E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients hospitalized with influenza caused by Type A strains |
pazienti ricoverati con influenza causata da ceppi di Tipo A |
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E.1.1.1 | Medical condition in easily understood language |
Influenza (flu) |
Influenza |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10022002 |
E.1.2 | Term | Influenza A virus infection |
E.1.2 | System Organ Class | 100000004862 |
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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 |
1. To evaluate the effect of MEDI8852 administered in conjunction with oseltamivir and the effect of oseltamivir alone in reducing time to normalization of respiratory function 2. To compare the safety and tolerability of a single intravenous(IV) dose of MEDI8852 administered in conjunction with oseltamivir to the safety and tolerability of oseltamivir alone |
Valutare l¿effetto di MEDI8852 somministrato in combinazione con oseltamivir e l¿effetto di oseltamivir in monoterapia nel ridurre il tempo alla normalizzazione della funzione respiratoria 2. Confrontare la sicurezza e la tollerabilit¿ di una dose singola endovenosa (EV) di MEDI8852 somministrato in combinazione con oseltamivir con la sicurezza e la tollerabilit¿ di oseltamivir in monoterapia
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E.2.2 | Secondary objectives of the trial |
To evaluate/determine: 1. the effect of MEDI8852 in reducing severity of clinical status 2. the effect of MEDI8852 in reducing time to clinical resolution of individual vital sign abnormalities 3.the effect of MEDI8852 in reducing NEWS 4.the effect of MEDI8852 in reducing time to hospital discharge 5.the effect of MEDI8852 in reducing time to ICU discharge 6.the effect of MEDI8852 in reducing the duration of mechanical ventilation 7.the effect of MEDI8852 in reducing the rates of ICU admission from the general ward 8.the effect of MEDI8852 on all-cause mortality 9.the effect of MEDI8852 on all-cause hospital re-admission rates during the study 10.the effect of MEDI8852 in reducing the duration and quantity of viral shedding by by quantitative reverse transcriptase (qRT-PCR) over time 11. To evaluate the serum concentration and PK of MEDI8852 12. To evaluate the serum ADA of MEDI8852 |
Valutare: 1. l¿effetto di MEDI8852 nel ridurre la gravit¿ dello stato clinico 2.l¿effetto di MEDI8852 nel ridurre il tempo alla risoluzione clinica delle anomalie individuali nei segni vitali 3.l¿effetto di MEDI8852 nel ridurre il NEWS 4.l¿effetto di MEDI8852 nel ridurre il tempo alla dimissione dall¿ospedale 5.l¿effetto di MEDI8852 nel ridurre il tempo alla dimissione dall¿UTI 6.l¿effetto di MEDI8852 nel ridurre la durata della ventilazione meccanica 7.l¿effetto di MEDI8852 nel ridurre i tassi di ricovero nell¿UTI dal reparto generale 8. Determinare l¿effetto di MEDI8852 sulla mortalit¿ per qualsiasi causa 9. Determinare l¿effetto di MEDI8852 sui tassi di nuovo ricovero ospedaliero per qualsiasi causa durante lo studio 10. Valutare l¿effetto di MEDI8852 nel ridurre la durata e la quantit¿ di diffusione virale misurata mediante reazione a catena quantitativa della polimerasi-trascrittasi inversa (qRT-PCR) nel tempo |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age 18 years or older at the time of screening. 2. Written informed consent and any locally required authorization obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations. 3. Females of childbearing potential who are sexually active with a nonsterilized male partner must have evidence of not being pregnant upon enrollment and have a negative pregnancy test prior to administration of investigational product. 4. Hospitalized = 72 hours prior to receipt of a positive diagnostic test for influenza A; confirmed with positive rapid antigen test, or confirmed with culture, polymerase chain reaction, or antigen testing at the study site. 5. Onset of influenza symptoms = 144 hours (= 6 days) prior to randomization. 6. Receiving supplemental oxygen. 7. Expected to participate in the study through Day 60. |
1. Età 18 anni o più al momento dello screening. 2. consenso informato scritto e qualsiasi autorizzazione richiesta a livello locale (ad esempio, assicurazione sanitaria Portabilità e Accountability Act [HIPAA] negli Stati Uniti, i dati sulla direttiva in Europa) ottenuto dal soggetto / rappresentante legale prima di eseguire qualsiasi procedure relative al protocollo, comprese le valutazioni di screening. 3. Donne in età fertile che sono sessualmente attive con un partner non sterile devono avere la prova di non essere in stato di gravidanza al momento dell'iscrizione e avere un esito negativo del test di gravidanza prima della somministrazione del prodotto sperimentale. ¿ Donne in età fertile sono definite come coloro che non sono chirurgicamente sterili (Vale a dire, legatura delle tube bilaterale, ovariectomia bilaterale o isterectomia completa), premenarchal, o post-menopausa (definita come 12 mesi senza mestruazioni senza causa medica alternativa). 4. Ricoverato = 72 ore prima del ricevimento di un test diagnostico positivo per l'influenza A; confermata con test rapido dell'antigene positivo (forniti o approvati dallo sponsor), o confermata con la cultura, la reazione a catena della polimerasi, o test dell'antigene al luogo di studio. 5. L'insorgenza di sintomi influenzali = 144 ore (= 6 giorni) prima della randomizzazione. 6. evr ricevuto ossigeno supplementare. 7. tenuti a partecipare allo studio attraverso Giorno 60. |
