E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
warm autoimmune hemolytic anemia |
anemia emolitica autoimmune calda |
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E.1.1.1 | Medical condition in easily understood language |
warm autoimmune hemolytic anemia |
anemia emolitica autoimmune calda |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this repeat dose Phase 2 study is as follows: • To evaluate the safety, tolerability, and proof of concept of two once-weekly intravenous infusions of 100 mg/kg ANX005 in subjects with wAIHA. |
L'obiettivo principale di questo studio di Fase 2 è di valutare la sicurezza, tollerabilità e prova di fattibilità di due infusioni endovenose una volta alla settimana di 100 mg/kg di ANX005 in soggetti con anemia emolitica autoimmune calda (wAIHA) |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are as follows: • To evaluate the pharmacokinetic (PK) profile of ANX005 in subjects with wAIHA • To evaluate the effect of ANX005 on classical complement pathway inhibition as measured by complement system related biomarkers in subjects with wAIHA • To assess the effect of 2 once-weekly doses of ANX005 on the following disease activity markers in subjects with wAIHA: Hemoglobin, Lactate dehydrogenase (LDH), Total and Indirect bilirubin, Haptoglobin, Reticulocyte count, Platelet count, CRP, Direct Antibody Test (DAT). |
• Valutare il profilo farmacocinetico (PK) di ANX005 in soggetti con wAIHA; • Valutare l'effetto di ANX005 sull'inibizione della via classica del complemento come misurato dai biomarker relativi al sistema del complemento in soggetti con wAIHA • Valutare l'effetto di 2 dosi una volta a settimana di ANX005 sui seguenti marker di attività della malattia in soggetti con wAIHA: o Emoglobina o Lattato deidrogenasi (LDH) o Bilirubina indiretta e totale o Aptoglobina o Conta dei reticolociti o Conta delle piastrine o CRP o Test anticorpi diretti (DAT) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or non-pregnant, non-lactating female = 18 years of age on the day of signing informed consent 2. Diagnosis of wAIHA at least 3 months prior to screening 3. Hgb level > 10.0 g/dL (pre-transfusion) with no alternative explanation for anemia apart from wAIHA at screening 4. Positive direct antiglobulin test (DAT) = 1 + for C3d and IgG 5. Evidence of classical complement pathway activation by one of the below: a. Serum complement component 4 (C4) below the lower limit of normal b. CH50 below the lower limit of normal 6. Evidence of active hemolysis based on at least one of the following: a. LDH above the ULN b. Indirect bilirubin above the ULN c. Haptoglobin below the LLN 7. Vaccinations against encapsulated bacterial organisms (N. meningitidis, H. influenzae and S. pneumoniae) within 5 years prior to screening or subject must be willing to complete vaccinations at least 2 weeks prior to dosing with ANX005. Documentation of vaccinations must be received at the study site in advance of the scheduled screening visit |
1. Maschio o femmina non gravida, non in allattamento di età = 18 anni il giorno della firma del consenso informato 2. Diagnosi di wAIHA almeno 3 mesi prima dello screening 3. Livello di Hgb> 10,0 g / dL (pre-trasfusione) senza alternative spiegazioni per l'anemia a parte wAIHA allo screening 4. Test dell'antiglobulina diretta positivo (DAT) = 1 + per C3d e IgG 5. Prova dell'attivazione della via classica del complemento da parte di uno dei sotto: a. Componente del complemento sierico 4 (C4) al di sotto del limite inferiore della norma b. CH50 al di sotto del limite inferiore del normale 6. Evidenza di emolisi attiva basata su almeno uno dei seguenti: a. LDH sopra l'ULN b. Bilirubina indiretta al di sopra dell'ULN c. Aptoglobina al di sotto del LLN 7. Vaccinazioni contro organismi batterici incapsulati (N. meningitidis, H. influenzae e S.pneumoniae) entro 5 anni prima dello screening o il soggetto deve essere disponibile completare le vaccinazioni almeno 2 settimane prima della somministrazione di ANX005. La documentazione delle vaccinazioni deve essere ricevuta presso il sito dello studio in anticipo dalla visita di screening programmata |
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E.4 | Principal exclusion criteria |
1. History of or current lymphoma or lymphoproliferative disorder requiring therapy 2. Elevated aspartate aminotransferase or alanine aminotransferase levels > 2.5 times the upper limit of normal at screening 3. Platelet count < 30 x 109/L 4. History of cold agglutinin disease or IgM cold agglutinin titer > 1:64 5. History of solid organ, bone marrow, or stem cell transplantation 6. History of splenectomy within the 3 months prior to screening 7. Other wAIHA treatments: - Received rituximab or other anti-CD20 monoclonal antibody < 3 months prior to screening - Receiving steroids > 1 mg/kg of prednisone or equivalent daily at screening 8. Signs and symptoms of, or a diagnosis consistent with, a chronic autoimmune disorder not resulting from primary wAIHA and/or an ANA titer of = 1:160 9. Known genetic deficiencies of the complement cascade system |
1. Anamnesi o attuale linfoma o disturbo linfoproliferativo che richiede terapia 2. Aspartato aminotransferasi o alanina aminotransferasi elevati livelli> 2,5 volte superiore il limite di normalità allo screening 3. Conta piastrinica <30 x 109 / L 4. Anamnesi di malattia da agglutinine fredde o titolo di agglutinine fredde IgM> 1:64 5. Storia di trapianto di organi solidi, midollo osseo o cellule staminali 6. Storia di splenectomia nei 3 mesi precedenti lo screening 7. Altri trattamenti wAIHA: - Ricevuto rituximab o altro anticorpo monoclonale anti-CD20 <3 mesi prima dello screening - Ricezione dose giornaliera di steroidi> 1 mg / kg di prednisone o equivalente allo screening 8. Segni e sintomi di, o una diagnosi coerente con, un cronico disturbo autoimmune non derivante da wAIHA primario e / o un titolo ANA di = 1: 160 9. Carenze genetiche note del sistema a cascata del complemento |
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E.5 End points |
E.5.1 | Primary end point(s) |
Adverse events, infusion related reactions, safety laboratory assessments (serum chemistry, hematology, urine analysis), and vital signs. |
Eventi avversi, reazioni correlate all'infusione, laboratorio di sicurezza valutazioni (chimica del siero, ematologia, analisi delle urine) e segni vitali. |
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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) |
Pharmacokinetic (PK) endpoints are: -Maximum observed serum concentration (Cmax) -Observed time to Cmax (Tmax) -Area under the ANX005 serum concentration-time curve to the last sample (AUC0-t) and extrapolated through infinity -Accumulation ratio -Terminal half-life (t1/2) -Terminal elimination rate constant -Clearance (CL) -Volume of distribution (Vss) Pharmacodynamics (PD) Endpoints: -Hemoglobin -Lactate dehydrogenase (LDH) -Total and Indirect bilirubin -Haptoglobin -Reticulocyte count -Platelet count -Direct Antibody Test (DAT) |
Gli endpoint farmacocinetici (PK) sono: -Massima concentrazione sierica osservata (Cmax) -Tempo osservato a Cmax (Tmax) -Area sotto la curva concentrazione sierica-tempo fino all'ultimo ANX005 campione (AUC0-t) e estrapolato all'infinito -Rapporto di accumulo -Emivita terminale (t1 / 2) -Velocità di eliminazione del terminale costante -Cancellazione (CL) -Volume di distribuzione (Vss) Endpoint farmacodinamici (PD): -Emoglobina -Lattato deidrogenasi (LDH) -Bilirubina totale e indiretta -Haptoglobin -Conteggio dei reticolociti -Conteggio piastrine -Test diretto degli anticorpi (DAT) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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 |
Tolerability, Proof-of-Concept of Intravenous ANX005 in Subjects with Warm Autoimmune Hemolytic Anemia |
Tollerabilità, prova di fattibilità di ANX005 endovena in soggetti con anemia emolitica autoimmune calda |
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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 | No |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Studio a dosi ripetute in aperto |
Open repeat dose study |
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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 | 1 |
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 | 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 | 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 |
Austria |
France |
Germany |
Hungary |
Italy |
Netherlands |
Norway |
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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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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |