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] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10022001 |
E.1.2 | Term | Influenza (epidemic) |
E.1.2 | System Organ Class | 100000004862 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10016790 |
E.1.2 | Term | Flu |
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 |
to determine the time to normalization of respiratory function of patients dosed with MHAA4549A in combination with oseltamivir compared to patients dosed with placebo and oseltamivir. |
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E.2.2 | Secondary objectives of the trial |
• To measure clinical failure after 24 hours post-infusion of study drug
• To determine the time to clinical resolution of vital signs
• To measure mortality in patients
• To determine changes in the extent and duration of viral shedding in upper respiratory samples
• To measure the duration of hospital and/or intensive care unit stay
• To measure antibiotic usage for respiratory infections
• To measure the frequency and severity of secondary complications of influenza
• To measure duration of positive pressure ventilation
• To measure readmission rates
• To characterize the PK profile of MHAA4549A in serum
• To identify any potential viral resistance to MHAA4549A in influenza A isolates from upper respiratory samples and from tracheal aspirate samples
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
DNA REPOSITORY SUBSTUDY IN ASSOCIATION WITH MHAA4549A STUDY GV29216, dated 11th March 2015, version 3.0
The primary objective of this study is to perform exploratory analyses to generate hypotheses identifying genes associated with treatment response, toxicity, or disease risk |
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E.3 | Principal inclusion criteria |
• Men or women ≥ 18 years of age
• Diagnosis of influenza A where a Sponsor-approved influenza test is used as an aid in diagnosis. A Sponsor-approved influenza test includes:
Influenza antigen test or Influenza PCR test
• Requirement for oxygen supplementation to maintain SpO2 >92% or PPV within 24 hours of hospital admission
• Negative urine or serum pregnancy test for women of childbearing potential
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E.4 | Principal exclusion criteria |
• Pregnant or lactating, or intending to become pregnant during the study
• Hypersensitivity to monoclonal antibodies or to the active substance or any excipients of MHAA4549A study drug
• Hypersensitivity to the active substance or to any excipients of oseltamivir
• Investigational therapy within 30 days prior to study treatment
• Received prior therapy with any anti-influenza monoclonal antibody therapy including MHAA4549A 8 months prior to study treatment
• Onset of influenza symptoms >5 days prior to study treatment
• Patients who have taken more than a total of 6 doses (3 doses of peramivir) of anti-influenza therapy (e.g., oseltamivir, zanamivir, peramivir) in the period from onset of symptoms and prior to study treatment
• Requiring home or baseline oxygenation therapy
• Positive influenza B or influenza A+B infection within 2 weeks prior to study treatment
• Admission >48 hours prior to study treatment
• Any disease or condition that would, in the opinion of the investigator or Sponsor, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol
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E.5 End points |
E.5.1 | Primary end point(s) |
Median time to normalization of respiratory function |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The time to normalization of respiratory function will be defined as the time to removal of the patient from oxygen supplementation in order to maintain an oxygen saturation >95%. The analysis of this endpoint will be conducted at the end of the study after all patients have completed all study assessments and the database has been cleaned and closed. |
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E.5.2 | Secondary end point(s) |
• Proportion of patients with clinical failure 24 hours post-infusion of study drug
• Median time to clinical normalization of vital signs
• Hazard ratio for mortality at Day 14, Day 30 and Day 60.
• Mean and median AUC of viral load
• Mean and median peak viral load
• Median duration of viral shedding in upper respiratory samples
• Median duration of hospitalization
• Median duration of ICU stay
• Proportion of patients requiring antibiotics for respiratory indications during study
• Proportion of patients with influenza secondary complications
• Median duration of ventilation
• Proportion of patients who are readmitted by Day 30 and Day 60 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
All secondary endpoint analyses of the total study population will be conducted at the end of the study after all patients have completed all study assessments and the database has been cleaned and closed.
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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 | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Optional DNA Repository Substudy |
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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 | 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) | Yes |
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 | 63 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 70 |
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 |
Argentina |
Australia |
Belgium |
Brazil |
Bulgaria |
Canada |
Chile |
Czech Republic |
France |
Germany |
Hong Kong |
Hungary |
Italy |
Korea, Republic of |
Lithuania |
Mexico |
Netherlands |
New Zealand |
Peru |
Poland |
Singapore |
South Africa |
Spain |
Sweden |
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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If it is the last visit of the last subject, please enter “LVLS”. If it is not LVLS provide the definition: The end of the study is defined as the first day when all patients have had a study completion visit or early termination visit or have otherwise been discontinued from the study. End of study is defined by last visit of the last subject . |
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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 | 11 |
E.8.9.1 | In the Member State concerned days | |
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 | 11 |