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E.4 | Principal exclusion criteria |
1. Any condition that, in the opinion of the investigator, would interfere with evaluation of study drugs or interpretation of subject safety or study results. 2. Concurrent enrollment in another clinical study involving an investigational treatment. 3. Hospitalized > 72 hours (> 3 days) prior to receipt of a positive diagnostic test for influenza A. 4. Receipt of > 72 hours or > 6 doses of treatment with a neuraminidase (NA) inhibitor. 5. Receipt of any investigational antiviral medications within 30 days prior to study drug dosing. 6. Previous receipt of an influenza mAb within past 100 days. 7. Pregnant or nursing female. 8. History of allergic disease or reactions likely to be exacerbated by any components of the study drugs (MEDI8852 or oseltamivir). 9. Diagnosis of influenza B infection within 14 days prior to randomization. 10. Employees of the sponsor, clinical study site, or any other individuals involved with the conduct of the study, or immediate family members of such individuals. |
1. Qualsiasi condizione che, a giudizio dello sperimentatore, potrebbe interferire con la valutazione di farmaci in studio o l'interpretazione della sicurezza del soggetto o dei risultati di studio. 2. l'iscrizione contemporanea a un altro studio clinico che coinvolge un trattamento sperimentale. 3. ospedalizzati> 72 ore (> 3 giorni) prima del ricevimento di un test diagnostico positivo per influenza A. 4. Ricevuta di> 72 ore o> 6 dosi di trattamento con una neuraminidasi (NA) inibitore. 5. Ricevuto farmaci antivirali sperimentale nei 30 giorni precedenti al dosaggio del farmaco in studio. 6. ricezione precedente di un mAb influenzale entro ultimi 100 giorni. 7. Donna incinta o in allattamento. 8. storia di malattie allergiche o reazioni che possono essere aggravate da qualsiasi componente del farmaco in studio (MEDI8852 o oseltamivir). 9. La diagnosi di infezione da influenza B entro 14 giorni prima della randomizzazione. 10. I dipendenti dello sponsor, sito studio clinico, o qualsiasi altra persone coinvolte con il Esecuzione dello studio, o stretti familiari di tali individui. |
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E.5 End points |
E.5.1 | Primary end point(s) |
a. Time to normalization of respiratory function, defined as: i. For subjects without underlying chronic lung disease and not on supplemental oxygen prior to hospitalization, an oxygen saturation of = 95% for 24 hours on room air ii. For subjects with underlying chronic lung disease or on supplemental oxygen prior to hospitalization, a return to their baseline oxygen saturation and/or supplemental oxygen requirements as recorded during the 2 months prior to admission and not associated with a concurrent respiratory illness or the onset of influenza symptoms for 24 hours
2. Safety of MEDI8852 Treatment-emergent serious adverse events (TESAEs) treatment-emergent adverse events (TEAEs) and treatmentemergent adverse events of special interest (TEAESIs)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Efficacy of MEDI8852. Respiratory function will be followed through Day 14. 2. Safety of MEDI8852 a. TEAEs through Day 28 b. TESAEs and TEAESIs through Day 60 |
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E.5.2 | Secondary end point(s) |
1. Ordinal outcome of clinical status 2. Time to clinical resolution of individual vital signs abnormalities, including temperature, respiration rate, heart rate, and blood pressure 3. Change in NEWS from baseline to Day 3 4. Time to hospital discharge 5. Time to ICU discharge 6. Duration of mechanical ventilation 7. Rate of ICU admission from the general ward 8. All-cause mortality 9. Rate of all-cause re-admission during the study 10. Quantification of influenza viral shedding over time by qRT-PCR 11. MEDI8852 serum concentration and PK parameters 12. MEDI8852 ADA response in serum |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Day 7 2-11. Followed through Day 60. |
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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 | 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 | 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 | 15 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 98 |
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 |
Canada |
Israel |
Mexico |
Russian Federation |
South Africa |
Turkey |
United States |
Belgium |
Bulgaria |
Czechia |
Denmark |
Estonia |
Finland |
France |
Germany |
Hungary |
Italy |
Netherlands |
Poland |
Romania |
Spain |
Sweden |
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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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LVLS |
ultima visita utlimo 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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |