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Phase 2 N=158 Randomized Double-blind Treatment

A Study of MHAA4549A in Combination With Oseltamivir Versus Oseltamivir in Participants With Severe Influenza A Infection

Influenza

Enrolled (actual)
158
Serious AEs
19.6%
Results posted
Jun 2018
Primary outcome: Primary: Percentage of Participants With Adverse Events — 80.4; 67.3; 74.5 percentage of participants

Study Design & Population

Study type
Interventional
Phase
Phase 2
Interventions
MHAA4549A (Drug); Oseltamivir (Drug); Placebo (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Genentech, Inc.
Primary completion
May 2017

Outcome Measures

OutcomeResultp-value
PRIMARY
Percentage of Participants With Adverse Events
80.4; 67.3; 74.5
PRIMARY
Number of Participants With Anti-Therapeutic Antibodies (ATA) to MHAA4549A During and Following Administration of MHAA4549A
0; 1; 1; 0; 0; 0
PRIMARY
Time to Normalization of Respiratory Function
4.28; 2.78; 2.65 0.6050
SECONDARY
Percentage of Participants by Clinical Status Using a Categorical Ordinal Outcome
0.0; 0.0; 0.0; 42.6; 38.5; 43.2
SECONDARY
Percentage of Participants With Clinical Failure
14.8; 25.0; 22.7 0.1905
SECONDARY
Percentage of Participants With Clinical Resolution of Abnormal Vital Signs
81.3; 73.3; 66.7 0.6043
SECONDARY
Percentage of Participants Who Died Due to Any Cause
1.9; 3.8; 6.8; 5.6; 7.7; 9.1 0.5379
SECONDARY
Area Under Viral Load-Time Curve (AUEC ) of Influenza A Virus
25.72; 21.99; 25.03 0.2407
SECONDARY
Peak Influenza A Viral Load
5.70; 5.37; 5.28 0.2790
SECONDARY
Duration of Viral Shedding
4.00; 4.63; 4.60 0.7413
SECONDARY
Duration of Hospitalization
8.95; 7.65; 6.69 0.8806
SECONDARY
Duration of Intensive Care Unit (ICU) Stay
4.66; 6.60; 5.29 0.4171
SECONDARY
Percentage of Participants Using Antibiotics for Respiratory Infections
13.0; 11.5; 11.4 0.8240
SECONDARY
Percentage of Participants With Secondary Complications of Influenza
13.0; 15.4; 13.6 0.7219
SECONDARY
Percentage of Participants Readmitted to Hospital Due to Any Cause
1.9; 3.8; 0 0.5379
SECONDARY
Duration of Ventilation
4.11; 7.05; 5.89 0.7827
SECONDARY
Area Under Serum Concentration-Time Curve From Time 0 to Infinity (AUC ) of MHAA4549A
11400; 26700
SECONDARY
Maximum Serum Concentration (Cmax ) of MHAA4549A
916; 2220
SECONDARY
Elimination Half-Life (Terminal t1/2) of MHAA4549A
19.0; 17.8
SECONDARY
Observed Clearance (CL-obs) of MHAA4549A
288; 350
SECONDARY
Observed Steady State Volume of Distribution (Vss_obs) of MHAA4549A
6410; 7450

Summary

This is a randomized, double-blind, placebo-controlled study that will investigate the safety and clinical activity of a single intravenous (IV) dose of MHAA4549A in adult participants hospitalized with severe influenza A in combination with oseltamivir versus a comparator arm of placebo with oseltamivir.

Eligibility Criteria

Inclusion Criteria

  • 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 admission: requirement for O2 supplementation to maintain SpO2 greater than (>) 92 %; or requirement for Positive Pressure Ventilation (PPV)
  • A negative urine or serum pregnancy test for women of childbearing potential within 2 days prior to study treatment
  • Participants of reproductive potential must agree to use acceptable contraceptive measures as per the protocol as a minimum, and local guidelines, if more stringent

Exclusion Criteria

  • Pregnant or lactating women, or women who intend to become pregnant during the study
  • Hypersensitivity to monoclonal antibodies or any constituents (sodium succinate, sucrose, polysorbate 20) of 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
  • Participants 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
  • Participants requiring home or baseline oxygenation therapy
  • Participants with history of chronic lung disease with a documented SpO2 less than (<) 95% off oxygen
  • Participants on chronic dose of corticosteroids exceeding 10 milligrams per day (mg/day) of prednisone or equivalent steroid dose for duration of greater than 14 days within 30 days of entry into study
  • Participants with the following significant immune suppression: bone marrow or solid organ transplant in the previous 12 months; cancer chemotherapy in the previous 12 months, HIV infection with most recent Cluster of Differentiation 4 (CD4) <200 cells per milliliter (cells/mL), or other significant immune suppression as determined by the investigator in discussion with the Sponsor Medical Monitor
  • Participants 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 participant at an unacceptable risk of injury or render the participant unable to meet the requirements of the protocol
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02293863). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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