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A Study of MHAA4549A as Monotherapy for Acute Uncomplicated Seasonal Influenza A in Otherwise Healthy Adults

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02623322
Recruitment Status : Completed
First Posted : December 7, 2015
Results First Posted : January 8, 2019
Last Update Posted : January 8, 2019
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Influenza A
Interventions Drug: MHAA4549A
Drug: Placebo
Enrollment 124
Recruitment Details The study was conducted at 34 investigational sites in 6 countries including the United States (15 centers), South Africa (12 centers), Canada, Spain, New Zealand (2 centers in each country), and Great Britain (1 center).
Pre-assignment Details Randomization was stratified by onset of influenza-like illness (≤ 36 hours and > 36 hours) and a permuted block randomization method was used to obtain an approximate 1:1:1 ratio of subjects in the 3600 mg MHAA4549A, 8400 mg MHAA4549A, and placebo strata.
Arm/Group Title Placebo MHAA4549A 3600 mg MHAA4549A 8400 mg
Hide Arm/Group Description Participants received single-dose placebo by intravenous (IV) administration. Participants received single-dose MHAA4549A, 3600 milligrams (mg), by IV administration. Participants received single-dose MHAA4549A, 8400 mg, by IV administration.
Period Title: Overall Study
Started 43 41 40
Completed 41 40 40
Not Completed 2 1 0
Reason Not Completed
Lost to Follow-up             2             1             0
Arm/Group Title Placebo MHAA4549A 3600 mg MHAA4549A 8400 mg Total
Hide Arm/Group Description Participants received single-dose placebo by intravenous (IV) administration. Participants received single-dose MHAA4549A, 3600 milligrams (mg), by IV administration. Participants received single-dose MHAA4549A, 8400 mg, by IV administration. Total of all reporting groups
Overall Number of Baseline Participants 43 41 40 124
Hide Baseline Analysis Population Description
The safety population included all participants randomized to treatment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 43 participants 41 participants 40 participants 124 participants
39.3  (10.8) 36.5  (12.5) 35.0  (13.6) 37.0  (12.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 43 participants 41 participants 40 participants 124 participants
Female
27
  62.8%
22
  53.7%
22
  55.0%
71
  57.3%
Male
16
  37.2%
19
  46.3%
18
  45.0%
53
  42.7%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 43 participants 41 participants 40 participants 124 participants
Hispanic or Latino
2
   4.7%
3
   7.3%
2
   5.0%
7
   5.6%
Not Hispanic or Latino
40
  93.0%
38
  92.7%
38
  95.0%
116
  93.5%
Not Stated
1
   2.3%
0
   0.0%
0
   0.0%
1
   0.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 43 participants 41 participants 40 participants 124 participants
Asian
2
   4.7%
4
   9.8%
1
   2.5%
7
   5.6%
Black or African American
13
  30.2%
7
  17.1%
15
  37.5%
35
  28.2%
Native Hawaiian or Other Pacific Islander
1
   2.3%
2
   4.9%
0
   0.0%
3
   2.4%
White
27
  62.8%
26
  63.4%
23
  57.5%
76
  61.3%
Multiple
0
   0.0%
0
   0.0%
1
   2.5%
1
   0.8%
Unknown
0
   0.0%
2
   4.9%
0
   0.0%
2
   1.6%
1.Primary Outcome
Title Percentage of Participants With Adverse Events (AEs)
Hide Description An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not considered related to the study drug.
Time Frame Baseline to Day 100
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants randomized to treatment.
Arm/Group Title Placebo MHAA4549A 3600 mg MHAA4549A 8400 mg
Hide Arm/Group Description:
Participants received single-dose placebo by intravenous (IV) administration.
Participants received single-dose MHAA4549A, 3600 milligrams (mg), by IV administration.
Participants received single-dose MHAA4549A, 8400 mg, by IV administration.
