebo in adult subjects with WAIHA |
Determinar la eficacia de ALXN1830 en comparación con el placebo en sujetos adultos con AHAIC |
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E.2.2 | Secondary objectives of the trial |
- Assess the effect of ALXN1830 on the need for transfusions compared to placebo - Assess the effect of ALXN1830 on quality of life compared to placebo - Assess the effect on ALXN1830 on anemia compared to placebo - Assess the effect of ALXN1830 on hemolysis compared to placebo - Assess the effect of ALXN1830 on corticosteroid usage compared to placebo - Assess the safety and tolerability of ALXN1830 compared to placebo - Assess the effect of ALXN1830 on serum total IgG levels compared to placebo |
- Evaluar el efecto de ALXN1830 sobre la necesidad de transfusiones en comparación con el placebo - Evaluar el efecto de ALXN1830 sobre la calidad de vida en comparación con el placebo - Evaluar el efecto de ALXN1830 sobre la anemia en comparación con el placebo - Evaluar el efecto de ALXN1830 sobre la hemólisis en comparación con el placebo - Evaluar el efecto de ALXN1830 sobre el uso de corticoesteroides en comparación con el placebo - Evaluar la seguridad y tolerabilidad de ALXN1830 en comparación con el placebo - Evaluar el efecto de ALXN1830 sobre los niveles de IgG total en suero en comparación con el placebo |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject must be at least 18 years of age at the time of signing the informed consent 2. Primary or secondary WAIHA, diagnosed 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 6. Positive direct antiglobulin test (Coombs) (IgG positive who are positive or negative for the presence of complement C3 [C3]) at Screening 7. Evidence of active hemolysis including any one of the below: a. LDH > upper limit of normal (ULN) or b. Haptoglobin < lower limit of normal (LLN) or c. Indirect bilirubin > ULN 8. Total IgG > 500 mg/dL at Screening |
1. El sujeto debe tener al menos 18 años de edad en el momento de la firma del consentimiento informado 2. AHAIC primaria o secundaria, diagnosticada al menos 6 semanas antes de la selección 3. Haber fracasado o no haber tolerado al menos una pauta de tratamiento anterior para la AHAIC, por ejemplo, corticoesteroides, rituximab, azatioprina, ciclofosfamida, ciclosporina, micofenolato de mofetilo, danazol o vincristina 4. Hemoglobina <10 g/dl y ≥6 g/dl 6. Resultado positivo en la prueba de antiglobulina directa (prueba de Coombs) (IgG positivas con o sin presencia del complemento C3 [C3]) en la selección 7. Indicios de hemólisis activa, incluidos cualquiera de los siguientes: a. LDH > límite superior de la normalidad (LSN) o b. Haptoglobina < límite inferior de la normalidad (LIN) o c. Bilirrubina indirecta > LSN 8. IgG total >500 mg/dl en la selección |
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E.4 | Principal exclusion criteria |
1. Packed RBC or whole blood transfusions in the 2 weeks prior to Screening 2. History of cold antibody 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. History of leukemia, Hodgkin, or non-Hodgkin lymphoma. Exception: low-grade chronic lymphocytic leukemia (CLL) with no enlargement of lymph nodes, spleen, or liver, and normal platelet count as per central lab, not requiring treatment for CLL, no more than 3 years since the diagnosis of CLL and after discussion with the Sponsor’s Medical Monitor. 6. 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 subject had not been disease-free for at least 5 years 7. Active infection or history of recurrent systemic infections in the 2 years prior to Screening 9. Systemic lupus erythematosus (SLE) or other autoimmune disease that is not stable or not well controlled on current therapy |
1. Transfusiones de concentrado de eritrocitos o sangre completa en las 2 semanas anteriores a la selección 2. Antecedentes de AHAI por anticuerpos fríos, síndrome de aglutininas frías, AHAI de tipo mixto o hemoglobinuria paroxística por frío 3. Antecedentes de anemia hemolítica autoinmunitaria inducida por fármacos o relacionada con infección 4. Deficiencia de hierro, ácido fólico o vitamina B12 5. Antecedentes de leucemia o de linfoma de Hodgkin o no Hodgkin. Excepción: leucemia linfocítica crónica (LLC) de bajo grado sin engrosamiento de los ganglios linfáticos, el bazo o el hígado, y con un recuento de plaquetas normal según el laboratorio central; no requiere tratamiento para la LLC; no han transcurrido más de 3 años desde el diagnóstico de LLC; y después de consultarlo con el supervisor médico del promotor. 6. Antecedentes de neoplasia maligna sólida distinta al carcinoma basocelular o espinocelular de la piel, carcinoma de cuello uterino in situ u otra neoplasia maligna de la que el sujeto no haya estado libre durante al menos 5 años 7. Infección activa o antecedentes de infecciones sistémicas recurrentes en los 2 años anteriores a la selección 9. Lupus eritematoso sistémico (LES) u otra enfermedad autoinmunitaria que no sea estable o no esté bien controlada con el tratamiento actual |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects achieving a ≥ 2 g/dL increase in Hgb, without requiring increase in any WAIHA medication after Day 1 and without pRBC transfusions after Day 14. |
Proporción de sujetos que logran un aumento ≥2 g/dl en la Hgb, sin necesidad de aumentar ninguna medicación para la AHAIC después del día 1 y sin transfusiones de concentrado de eritrocitos (CE) después del día 14. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline (Day 1) to Day 92 (after 13 weeks of treatment) |
Desde el inicio (día 1) hasta el día 92 (después de 13 semanas de tratamiento) |
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E.5.2 | Secondary end point(s) |
- Total number of units of pRBCs transfused from Day 15 to Day 92 - Change in quality of life (QoL) assessed via EQ-5D-5L and Functional Assessment of Cancer Therapy Anemia (FACT-AN) from baseline to Day 92 - Durability: number of weekly Hgb measurements ≥ 2 g/dL over baseline - Proportion of subjects who require new WAIHA rescue medication or increase in the dose of an existing WAIHA medication or pRBC transfusions (Day 15 to Day 92) for the treatment of anemia - Markers of hemolysis: absolute and percentage change from baseline to Day 92 in serum lactate dehydrogenase (LDH) levels, absolute reticulocyte count, serum indirect bilirubin, serum haptoglobin - Total corticosteroid use from Day 1 to Day 92 - Safety and tolerability of ALXN1830 compared to placebo assessed by physical examinations, vital signs, ECGs, laboratory assessments, and incidence of AEs, SAEs and AESIs - Serum concentration of ALXN1830 over time - Mean and percentage decrease in serum total IgG levels by dose group (ALXN1830 vs placebo) and time point |
- Número total de unidades de CE transfundidas desde el día 15 hasta el día 92 - Cambio en la calidad de vida (CdV) evaluada mediante el EQ-5D-5L y la evaluación funcional del tratamiento contra el cáncer-anemia (Functional Assessment of Cancer Therapy Anemia, FACT-AN) desde el inicio hasta el día 92 - Durabilidad: número de mediciones semanales de Hgb ≥2 g/dl con respecto al inicio - Proporción de sujetos que necesitan una nueva medicación de rescate para la AHAIC, un aumento en la dosis de un medicamento ya existente para la AHAIC o transfusiones de CE (desde el día 15 hasta el día 92) para el tratamiento de la anemia - Marcadores de hemólisis: cambio absoluto y porcentual desde el inicio hasta el día 92 en los niveles séricos de lactato deshidrogenasa (LDH), recuento absoluto de reticulocitos, bilirrubina indirecta en suero, haptoglobina en suero - Uso total de corticoesteroides desde el día 1 hasta el día 92 - Seguridad y tolerabilidad de ALXN1830 en comparación con el placebo evaluadas mediante exploraciones físicas, constantes vitales, ECG, pruebas analíticas e incidencia de AA, AAG y AAEI - Concentración sérica de ALXN1830 a lo largo del tiempo - Disminución media y porcentual de los niveles de IgG total en suero por grupo de dosis (ALXN1830 frente a placebo) y punto temporal |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The timepoint(s) is precised for each secondary end point at E.5.2 |
Los puntos temporales para cada criterio de valoración secundario se detallan en E.5.2 |
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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 | 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 | 4 |
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 | 38 |
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 |
Australia |
Belgium |
Canada |
France |
Germany |
Italy |
Korea, Republic of |
Netherlands |
Russian Federation |
Spain |
Taiwan |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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LVLS |
Última visita del último paciente |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | |
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 | 6 |