Study comparing MHAA4549A in combination with oseltamivir versus placebo in combination with oseltamivir for the treatment of severe influenza A infection

• Register: EUCTR
• Last refreshed on: 28 August 2017
• Main ID: EUCTR2014-000461-43-BE
• Date of registration: 05/11/2014
• Prospective Registration: Yes
• Primary sponsor: Genentech Inc.
• Public title: Study comparing MHAA4549A in combination with oseltamivir versus placebo in combination with oseltamivir for the treatment of severe influenza A infection
• Scientific title: 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
• Date of first enrolment: 14/11/2014
• Target sample size: 330
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-000461-43
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Chile, Czech Republic, France, Germany, Hong Kong, Hungary, Italy, Korea, Republic of, Lithuania, Mexico, Netherlands, New Zealand, Peru, Poland, Singapore, South Africa, Spain, Sweden, United Kingdom, United States

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: GENENTECH, Inc. c/o F.Hoffmann-La Roche Ltd

• Name: Trial Information Support Line-TISL
• Affiliation: GENENTECH, Inc. c/o F.Hoffmann-La Roche Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
• Men or women = 18 years of age
• 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 PCR test
• Requirement for oxygen supplementation to maintain SpO2 >92% or PPV within 24 hours of hospital admission
• Negative urine or serum pregnancy test for women of childbearing potential

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 130

Exclusion criteria:
• Pregnant or lactating, or intending to become pregnant during the study
• 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 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
• Onset of influenza symptoms >5 days prior to study treatment
• Patients who have taken more than a total of 6 doses (3 doses of peramivir) of anti-influenza therapy (e.g., oseltamivir, zanamivir,laninamivir, peramivir) in the period from onset of symptoms and prior to study treatment
• Requiring home or baseline oxygenation therapy
• Positive influenza B or influenza A+B infection within 2 weeks prior to study treatment
• Admission >48 hours prior to study treatment
• Any disease or condition that would, in the opinion of the investigator or Sponsor, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Virus Diseases [C02]

Treatment of Influenza
MedDRA version: 19.0 Level: LLT Classification code 10022002 Term: Influenza A virus infection System Organ Class: 100000004862
MedDRA version: 19.0 Level: LLT Classification code 10022001 Term: Influenza (epidemic) System Organ Class: 100000004862
MedDRA version: 19.0 Level: LLT Classification code 10016790 Term: Flu System Organ Class: 100000004862

Intervention(s)

Product Name: MHAA4549A
Product Code: MHAA4549A/RO6876802
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: n.a.
CAS Number: n.a.
Current Sponsor code: MHAA4549A/RO6876802
Other descriptive name: [anti-Influenza A, 39.29]
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Trade Name: Tamiflu
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: OSELTAMIVIR PHOSPHATE
CAS Number: 204255-11-8
Other descriptive name: OSELTAMIVIR PHOSPHATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 75-

Primary Outcome(s)

Secondary Objective: • To measure clinical failure after 24 hours post-infusion of study drug
• To determine the time to clinical resolution of vital signs
• To measure mortality in patients
• To determine changes in the extent and duration of viral shedding in upper respiratory samples
• To measure the duration of hospital and/or intensive care unit stay
• To measure antibiotic usage for respiratory infections
• To measure the frequency and severity of secondary complications of influenza
• To measure duration of positive pressure ventilation
• To measure readmission rates
• To characterize the PK profile of MHAA4549A in serum
• To identify any potential viral resistance to MHAA4549A in influenza A isolates from upper respiratory samples and from tracheal aspirate samples
•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 six mutually exclusive categories on Days 1- 7, 14, and 30.

Primary end point(s): Median time to normalization of respiratory function

Timepoint(s) of evaluation of this end point: The time to normalization of respiratory function will be defined as the time to removal of the patient from oxygen supplementation in order to maintain an oxygen saturation >95%. The analysis of this endpoint will be conducted at the end of the study after all patients have completed all study assessments and the database has been cleaned and closed.

Main Objective: 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 Outcome(s)

Secondary end point(s): • Proportion of patients with clinical failure 24 hours post-infusion of study drug
• Median time to clinical normalization 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 upper respiratory samples
• 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

Timepoint(s) of evaluation of this end point: All secondary endpoint analyses of the total study population will be conducted at the end of the study after all patients have completed all study assessments and the database has been cleaned and closed.

Secondary ID(s)

2014-000461-43-IT

GV29216

Source(s) of Monetary Support

GENENTECH, Inc. c/o F.Hoffmann-La Roche Ltd