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

A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial of MHAA4549A, a Monoclonal Antibody, Administered as Monotherapy for the Treatment of Acute Uncomplicated Seasonal Influenza A Infection in Otherwise Healthy Adults

This is a Phase 2, randomized, double-blind, placebo-controlled single dose study in otherwise healthy adults with acute uncomplicated seasonal influenza A to assess the safety and tolerability, efficacy, and pharmacokinetics of MHAA4549A.

Study Overview

• Status: Completed
• Conditions: Influenza A
• Intervention / Treatment: Drug: MHAA4549A; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 124
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1P 0A2
    • inVentiv Health Clinique
  • British Columbia
    • Vancouver, British Columbia, Canada, V6J 1S3
      • Manna Research Vancouver
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 6Z8
      • Moncton Hospital
  • Ontario
    • Toronto, Ontario, Canada, M9W 4L6
      • Manna Research
  • Quebec
    • Gatineau, Quebec, Canada, J8Y 6S9
      • Q and T Research
• Korea, Republic of
  • Anyang-si, Korea, Republic of, 14068
    • Hallym University Sacred Heart Hospital
  • Bucheon-si,, Korea, Republic of, 420-767
    • Soon Chun Hyang University Hospital Bucheon
  • Incheon, Korea, Republic of
    • Gachon University Gil Hospital
  • Seoul, Korea, Republic of, 02841
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of, 07441
    • Hallym University Kangnam Sacred Heart Hospital
  • Seoul, Korea, Republic of, 08308
    • Korea University Guro Hospital
  • Wonju, Korea, Republic of, 220-701
    • Wonju Christian Hospital
• New Zealand
  • Auckland, New Zealand, 1010
    • Optimal Clinical Trials
  • Auckland, New Zealand, 0612
    • Henderson Medical Centre
  • Dunedin, New Zealand
    • RMC Medical Research Ltd
  • Tauranga, New Zealand, 3143
    • Tauranga Hospital
• South Africa
  • Centurion, South Africa, 1692
    • Johese Clinical Research
  • Durban, South Africa, 4052
    • Durban International Clinical Research Site
  • Durban, South Africa, 4091
    • Vawda Z Private Practice
  • Durban, South Africa, 4092
    • Dr Peter John Sebastian; Dr PJ Sebastian
  • Groenkloof, South Africa, 0181
    • Into Research; Life Groenkloof Hospital Medical Centre
  • Johannesburg, South Africa, 2113
    • Newtown Clinical Research
  • Johannesburg, South Africa, 1500
    • Worthwhile Clinical Trials
  • Kempton Park, South Africa, 1619
    • Clinresco Centres (Pty) Ltd
  • Kempton Park, South Africa, 1619
    • Peermed Clinical Trial Centre
  • Klerksdorp, South Africa, 2574
    • Klerksdorp /Tshepong Hospital Complex
  • Krugersdorp, South Africa, 1739
    • DJW Navorsing
  • Lyttleton, South Africa, 0157
    • I Engelbrecht Research
  • Pretoria Gauteng Province, South Africa, 0087
    • Syzygy Clinical Research; Unit 3 to 7
  • Pretoria-West, South Africa, 0183
    • Jongaie Research
  • Queenswood, South Africa, 0121
    • Queenswood CTC
  • Soweto, South Africa, 2013
    • Wits Clinical Research
  • Welkom, South Africa, 9460
    • Welkom Clinical Trial Centre
• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona
  • Barcelona
    • Terrassa, Barcelona, Spain, 08221
      • Hospital Mutua de Terrassa; Servicio de Oncologia
  • Islas Baleares
    • Palma de Mallorca, Islas Baleares, Spain, 07010
      • Hospital Universitario Son Espases
  • LA Rioja
    • Logroño, LA Rioja, Spain, 26006
      • Hospital San Pedro
  • Vizcaya
    • Galdacao, Vizcaya, Spain, 48960
      • Hospital de Galdakao
• United Kingdom
  • Guildford, United Kingdom, GU2 7XP
    • Surrey Clinical Research Centre; University of Surrey
  • London, United Kingdom, EC1A 7BE
    • Barts and the London NHS Trust.
  • Middlesborough, United Kingdom, TS4 3BW
    • The James Cook University Hospital
• United States
  • Alabama
    • Athens, Alabama, United States, 35611
      • North Alabama Research Center LLC
  • California
    • Costa Mesa, California, United States, 92626
      • WCCT Global, LLC
    • Fountain Valley, California, United States, 92708
      • Lalla-Reddy Medical Corporation
  • Colorado
    • Centennial, Colorado, United States, 80112
      • IMMUNOe Research Centers
  • Florida
    • Doral, Florida, United States, 33166
      • Integrity Clinical Research
    • Edgewater, Florida, United States, 32132
      • Riverside Clinical Research
    • Gainesville, Florida, United States, 32607
      • Sarkis Clinical Trials
    • Hialeah, Florida, United States, 33016
      • The Community Research of South Florida
    • Lauderhill, Florida, United States, 33319
      • Innovative Clinical Research, Inc.
    • Miami, Florida, United States, 33135
      • South Florida Research Center, Inc.
    • Miami, Florida, United States, 33144
      • Oceane7 Clinical Research
    • Saint Cloud, Florida, United States, 34769
      • Central Florida Internists
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital
    • Trinity, Florida, United States, 34655
      • Advanced Research Institute, Inc.
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Cotton O'Neil Clinical Research Center
    • Wichita, Kansas, United States, 67207
      • Heartland Research Associates
    • Wichita, Kansas, United States, 67205
      • Professional Research Network of Kansas
  • Kentucky
    • Hazard, Kentucky, United States, 41701
      • Kentucky Lung Clinic
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • MedPharmics
    • Opelousas, Louisiana, United States, 70570
      • Acadiana Medicine Clinic
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Anne Arundel Medical Center; Anne Arundel Health System
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • UMass Memorial Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48235
      • Sinai Grace Hospital
    • Detroit, Michigan, United States, 48201
      • Detroit Medical Center
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63108
      • Barnes Jewish Hospital
  • Montana
    • Butte, Montana, United States, 59701
      • Mercury Street Medical Group
  • Nebraska
    • La Vista, Nebraska, United States, 68128
      • Barrett Clinic, P.C.
  • New Jersey
    • Princeton, New Jersey, United States, 08540
      • Global Medical Institutes, LLC
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates
  • Rhode Island
    • Providence, Rhode Island, United States, 02908
      • Center For Medical Research LLC
  • South Carolina
    • Boiling Springs, South Carolina, United States, 29316
      • Emergency MD
  • Tennessee
    • Franklin, Tennessee, United States, 37067
      • HCCA Clinical Research Solutions
    • Knoxville, Tennessee, United States, 37920
      • Clinical Research Solutions PC
    • Smyrna, Tennessee, United States, 37167
      • Clinical Research Solutions, LLC
  • Texas
    • Galveston, Texas, United States, 77555
      • University Of Texas Medical Branch At Galveston
    • Houston, Texas, United States, 77058
      • Centex Studies
    • Pharr, Texas, United States
      • Centex Studies

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Otherwise healthy participants
• Positive test for influenza A infection
• No more than 72 hours elapsed between onset of influenza-like illness and start of study drug
• Presence of at least one moderate or severe constitutional symptom such as headache, myalgia, fever, chills, fatigue, anorexia, or nausea PLUS one moderate or severe respiratory symptom such as cough, sore throat, or rhinorrhea
• For women of childbearing potential: negative pregnancy test and agreement to use acceptable contraceptive methods for at least 120 days after study drug administration
• For men: agreement to use acceptable contraceptive methods for at least 30 days after study drug administration

Exclusion Criteria:

• Creatinine clearance less than or equal to (</=) 80 milliliters per minute (mL/min)
• Any significant medical conditions or laboratory abnormalities
• Clinical signs and symptoms consistent with otitis, bronchitis, sinusitis, or pneumonia or active bacterial infection
• Use of antiviral therapy in the period from onset of influenza-like illness and prior to enrollment
• Pregnancy at Screening or is currently pregnant or breastfeeding
• Investigational therapy within 30 days or 5 half-lives prior to start of study drug, whichever is greater
• Prior anti-influenza monoclonal antibody use
• Receipt of a nasal influenza A vaccine within 14 days prior to Screening
• Positive test for influenza B or influenza A+B within 2 weeks prior to study drug
• History of significant tobacco use or drug/alcohol abuse
• Chronic use of oral or inhaled corticosteroids within 30 days prior to Screening
• Autoimmune disease, known immunodeficiency of any cause, or use of immunosuppressive medications
• History of any chronic respiratory condition
• Human immunodeficiency virus (HIV) with cluster of differentiation (CD) 4 count </= 200 cells per milliliter (cells/mL) in the past 12 months
• Serious infection requiring oral or IV antibiotics within 14 days prior to Screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MHAA4549A 3600 milligrams (mg); Participants will receive single-dose MHAA4549A, 3600 mg, by intravenous (IV) administration.	Drug: MHAA4549A; MHAA4549A will be administered as a single dose by IV administration.
Experimental: MHAA4549A 8400 mg; Participants will receive single-dose MHAA4549A, 8400 mg, by IV administration.	Drug: MHAA4549A; MHAA4549A will be administered as a single dose by IV administration.
Placebo Comparator: Placebo; Participants will receive single-dose placebo by IV administration.	Drug: Placebo; Placebo will be administered as a single dose by IV administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Adverse Events (AEs)	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.	Baseline to Day 100

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Requiring Hospitalization for Influenza-Related Complications		Baseline to Day 100
Duration of Hospitalization for Influenza-Related Complications		Baseline to Day 100
Percentage of Participants Requiring Antibiotics for Secondary Bacterial Respiratory Infections	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."	Baseline to Day 100
Percentage of Participants With Complications of Influenza	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."	Baseline to Day 100
Percentage of Participants With Influenza A Relapse/Reinfection		Baseline to Day 100
Area Under the Concentration-Time Curve (AUC) of MHAA4549A	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).	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)
Maximum Serum Concentration (Cmax) of MHAA4549A		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)
Time to Alleviation of Symptoms of Influenza A Infection	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.	Baseline to Day 14
Percentage of Participants With Influenza-Related Deaths		Baseline to Day 100

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 12, 2016
• Primary Completion (Actual): November 13, 2017
• Study Completion (Actual): November 13, 2017

Study Registration Dates

• First Submitted: December 3, 2015
• First Submitted That Met QC Criteria: December 3, 2015
• First Posted (Estimate): December 7, 2015

Study Record Updates

• Last Update Posted (Actual): January 8, 2019
• Last Update Submitted That Met QC Criteria: December 14, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: GV29893; 2016-000425-40 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No