Overall Number of Participants Analyzed 43 41 40
Measure Type: Number
Unit of Measure: percentage of participants
30.2 39.0 30.0
2.Secondary Outcome
Title Percentage of Participants Requiring Hospitalization for Influenza-Related Complications
Hide Description [Not Specified]
Time Frame Baseline to Day 100
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat infected (ITTI) population included all randomized participants who had an influenza A infection confirmed by central polymerase chain reaction (PCR).
Arm/Group Title Placebo MHAA4549A 3600 mg MHAA4549A 8400 mg
Hide Arm/Group Description:
Participants received single-dose placebo by intravenous (IV) administration.
Participants received single-dose MHAA4549A, 3600 milligrams (mg), by IV administration.
Participants received single-dose MHAA4549A, 8400 mg, by IV administration.
Overall Number of Participants Analyzed 33 35 31
Measure Type: Number
Unit of Measure: percentage of participants
0 0 0
3.Secondary Outcome
Title Duration of Hospitalization for Influenza-Related Complications
Hide Description [Not Specified]
Time Frame Baseline to Day 100
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat infected (ITTI) population included all randomized participants who had an influenza A infection confirmed by central polymerase chain reaction (PCR).
Arm/Group Title Placebo MHAA4549A 3600 mg MHAA4549A 8400 mg
Hide Arm/Group Description:
Participants received single-dose placebo by intravenous (IV) administration.
Participants received single-dose MHAA4549A, 3600 milligrams (mg), by IV administration.
Participants received single-dose MHAA4549A, 8400 mg, by IV administration.
Overall Number of Participants Analyzed 33 35 31
Measure Type: Number
Unit of Measure: days
0 0 0
4.Secondary Outcome
Title Percentage of Participants Requiring Antibiotics for Secondary Bacterial Respiratory Infections
Hide Description Participants with antibiotic usage for secondary bacterial respiratory infections were identified by counting participants with AEs containing the terms, “pneumonia, lung, myocarditis, ARDS (acute respiratory distress syndrome), otitis media, or respiratory.”
Time Frame Baseline to Day 100
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat infected (ITTI) population included all randomized participants who had an influenza A infection confirmed by central PCR.
Arm/Group Title Placebo MHAA4549A 3600 mg MHAA4549A 8400 mg
Hide Arm/Group Description:
Participants received single-dose placebo by intravenous (IV) administration.
Participants received single-dose MHAA4549A, 3600 milligrams (mg), by IV administration.
Participants received single-dose MHAA4549A, 8400 mg, by IV administration.
Overall Number of Participants Analyzed 33 35 31
Measure Type: Number
Number (80% Confidence Interval)
Unit of Measure: percentage of participants
3.0
(0.32 to 11.28)
0
(0.00 to 6.37)
0
(0.00 to 7.16)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, MHAA4549A 3600 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3031
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in event rates (Wald)
Estimated Value -3.03
Confidence Interval (2-Sided) 80%
-12.25 to 6.19
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, MHAA4549A 8400 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3324
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in event rates (Wald)
Estimated Value -3.03
Confidence Interval (2-Sided) 80%
-12.82 to 6.76
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants With Complications of Influenza
Hide Description Participants with complications of influenza were identified by counting participants with AEs containing the terms, “pneumonia, lung, myocarditis, ARDS (acute respiratory distress syndrome), otitis media, or respiratory.”
Time Frame Baseline to Day 100
Hide Outcome Measure Data
Hide Analysis Population Description
ITTI population included all randomized participants who had an influenza A infection confirmed by central PCR.
Arm/Group Title Placebo MHAA4549A 3600 mg MHAA4549A 8400 mg
Hide Arm/Group Description:
Participants received single-dose placebo by intravenous (IV) administration.
Participants received single-dose MHAA4549A, 3600 milligrams (mg), by IV administration.
Participants received single-dose MHAA4549A, 8400 mg, by IV administration.
Overall Number of Participants Analyzed 33 35 31
Measure Type: Number
Number (80% Confidence Interval)
Unit of Measure: percentage of participants
3.0
(0.32 to 11.28)
0
(0.00 to 6.37)
0
(0.00 to 7.16)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, MHAA4549A 3600 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3031
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in event rates (Wald)
Estimated Value -3.03
Confidence Interval (2-Sided) 80%
-12.25 to 6.19
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, MHAA4549A 8400 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3324
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in event rates (Wald)
Estimated Value -3.03
Confidence Interval (2-Sided) 80%
-12.82 to 6.76
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Participants With Influenza A Relapse/Reinfection
Hide Description [Not Specified]
Time Frame Baseline to Day 100
Hide Outcome Measure Data
Hide Analysis Population Description
ITTI population included all randomized participants who had an influenza A infection confirmed by central PCR.
Arm/Group Title Placebo MHAA4549A 3600 mg MHAA4549A 8400 mg
Hide Arm/Group Description:
Participants received single-dose placebo by intravenous (IV) administration.
Participants received single-dose MHAA4549A, 3600 milligrams (mg), by IV administration.
Participants received single-dose MHAA4549A, 8400 mg, by IV administration.
Overall Number of Participants Analyzed 33 35 31
Measure Type: Number
Unit of Measure: percentage of participants
0 0 0
7.Secondary Outcome
Title Area Under the Concentration-Time Curve (AUC) of MHAA4549A
Hide Description The AUC is a measure of the plasma concentration of the drug over time. It is used to characterize drug absorption. AUC was measured in micrograms times hours per milliliter (mcg*h/mL).
Time Frame Up to Day 100 (collections scheduled pre-dose [0 hours]; 60 minutes post-dose; and on Days 3, 5, 7, 30, and 100 post-dose; infusion duration = 2 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
Data were collected for this outcome measure.
Arm/Group Title MHAA4549A 3600 mg MHAA4549A 8400 mg
Hide Arm/Group Description:
Participants received single-dose MHAA4549A, 3600 milligrams (mg), by IV administration.
Participants received single-dose MHAA4549A, 8400 mg, by IV administration.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
8.Secondary Outcome
Title Maximum Serum Concentration (Cmax) of MHAA4549A
Hide Description [Not Specified]
Time Frame Up to Day 100 (collections scheduled pre-dose [0 hours]; 60 minutes post-dose; and on Days 3, 5, 7, 30, and 100 post-dose; infusion duration = 2 hours)
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic (PK)−evaluable population included all participants who received MHA4549A.
Arm/Group Title MHAA4549A 3600 mg MHAA4549A 8400 mg
Hide Arm/Group Description:
Participants received single-dose MHAA4549A, 3600 milligrams (mg), by IV administration.
Participants received single-dose MHAA4549A, 8400 mg, by IV administration.
Overall Number of Participants Analyzed 40 37
Mean (Standard Deviation)
Unit of Measure: mcg/mL
1050  (299) 2190  (581)
9.Secondary Outcome
Title Time to Alleviation of Symptoms of Influenza A Infection
Hide Description Time to alleviation of all 7 symptoms (i.e., nasal congestion, sore throat, cough, aches, fatigue, headaches, chills/sweats) was assessed using a rating scale of 0 (none), 1 (mild), 2 (moderate), or 3 (severe) for each symptom. The outcome was defined in two ways: time to a total symptom score of <=1 and time to a total symptom score of <=7. Resolution had to be maintained for 24 hours without use of symptom relief medications. For participants who were enrolled with mild symptoms, the symptom score had to be reduced by one point during the study duration.
Time Frame Baseline to Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
ITTI population included all randomized participants who had an influenza A infection confirmed by central PCR. Data are reported for evaluable participants.
Arm/Group Title Placebo MHAA4549A 3600 mg MHAA4549A 8400 mg
Hide Arm/Group Description:
Participants received single-dose placebo by intravenous (IV) administration.
Participants received single-dose MHAA4549A, 3600 milligrams (mg), by IV administration.
Participants received single-dose MHAA4549A, 8400 mg, by IV administration.
