E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Warm Autoimmune Hemolytic Anemia (WAIHA) |
Anemia emolitica autoimmune calda (WAIHA) |
|
E.1.1.1 | Medical condition in easily understood language |
Autoimmune disorder characterized by the premature destruction of healthy red blood cells |
Disturbo autoimmune caratterizzato dalla distruzione prematura dei globuli rossi sani |
|
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 |
Determinare l'efficacia di ALXN1830 rispetto al placebo nel trattamento di 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. Valutare l'effetto di ALXN1830 sulla necessità di trasfusioni rispetto al placebo 2. Valutare l'effetto di ALXN1830 sull'anemia rispetto al placebo 3. Valutare l'efficacia di ALXN1830 dopo 4 settimane rispetto al placebo 4. Valutare l'effetto di ALXN1830 sull'emolisi rispetto al placebo 5. Valutare l'effetto di ALXN1830 sull'uso di corticosteroidi rispetto al placebo 6. Valutare la sicurezza e la tollerabilità di ALXN1830 rispetto al placebo 7. Valutare l'immunogenicità di ALXN1830 rispetto al placebo 8. Valutare la farmacocinetica (PK) di ALXN1830 9. Valutare l'effetto di ALXN1830 sui livelli sierici di IgG totali rispetto al placebo 10. Valutare l'effetto di ALXN1830 su altri biomarcatori PD rispetto al 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. Il partecipante deve avere almeno 18 anni compresi, al momento della firma del consenso informato 2. Diagnosticato con WAIHA primario o secondario almeno 6 settimane prima dello screening 3. Ha fallito o non ha tollerato almeno un precedente regime di trattamento WAIHA, ad esempio corticosteroidi, rituximab, azatioprina, ciclofosfamide, ciclosporina, micofenolato mofetile, danazolo o vincristina 4. Emoglobina < 10 g/dL e = 6 g/dL allo Screening 5. Positivo al test dell'antiglobulina diretto (Coombs) (IgG positivi che sono positivi o negativi per la presenza del complemento C3 [C3]) allo Screening 6. Evidenza di emolisi attiva |
|
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. Trasfusioni di globuli rossi o sangue intero nelle 2 settimane precedenti lo screening 2. Storia di anemia emolitica autoimmune da anticorpi freddi (AIHA), sindrome da agglutinine fredde, AIHA di tipo misto o emoglobinuria parossistica fredda 3. Storia di anemia emolitica immunitaria indotta da farmaci o correlata all'infezione 4. Carenza di ferro, acido folico o vitamina B12 5. Partecipanti con la sindrome di Evan 6. Storia di leucemia, linfoma di Hodgkin o non Hodgkin 7. Storia di tumore solido diverso da carcinoma basocellulare o a cellule squamose della pelle, carcinoma in situ della cervice o altri tumori per i quali il partecipante non era libero da malattia da almeno 5 anni 8. Infezione attiva o storia di infezioni sistemiche ricorrenti nei 2 anni precedenti lo Screening 10. Lupus eritematoso sistemico (LES) o altra malattia autoimmune che non è stabile o non ben controllata con la terapia attuale |
|
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 |
Percentuale di partecipanti che hanno ottenuto un aumento di = 2 g/dL di Hgb dal basale (giorno 1) alla fine del trattamento primario, senza richiedere alcun aumento della dose di un farmaco WAIHA esistente dopo il giorno 1 e senza trasfusioni di globuli rossi dopo il giorno 14 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
End of Primary Treatment (Day 57 or Day 85) |
Fine del trattamento primario (giorno 57 o giorno 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. Numero totale di unità di PRBC trasfuse: 2. Durabilità: numero di misurazioni di Hgb = 2 g/dL 4. Percentuale di partecipanti che richiedono nuovi farmaci di salvataggio WAIHA o qualsiasi aumento della dose di un farmaco WAIHA esistente o pRBC trasfusioni per il trattamento dell'anemia 5. Percentuale di partecipanti che ottengono un aumento di Hgb = 2 g/dL, senza richiedere alcun aumento della dose di un farmaco WAIHA esistente 6. Marcatori di emolisi: variazione assoluta e percentuale dei livelli sierici di lattato deidrogenasi (LDH), conta assoluta dei reticolociti, siero bilirubina indiretta e aptoglobina sierica 7. Utilizzo totale di corticosteroidi dal basale (giorno 1) alla fine del trattamento primario 13. Incidenza di AE, SAE e AESI nel tempo 15. Concentrazioni sieriche di ALXN1830 nel tempo 16. Livelli sierici totali di IgG |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Throughout the study |
Durante lo studio |
|
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 | Information not present in EudraCT |
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) |
Data in cui l'ultimo partecipante completa l'ultima visita (incluso il follow-up) |
|
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 |