E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Bullous Pemphigoid |
Pemfigoide bolloso |
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E.1.1.1 | Medical condition in easily understood language |
Rare, autoimmune, chronic relapsing skin disorder characterized by blistering, hives and itching |
Malattia della pelle recidivante rara, autoimmune, cronica caratterizzata da vesciche, orticaria e prurito |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10006567 |
E.1.2 | Term | Bullous pemphigoid |
E.1.2 | System Organ Class | 100000004858 |
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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 compare the clinical efficacy of benralizumab with placebo in participants with symptomatic BP |
Confrontare l’efficacia clinica di benralizumab rispetto al placebo nei partecipanti con PB sintomatico |
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E.2.2 | Secondary objectives of the trial |
1. To compare the effect of benralizumab with placebo on supportive measures of clinical efficacy in participants with symptomatic BP up to Week 36. 2. To compare the effect of benralizumab with placebo on clinical efficacy in participants with symptomatic BP up to Week 16. 3. To estimate the PK and immunogenicity of benralizumab in participants with BP. |
1. Confrontare l’effetto di benralizumab rispetto al placebo sulle misure di supporto di efficacia clinica nei partecipanti con PB sintomatico fino alla Settimana 36 2. Confrontare l’effetto di benralizumab rispetto al placebo sull’efficacia clinica nei partecipanti con BP sintomatico fino alla Settimana 16 3. Stimare la PK e l’immunogenicità di benralizumab nei partecipanti con PB |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Adult participants = 18 years of age 2. Participants must have clinical features of BP (eg, urticarial or eczematous or erythematous plaques, bullae, pruritus) at the screening visit and confirmed diagnosis with histology, direct immunofluorescence, and serology at randomization. Required for inclusion: (a) Histology. (b) Positive direct immunofluorescence (from skin biopsy) (IgG and/or C3 at the basement membrane zone). (c) AND at least one of the following serologic assessments positive (all assessed from participant’s blood sample): (i) indirect immunofluorescence (IgG on the roof of salt- split skin). (ii) positive serology on ELISA for BPAG1 (230-kd). (iii) positive serology on ELISA for BPAG2 (180-kd). 3. BPDAI activity score = 24 at the screening and randomization visits. 4. Candidate for systemic corticosteroid therapy. |
1. Partecipanti adulti di età =18 anni 2. I partecipanti devono presentare caratteristiche cliniche di pemfigoide bolloso (bullous pemphigoid, BP) come ad es. placche urticanti o eczematose o eritematose, bolle, e prurito alla visita di screening e diagnosi confermata con istologia, immunofluorescenza diretta, e sierologia al momento della randomizzazione. Requisiti per l’inclusione: (a) Istologia. (b) Immunofluorescenza diretta positiva (dalla biopsia cutanea) (IgG e/o C3 lungo la zona della membrana basale). (c) E almeno una delle seguenti valutazioni sierologiche positive (tutte valutate in base al campione ematico del partecipante): (i) immunofluorescenza indiretta (IgG sulla parte superiore della salt split skin). (ii) sierologia positiva in ELISA per BPAg1 (230 kD). (iii) sierologia positiva in ELISA per BPAg2 (180 kD). 3. Punteggio di attività BPDAI =24 alle visite di screening e di randomizzazione. 4. Candidato per terapia corticosteroidea sistemica. |
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E.4 | Principal exclusion criteria |
1. Forms of BP other than classic, predominantly cutaneous BP: eg, mucous membrane BP, epidermolysis bullosa acquisita, Brunsting-Perry BP, p200 BP, p105 BP, BP with 2. Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, psychiatric, or major physical impairment that is not stable in the opinion of the Investigator and could: (a) Affect the safety of the participant throughout the study. (b) Influence the findings of the studies or their interpretations. (c) Prevent the participant’s ability to complete the entire duration of study. (d) Impact the participant’s ability to complete the required PRO assessments. 3. Current malignancy, or history of malignancy, except for: (a) Participants who have had basal cell carcinoma, localized squamous cell carcinoma of the skin, or in situ carcinoma of the cervix are eligible provided that the participant is in remission and curative therapy was completed at least 12 months prior to the date informed consent, and assent when applicable was obtained. (b) Participants who have had other malignancies are eligible provided that the participant is in remission and curative therapy was completed at least 5 years prior to the date informed consent, and assent when applicable, was obtained. 4. History of anaphylaxis to any biologic therapy or vaccine. 5. History of Guillain-Barré syndrome. 6. A helminth parasitic infection diagnosed within 24 weeks prior to the date informed consent is obtained that has not been treated with, or has failed to respond to standard of care therapy. 7. Any clinically significant abnormal findings in physical examination, vital signs, hematology, clinical chemistry, or urinalysis during screening, which in the opinion of the Investigator, may put the participant at risk because of his/her participation in the study, or may influence the results of the study, or the participant’s ability to complete entire duration of the study. 8. Any clinically significant cardiac disease or any electrocardiogram (ECG) abnormality obtained during the screening/run-in period, which in the opinion of the Investigator may put the participant at risk or interfere with study assessments. 9. Current active liver disease. (a) Chronic stable hepatitis B and C (including positive testing for hepatitis B surface antigen or hepatitis C antibody), or other stable chronic liver disease are acceptable if subject otherwise meets eligibility criteria. Stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice, or cirrhosis. (b) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level =3 times the upper limit of normal, confirmed by repeated testing during screening period. 10. A history of known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test. 11. Use of immunosuppressive medication (including but not limited to: methotrexate, cyclosporine, azathioprine, 12. Receipt of immunoglobulin or blood products within 30 days prior to the date informed 13. Receipt of any marketed (eg, omalizumab) or investigational biologic within 4 months or 5 half-lives prior to the date informed consent is obtained, whichever is longer. 14. Known history of allergy or reaction to any component of the IP formulation. 15. |