Overall Number of Participants Analyzed 33 35 31
Median (80% Confidence Interval)
Unit of Measure: hours
Total Symptom Score of <=1 Number Analyzed 33 participants 35 participants 31 participants
117.30
(108.62 to 157.15)
153.80
(125.52 to 175.23)
145.82
(132.98 to 156.68)
Total Symptom Score of <=7 Number Analyzed 33 participants 34 participants 31 participants
44.50
(27.23 to 58.65)
74.18
(64.32 to 87.98)
65.59
(44.12 to 87.23)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, MHAA4549A 3600 mg
Comments Total Symptom Score of <=1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7858
Comments [Not Specified]
Method Wilcoxon
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.92
Confidence Interval (2-Sided) 80%
0.62 to 1.37
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, MHAA4549A 8400 mg
Comments Total Symptom Score of <=1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5170
Comments [Not Specified]
Method Wilcoxon
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.90
Confidence Interval (2-Sided) 80%
0.59 to 1.36
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, MHAA4549A 3600 mg
Comments Total Symptom Score of <=7
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0312
Comments [Not Specified]
Method Wilcoxon
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.63
Confidence Interval (2-Sided) 80%
0.45 to 0.89
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, MHAA4549A 8400 mg
Comments Total Symptom Score of <=7
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2044
Comments [Not Specified]
Method Wilcoxon
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.74
Confidence Interval (2-Sided) 80%
0.53 to 1.04
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Percentage of Participants With Influenza-Related Deaths
Hide Description [Not Specified]
Time Frame Baseline to Day 100
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants randomized to treatment.
Arm/Group Title Placebo MHAA4549A 3600 mg MHAA4549A 8400 mg
Hide Arm/Group Description:
Participants received single-dose placebo by intravenous (IV) administration.
Participants received single-dose MHAA4549A, 3600 milligrams (mg), by IV administration.
Participants received single-dose MHAA4549A, 8400 mg, by IV administration.
Overall Number of Participants Analyzed 43 41 40
Measure Type: Number
Unit of Measure: percentage of participants
0 0 0
Time Frame Baseline to Day 100
Adverse Event Reporting Description The safety population included all participants randomized to treatment.
 
Arm/Group Title Placebo MHAA4549A 3600 mg MHAA4549A 8400 mg
Hide Arm/Group Description Participants received single-dose placebo by intravenous (IV) administration. Participants received single-dose MHAA4549A, 3600 milligrams (mg), by IV administration. Participants received single-dose MHAA4549A, 8400 mg, by IV administration.
All-Cause Mortality
Placebo MHAA4549A 3600 mg MHAA4549A 8400 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/43 (0.00%)   0/41 (0.00%)   0/40 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo MHAA4549A 3600 mg MHAA4549A 8400 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/43 (0.00%)   0/41 (0.00%)   1/40 (2.50%) 
Cardiac disorders       
Atrial fibrillation  1  0/43 (0.00%)  0/41 (0.00%)  1/40 (2.50%) 
1
Term from vocabulary, MedDRA version 20.1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo MHAA4549A 3600 mg MHAA4549A 8400 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/43 (9.30%)   7/41 (17.07%)   6/40 (15.00%) 
Gastrointestinal disorders       
Nausea  1  2/43 (4.65%)  3/41 (7.32%)  3/40 (7.50%) 
Infections and infestations       
Bronchitis  1  1/43 (2.33%)  3/41 (7.32%)  1/40 (2.50%) 
Respiratory, thoracic and mediastinal disorders       
Oropharyngeal pain  1  1/43 (2.33%)  1/41 (2.44%)  2/40 (5.00%) 
1
Term from vocabulary, MedDRA version 20.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: (+41) 616878333
EMail: global.trial_information@roche.com
Layout table for additonal information
Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT02623322     History of Changes
Other Study ID Numbers: GV29893
2016-000425-40 ( EudraCT Number )
First Submitted: December 3, 2015
First Posted: December 7, 2015
Results First Submitted: October 31, 2018
Results First Posted: January 8, 2019
Last Update Posted: January 8, 2019