Trial Outcomes & Findings for A Study of MHAA4549A as Monotherapy for Acute Uncomplicated Seasonal Influenza A in Otherwise Healthy Adults (NCT NCT02623322)

NCT ID: NCT02623322

Last Updated: 2019-01-08

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 124 participants
• Primary outcome timeframe: Baseline to Day 100
• Results posted on: 2019-01-08

Participant Flow

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).

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.

Participant milestones

Measure	Placebo Participants received single-dose placebo by intravenous (IV) administration.	MHAA4549A 3600 mg Participants received single-dose MHAA4549A, 3600 milligrams (mg), by IV administration.	MHAA4549A 8400 mg Participants received single-dose MHAA4549A, 8400 mg, by IV administration.
Overall Study STARTED	43	41	40
Overall Study COMPLETED	41	40	40
Overall Study NOT COMPLETED	2	1	0

Reasons for withdrawal

Measure	Placebo Participants received single-dose placebo by intravenous (IV) administration.	MHAA4549A 3600 mg Participants received single-dose MHAA4549A, 3600 milligrams (mg), by IV administration.	MHAA4549A 8400 mg Participants received single-dose MHAA4549A, 8400 mg, by IV administration.
Overall Study Lost to Follow-up	2	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Placebo n=43 Participants Participants received single-dose placebo by intravenous (IV) administration.	MHAA4549A 3600 mg n=41 Participants Participants received single-dose MHAA4549A, 3600 milligrams (mg), by IV administration.	MHAA4549A 8400 mg n=40 Participants Participants received single-dose MHAA4549A, 8400 mg, by IV administration.	Total n=124 Participants Total of all reporting groups
Age, Continuous	39.3 years STANDARD_DEVIATION 10.8 • n=5 Participants	36.5 years STANDARD_DEVIATION 12.5 • n=7 Participants	35.0 years STANDARD_DEVIATION 13.6 • n=5 Participants	37.0 years STANDARD_DEVIATION 12.4 • n=4 Participants
Sex: Female, Male Female	27 Participants n=5 Participants	22 Participants n=7 Participants	22 Participants n=5 Participants	71 Participants n=4 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	19 Participants n=7 Participants	18 Participants n=5 Participants	53 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic or Latino	2 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	40 Participants n=5 Participants	38 Participants n=7 Participants	38 Participants n=5 Participants	116 Participants n=4 Participants
Race/Ethnicity, Customized Not Stated	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Asian	2 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	7 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	13 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants	35 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized White	27 Participants n=5 Participants	26 Participants n=7 Participants	23 Participants n=5 Participants	76 Participants n=4 Participants
Race/Ethnicity, Customized Multiple	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline to Day 100

Population: The safety population included all participants randomized to treatment.

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.

Outcome measures

Measure	Placebo n=43 Participants Participants received single-dose placebo by intravenous (IV) administration.	MHAA4549A 3600 mg n=41 Participants Participants received single-dose MHAA4549A, 3600 milligrams (mg), by IV administration.	MHAA4549A 8400 mg n=40 Participants Participants received single-dose MHAA4549A, 8400 mg, by IV administration.
Percentage of Participants With Adverse Events (AEs)	30.2 percentage of participants	39.0 percentage of participants	30.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Day 100

Population: The intent-to-treat infected (ITTI) population included all randomized participants who had an influenza A infection confirmed by central polymerase chain reaction (PCR).

Outcome measures

Measure	Placebo n=33 Participants Participants received single-dose placebo by intravenous (IV) administration.	MHAA4549A 3600 mg n=35 Participants Participants received single-dose MHAA4549A, 3600 milligrams (mg), by IV administration.	MHAA4549A 8400 mg n=31 Participants Participants received single-dose MHAA4549A, 8400 mg, by IV administration.
Percentage of Participants Requiring Hospitalization for Influenza-Related Complications	0 percentage of participants	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Baseline to Day 100

Population: The intent-to-treat infected (ITTI) population included all randomized participants who had an influenza A infection confirmed by central polymerase chain reaction (PCR).

Outcome measures

Measure	Placebo n=33 Participants Participants received single-dose placebo by intravenous (IV) administration.	MHAA4549A 3600 mg n=35 Participants Participants received single-dose MHAA4549A, 3600 milligrams (mg), by IV administration.	MHAA4549A 8400 mg n=31 Participants Participants received single-dose MHAA4549A, 8400 mg, by IV administration.
Duration of Hospitalization for Influenza-Related Complications	0 days	0 days	0 days

SECONDARY outcome

Timeframe: Baseline to Day 100

Population: The intent-to-treat infected (ITTI) population included all randomized participants who had an influenza A infection confirmed by central PCR.

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."

Outcome measures

Measure	Placebo n=33 Participants Participants received single-dose placebo by intravenous (IV) administration.	MHAA4549A 3600 mg n=35 Participants Participants received single-dose MHAA4549A, 3600 milligrams (mg), by IV administration.	MHAA4549A 8400 mg n=31 Participants Participants received single-dose MHAA4549A, 8400 mg, by IV administration.
Percentage of Participants Requiring Antibiotics for Secondary Bacterial Respiratory Infections	3.0 percentage of participants Interval 0.32 to 11.28	0 percentage of participants Interval 0.0 to 6.37	0 percentage of participants Interval 0.0 to 7.16

SECONDARY outcome

Timeframe: Baseline to Day 100

Population: ITTI population included all randomized participants who had an influenza A infection confirmed by central PCR.

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."

Outcome measures

Measure	Placebo n=33 Participants Participants received single-dose placebo by intravenous (IV) administration.	MHAA4549A 3600 mg n=35 Participants Participants received single-dose MHAA4549A, 3600 milligrams (mg), by IV administration.	MHAA4549A 8400 mg n=31 Participants Participants received single-dose MHAA4549A, 8400 mg, by IV administration.
Percentage of Participants With Complications of Influenza	3.0 percentage of participants Interval 0.32 to 11.28	0 percentage of participants Interval 0.0 to 6.37	0 percentage of participants Interval 0.0 to 7.16

SECONDARY outcome

Timeframe: Baseline to Day 100

Population: ITTI population included all randomized participants who had an influenza A infection confirmed by central PCR.

Outcome measures

Measure	Placebo n=33 Participants Participants received single-dose placebo by intravenous (IV) administration.	MHAA4549A 3600 mg n=35 Participants Participants received single-dose MHAA4549A, 3600 milligrams (mg), by IV administration.	MHAA4549A 8400 mg n=31 Participants Participants received single-dose MHAA4549A, 8400 mg, by IV administration.
Percentage of Participants With Influenza A Relapse/Reinfection	0 percentage of participants	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: 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)

Population: Data were collected for this outcome measure.

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).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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)

Population: The pharmacokinetic (PK)-evaluable population included all participants who received MHA4549A.

Outcome measures

Measure	Placebo n=40 Participants Participants received single-dose placebo by intravenous (IV) administration.	MHAA4549A 3600 mg n=37 Participants Participants received single-dose MHAA4549A, 3600 milligrams (mg), by IV administration.	MHAA4549A 8400 mg Participants received single-dose MHAA4549A, 8400 mg, by IV administration.
Maximum Serum Concentration (Cmax) of MHAA4549A	1050 mcg/mL Standard Deviation 299	2190 mcg/mL Standard Deviation 581	—

SECONDARY outcome

Timeframe: Baseline to Day 14

Population: ITTI population included all randomized participants who had an influenza A infection confirmed by central PCR. Data are reported for evaluable participants.

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.

Outcome measures

Measure	Placebo n=33 Participants Participants received single-dose placebo by intravenous (IV) administration.	MHAA4549A 3600 mg n=35 Participants Participants received single-dose MHAA4549A, 3600 milligrams (mg), by IV administration.	MHAA4549A 8400 mg n=31 Participants Participants received single-dose MHAA4549A, 8400 mg, by IV administration.
Time to Alleviation of Symptoms of Influenza A Infection Total Symptom Score of <=1	117.30 hours Interval 108.62 to 157.15	153.80 hours Interval 125.52 to 175.23	145.82 hours Interval 132.98 to 156.68
Time to Alleviation of Symptoms of Influenza A Infection Total Symptom Score of <=7	44.50 hours Interval 27.23 to 58.65	74.18 hours Interval 64.32 to 87.98	65.59 hours Interval 44.12 to 87.23

SECONDARY outcome

Timeframe: Baseline to Day 100

Population: The safety population included all participants randomized to treatment.

Outcome measures

Measure	Placebo n=43 Participants Participants received single-dose placebo by intravenous (IV) administration.	MHAA4549A 3600 mg n=41 Participants Participants received single-dose MHAA4549A, 3600 milligrams (mg), by IV administration.	MHAA4549A 8400 mg n=40 Participants Participants received single-dose MHAA4549A, 8400 mg, by IV administration.
Percentage of Participants With Influenza-Related Deaths	0 percentage of participants	0 percentage of participants	0 percentage of participants

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

MHAA4549A 3600 mg

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

MHAA4549A 8400 mg

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=43 participants at risk Participants received single-dose placebo by intravenous (IV) administration.	MHAA4549A 3600 mg n=41 participants at risk Participants received single-dose MHAA4549A, 3600 milligrams (mg), by IV administration.	MHAA4549A 8400 mg n=40 participants at risk Participants received single-dose MHAA4549A, 8400 mg, by IV administration.
Cardiac disorders Atrial fibrillation	0.00% 0/43 • Baseline to Day 100 The safety population included all participants randomized to treatment.	0.00% 0/41 • Baseline to Day 100 The safety population included all participants randomized to treatment.	2.5% 1/40 • Baseline to Day 100 The safety population included all participants randomized to treatment.

Other adverse events

Measure	Placebo n=43 participants at risk Participants received single-dose placebo by intravenous (IV) administration.	MHAA4549A 3600 mg n=41 participants at risk Participants received single-dose MHAA4549A, 3600 milligrams (mg), by IV administration.	MHAA4549A 8400 mg n=40 participants at risk Participants received single-dose MHAA4549A, 8400 mg, by IV administration.
Gastrointestinal disorders Nausea	4.7% 2/43 • Baseline to Day 100 The safety population included all participants randomized to treatment.	7.3% 3/41 • Baseline to Day 100 The safety population included all participants randomized to treatment.	7.5% 3/40 • Baseline to Day 100 The safety population included all participants randomized to treatment.
Infections and infestations Bronchitis	2.3% 1/43 • Baseline to Day 100 The safety population included all participants randomized to treatment.	7.3% 3/41 • Baseline to Day 100 The safety population included all participants randomized to treatment.	2.5% 1/40 • Baseline to Day 100 The safety population included all participants randomized to treatment.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	2.3% 1/43 • Baseline to Day 100 The safety population included all participants randomized to treatment.	2.4% 1/41 • Baseline to Day 100 The safety population included all participants randomized to treatment.	5.0% 2/40 • Baseline to Day 100 The safety population included all participants randomized to treatment.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: (+41) 616878333

Email: global.trial_information@roche.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER