Clinical Trials List
Protocol NumberGV29216
2016-03-01 - 2017-07-31
Phase II
Study ended4
ICD-10J09.X2
Influenza due to identified novel influenza A virus with other respiratory manifestations
ICD-10J09
Influenza due to certain identified influenza viruses
A PHASE 2 RANDOMIZED, DOUBLE-BLIND PLACEBO CONTROLLED TRIAL OF MHAA4549A, A MONOCLONAL ANTIBODY IN COMBINATION WITH OSELTAMIVIR VERSUS OSELTAMIVIR FOR TREATMENT OF SEVERE INFLUENZA A INFECTION
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Trial Applicant
PPD DEVELOPMENT (HK) LIMITED
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Sponsor
Genentech, Inc
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Chung-Hao Huang Division of Infectious Disease
- Shang-Yi Lin Division of Infectious Disease
- 林蔚如 Division of Infectious Disease
- Po-Liang Lu Division of Infectious Disease
- 鄭宇辰 Division of Infectious Disease
The Actual Total Number of Participants Enrolled
0 Study ended
The Actual Total Number of Participants Enrolled
0 Study ended
Co-Principal Investigator
- Chun-Hua Wang Division of Thoracic Medicine
- Horng-Chyuan Lin Division of Thoracic Medicine
- Shu-Min Lin Division of Thoracic Medicine
- 黃集仁 Division of Emergency Medicine
- Chun-Liang Chou Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Study ended
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- Han-Lin Hsu Division of Thoracic Medicine
- Chih-Hsin Lee Division of Thoracic Medicine
- Shian-Jiun Lin Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
2 Study ended
Audit
None
Condition/Disease
Influenza A
Objectives
Primary:
• 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.
Secondary:
To compare the clinical status of patients at Days 1−7, 14, and 30 using an ordinal
outcome with six clinical statuses. Patients will be categorized into one of the
following six mutually exclusive categories on Days 1−7, 14, and 30
1. Death;
2. In the ICU;
3. Non-ICU hospitalization, requiring supplemental oxygen;
4. Non-ICU hospitalization, not requiring supplemental oxygen;
5. Not hospitalized, but unable to resume normal activities; or
6. Not hospitalized with full resumption of normal activities
• To measure clinical failure, as defined in Section 3.3.3, after 24 hours post infusion
of study drug
• To determine the time to clinical resolution of abnormal vital signs
• To measure mortality in patients
• To determine changes in the extent and duration of viral burden in nasopharyngeal
samples as a measure of the pharmacodynamic response
• To measure the duration of hospital and/or ICU stay
• To measure antibiotic usage for respiratory infections
• To measure the frequency and severity of the following secondary complications of
influenza:
– Pneumonia (hospital acquired pneumonia [HAP]/ ventilator acquired
pneumonia [VAP])
– Exacerbations of chronic lung disease
– Myocarditis
– Acute respiratory distress syndrome (ARDS)
– Otitis media
– Other related complications
– Readmission rates at 30 and 60 days after study treatment
• To measure duration of PPV
• To measure readmission rates
Test Drug
MHAA4549A
Active Ingredient
MHAA4549A
Dosage Form
Injection
Dosage
500mg/10mL (50mg/mL)
Endpoints
Primary:
• Median time to normalization of respiratory function.
Secondary:
Clinical status at Days 1-7, 14, and 30 categorizing proportion of patients in each
of the 6 pre-defined categories
• Proportion of patients with clinical failure after 24 hours post-infusion of study drug
• Median time to clinical resolution 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 nasopharyngeal samples
• Proportion of patients with detectable infection
• 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
• Median time to normalization of respiratory function.
Secondary:
Clinical status at Days 1-7, 14, and 30 categorizing proportion of patients in each
of the 6 pre-defined categories
• Proportion of patients with clinical failure after 24 hours post-infusion of study drug
• Median time to clinical resolution 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 nasopharyngeal samples
• Proportion of patients with detectable infection
• 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
Inclution Criteria
Patients must meet the following criteria for study entry:
• Men or women ≥ 18 years of age on day of signing informed consent or obtaining surrogate consent from an authorized representative
• 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 polymerase chain reaction (PCR) test
• One of the following markers of severity within 24 hours of hospital admission:
– Requirement for PPV, OR
– Requirement for O2 supplementation to maintain SpO2 > 92% (Source documentation
should show that the patient’s SpO2 was less than 92% off oxygen. Source documentation may consist of either a SpO2 off oxygen with a value below 92% or a documentation of the Investigator’s rationale in lieu of this SpO2 documentation.)
• A negative urine or serum pregnancy test for women of childbearing potential
• Patients of reproductive potential must agree to use reliable means of contraception as described below as a minimum (adherence to more stringent local requirements may be required):
– For women who are not postmenopausal (postmenopausal defined as ≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use two adequate methods of contraception, including at least one method with a failure rate of < 1% per year, during the treatment period and for at least 120 days after the last dose of study drug
Abstinence is only acceptable if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of contraception.
Barrier methods must always be supplemented with the use of a spermicide.
Examples of contraceptive methods with a failure rate of < 1% per year include tubal ligation, male sterilization, hormonal implants, proper use of combined oral or injected hormonal contraceptives, and certain intrauterine devices.
– For men: agreement to remain abstinent or use a condom during the treatment period and for at least 30 days after the last dose of study drug and agreement to refrain from donating sperm during this same period
Men with a pregnant partner must agree to remain abstinent or use a condom for the duration of the pregnancy.
Abstinence is only acceptable if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
Non-reproductive potential is defined below (but could be superseded by local definitions, if they are more stringent):
– Women who are postmenopausal (≥ 12 months of non-therapy-induced amenorrhea)
– Women who are surgically sterile (i.e., hysterectomy, complete bilateral oophorectomy)
– Men who are surgically sterile (castration)
• Men or women ≥ 18 years of age on day of signing informed consent or obtaining surrogate consent from an authorized representative
• 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 polymerase chain reaction (PCR) test
• One of the following markers of severity within 24 hours of hospital admission:
– Requirement for PPV, OR
– Requirement for O2 supplementation to maintain SpO2 > 92% (Source documentation
should show that the patient’s SpO2 was less than 92% off oxygen. Source documentation may consist of either a SpO2 off oxygen with a value below 92% or a documentation of the Investigator’s rationale in lieu of this SpO2 documentation.)
• A negative urine or serum pregnancy test for women of childbearing potential
• Patients of reproductive potential must agree to use reliable means of contraception as described below as a minimum (adherence to more stringent local requirements may be required):
– For women who are not postmenopausal (postmenopausal defined as ≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use two adequate methods of contraception, including at least one method with a failure rate of < 1% per year, during the treatment period and for at least 120 days after the last dose of study drug
Abstinence is only acceptable if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of contraception.
Barrier methods must always be supplemented with the use of a spermicide.
Examples of contraceptive methods with a failure rate of < 1% per year include tubal ligation, male sterilization, hormonal implants, proper use of combined oral or injected hormonal contraceptives, and certain intrauterine devices.
– For men: agreement to remain abstinent or use a condom during the treatment period and for at least 30 days after the last dose of study drug and agreement to refrain from donating sperm during this same period
Men with a pregnant partner must agree to remain abstinent or use a condom for the duration of the pregnancy.
Abstinence is only acceptable if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
Non-reproductive potential is defined below (but could be superseded by local definitions, if they are more stringent):
– Women who are postmenopausal (≥ 12 months of non-therapy-induced amenorrhea)
– Women who are surgically sterile (i.e., hysterectomy, complete bilateral oophorectomy)
– Men who are surgically sterile (castration)
Exclusion Criteria
Patients who meet any of the following criteria will be excluded from study entry:
• Pregnant or lactating, or intending to become pregnant during the study
− Women who are not postmenopausal (postmenopausal defined as ≥ 12 months of non-therapy-induced amenorrhea) or who are not surgically sterile must have a negative urine or serum pregnancy test result within 2 days prior to study treatment
• Hypersensitivity to monoclonal antibodies or to any constituents (sodium succinate, sucrose, polysorbate 20) of MHAA4549A study drug
• Hypersensitivity to the active substance or to any excipients of oseltamivir
• Investigational therapy within the 30 days prior to study treatment
• Received prior therapy with any anti-influenza monoclonal antibody therapy (including MHAA4549A) within 8 months prior to study treatment
• Current treatment (within 7 days of dosing) with probenecid, amantadine, or rimantidine
• Patients who have taken more than a total of 6 doses (3 doses for peramivir) of anti-influenza therapy (e.g., oseltamivir, zanamivir, laninamivir, peramivir) in the period from onset of symptoms and prior to study treatment
• Admission > 48 hours prior to study treatment
• Onset of influenza symptoms (including fever, chills, malaise, dry cough, loss of appetite, myalgias, coryza, or nausea) > 5 days prior to study treatment
• Positive influenza B or influenza A + B infection within 2 weeks prior to study treatment
• High probability of mortality in the next 48 hours as determined by the investigator
• Patient requiring home or baseline oxygenation therapy
• Patient with history of chronic lung disease with a documented SpO2 < 95% off oxygen
• Patient on chronic dose of corticosteroids exceeding 10 mg/day of prednisone or equivalent steroid dose for a duration of greater than 14 days within 30 days of entry into study
• Creatinine clearance ≤10 mL/min
• Patients who received nasally administered influenza A vaccine within 7 days prior to screening
• Patients with the following significant immune suppression:
– Bone marrow or solid organ transplant in the previous 12 months
– Cancer chemotherapy in the previous 12 month
– Human immunodeficiency virus (HIV) infection with most recent CD4 < 200 cells/mL
– Other significant immune suppression as determined by the investigator in discussion with the Sponsor Medical Monitor or representative
• Patient on extracorporeal membrane oxygenation (ECMO) at time of randomization
• Any disease or condition that would, in the opinion of the site investigator or Sponsor, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol
• Pregnant or lactating, or intending to become pregnant during the study
− Women who are not postmenopausal (postmenopausal defined as ≥ 12 months of non-therapy-induced amenorrhea) or who are not surgically sterile must have a negative urine or serum pregnancy test result within 2 days prior to study treatment
• Hypersensitivity to monoclonal antibodies or to any constituents (sodium succinate, sucrose, polysorbate 20) of MHAA4549A study drug
• Hypersensitivity to the active substance or to any excipients of oseltamivir
• Investigational therapy within the 30 days prior to study treatment
• Received prior therapy with any anti-influenza monoclonal antibody therapy (including MHAA4549A) within 8 months prior to study treatment
• Current treatment (within 7 days of dosing) with probenecid, amantadine, or rimantidine
• Patients who have taken more than a total of 6 doses (3 doses for peramivir) of anti-influenza therapy (e.g., oseltamivir, zanamivir, laninamivir, peramivir) in the period from onset of symptoms and prior to study treatment
• Admission > 48 hours prior to study treatment
• Onset of influenza symptoms (including fever, chills, malaise, dry cough, loss of appetite, myalgias, coryza, or nausea) > 5 days prior to study treatment
• Positive influenza B or influenza A + B infection within 2 weeks prior to study treatment
• High probability of mortality in the next 48 hours as determined by the investigator
• Patient requiring home or baseline oxygenation therapy
• Patient with history of chronic lung disease with a documented SpO2 < 95% off oxygen
• Patient on chronic dose of corticosteroids exceeding 10 mg/day of prednisone or equivalent steroid dose for a duration of greater than 14 days within 30 days of entry into study
• Creatinine clearance ≤10 mL/min
• Patients who received nasally administered influenza A vaccine within 7 days prior to screening
• Patients with the following significant immune suppression:
– Bone marrow or solid organ transplant in the previous 12 months
– Cancer chemotherapy in the previous 12 month
– Human immunodeficiency virus (HIV) infection with most recent CD4 < 200 cells/mL
– Other significant immune suppression as determined by the investigator in discussion with the Sponsor Medical Monitor or representative
• Patient on extracorporeal membrane oxygenation (ECMO) at time of randomization
• Any disease or condition that would, in the opinion of the site investigator or Sponsor, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol
The Estimated Number of Participants
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Taiwan
20 participants
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Global
330 participants