1. Forme di BP diverse dal classico BP preval cutaneo: come ad es. BP membrane mucose, epidermolisi bollosa acquisita, BP di Brunsting-Perry, BP p200, BP p105, BP con pemfigo volgare concomitante, BP indotto da farmaci (ad es. insorgenza o attuale aggravamento da inibitori dell’enzima di conversione dell’angiotesina, penicillamina, furosemide, fenacetina, inibitori della dipeptidil-peptidasi 4 o alcune terapie immuno-oncologiche). 2. Qualsiasi disturbo, cardiov, gastrointest, epatico, renale, neurologico, muscoloschel, infettivo, endocrino, metabolico, ematologico, psichiatrico o menomazione fisica grave, che non sia stabile a giudizio del PI e che potrebbe: (a) Compromettere la sicurezza del partecipante per tutta la durata dello studio. (b) Influenzare i risultati degli studi o le loro interpretazioni. (c) Impedire al partecipante di completare lo studio nella sua intera durata. (d) Compromettere la capacità del partecipante di completare le valutazioni degli esiti riferiti dal paziente (patient-reported outcome, PRO) richieste. 3. Tumore maligno attuale o anamnesi di tumore maligno, eccetto: (a) I partecipanti che hanno sofferto di carcinoma a cellule basali, carcinoma cutaneo a cellule squamose localizzato o carcinoma in situ della cervice sono idonei a condizione che il partecipante sia in remissione e la terapia curativa sia stata completata almeno 12 mesi prima della data del consenso informato, e che sia stato ottenuto il consenso, ove applicabile. (b) I partecipanti che hanno avuto altri tumori maligni sono idonei a condizione che il partecipante sia in remissione e che la terapia curativa sia stata completata almeno 5 anni prima della data del consenso informato, 4. Anamnesi di anafilassi a qualsiasi terapia con biofarmaci o vaccino. 5. Anamnesi di sindrome di Guillain-Barré. 6. Un’infezione parassitaria elmintica diagnosticata nelle 24 settimane precedenti alla data di ottenimento del consenso informato, che non è stata trattata 7. Qualsiasi riscontro anomalo clinicamente significativo nell’esame obiettivo, nei segni vitali, nell’ematologia, nella chimica clinica o nell’esame dell’urina durante lo screening, che a giudizio del PI potrebbe mettere a rischio il 8. Qualsiasi cardiopatia clinicamente significativa o qualsiasi anomalia dell'ECG ottenuta durante screening/run-in, che a giudizio del PI potrebbe mettere il partecipante a rischio o interferire con le valutazioni dello studio. 9. Attuale malattia epatica attiva. (a) Epatite B e C cronica stabile o altra malattia epatica cronica stabile sono accettabili se il soggetto altrimenti soddisfa i criteri di idoneità (b) Livello di ALT o AST =3 volte il limite sup dell’intervallo normale, confermato da test ripetuti durante il periodo di screening. Un aumento transitorio del livello di AST/ALT che si risolve entro la data della randomizzazione è accettabile se, a giudizio del PI, il soggetto non presenta una malattia epatica attiva e soddisfa altri criteri di idoneità. 10. Anamnesi di disturbo da immunodeficienza noto, compreso un test positivo per il virus dell’immunodeficienza umana (HIV). 11. Uso di farmaci immunosoppressori (inclusi, a titolo esemp ma non esaust: metotrexato, ciclosporina, azatioprina, corticosteroide intramuscolare (IM) a rilascio prolungato o qualsiasi terapia antinfiammatoria sperimentale) nei 3 mesi prec data di ottenimento del CI. 12. Ricezione di immunoglobulina o di prodotti ematici nei 30 giorni precedenti alla data di ottenimento del consenso informato. 13. Ricezione di qualsiasi biofarmaco commercializzato (ad es. omalizumab) o sperimentale nei 4 mesi o nelle 5 emivite pre data di ottenimento del CI a seconda di quale sia il periodo più lungo. 14. Anamnesi nota di allergia o reazione a qualsiasi componente della formulazione del prodotto sperimentale. 1.. |
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E.5 End points |
E.5.1 | Primary end point(s) |
A binary response, whereby a responder is defined as a participant who is in partial or complete remission while off OCS for = 2 months at Week 36. |
Una risposta binaria, in cui un risponditore è definito come un partecipante che è parziale o completo remissione durante l'assenza di OCS per = 2 mesi alla settimana 36. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
at Week 36 |
Alla settimana 36 |
|
E.5.2 | Secondary end point(s) |
Key secondary : • Proportion of participants who remain relapse-free up to Week 36. • Cumulative OCS exposure (mg/kg) from baseline to Week 36. • Change from baseline in BPDAI activity score at Week 36. • Change from baseline in BPDAI-Pruritus at Week 36. • Cumulative OCS exposure (mg/kg) from baseline to Week 16. |
Secondario chiave: • Proporzione di partecipanti che rimangono liberi da ricadute fino alla settimana 36. • Esposizione cumulativa a OCS (mg / kg) dal basale alla settimana 36. • Variazione rispetto al basale nel punteggio di attività BPDAI alla settimana 36. • Variazione rispetto al basale in BPDAI-Pruritus alla settimana 36. • Esposizione cumulativa a OCS (mg / kg) dal basale alla settimana 16. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
various time points as per protocol |
diversi come da protocollo |
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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 | No |
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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | 2 |
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 | 28 |
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 |
Australia |
Israel |
Japan |
United States |
Bulgaria |
France |
Germany |
Italy |
Spain |
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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
|
Last Patient Last Visit |
Ultima Visita Ultimo Paziente |
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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 | 7 |
E.8.9.1 | In the Member State concerned days | 25 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |