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

NCT ID: NCT02293863

Last Updated: 2018-06-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 168 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-14
• Study Completion Date: 2017-05-23

Brief 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.

Conditions

Influenza

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

A: MHAA4549A 3600 mg + Oseltamivir

Participants will receive a single low IV dose of MHAA4549A on Day 1 and standard oseltamivir therapy for minimum of 5 days.

Group Type: EXPERIMENTAL

Oseltamivir

Intervention Type: DRUG

Participants will receive oseltamivir capsule either 75 mg or 150 mg BID orally for minimum of 5 days. Dosage and administration should follow local prescribing information for oseltamivir.

MHAA4549A

Intervention Type: DRUG

Participants will receive a single dose of MHAA4549A by IV infusion on Day 1

B: MHAA4549A 8400 mg + Oseltamivir

Participants will receive a single high IV dose of MHAA4549A on Day 1 and standard oseltamivir therapy for minimum of 5 days.

Group Type: EXPERIMENTAL

Oseltamivir

Intervention Type: DRUG

Participants will receive oseltamivir capsule either 75 mg or 150 mg BID orally for minimum of 5 days. Dosage and administration should follow local prescribing information for oseltamivir.

MHAA4549A

Intervention Type: DRUG

Participants will receive a single dose of MHAA4549A by IV infusion on Day 1

C: Placebo + Oseltamivir

Participants will receive a single IV dose of placebo matched to MHAA4549A on Day 1 and standard oseltamivir therapy (75 or 150 mg BID) for minimum of 5 days.

Group Type: PLACEBO_COMPARATOR

Oseltamivir

Intervention Type: DRUG

Participants will receive oseltamivir capsule either 75 mg or 150 mg BID orally for minimum of 5 days. Dosage and administration should follow local prescribing information for oseltamivir.

Placebo

Intervention Type: DRUG

Participants will receive a single IV dose of placebo matched to MHAA4549A on Day 1

Interventions

Oseltamivir

Participants will receive oseltamivir capsule either 75 mg or 150 mg BID orally for minimum of 5 days. Dosage and administration should follow local prescribing information for oseltamivir.

Intervention Type: DRUG

Placebo

Participants will receive a single IV dose of placebo matched to MHAA4549A on Day 1

Intervention Type: DRUG

MHAA4549A

Participants will receive a single dose of MHAA4549A by IV infusion on Day 1

Intervention Type: DRUG

Other Intervention Names

Tamiflu

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

CHU St Pierre (St Pierre)

Brussels, , Belgium

Hospital Erasme; Neurologie

Brussels, , Belgium

UZ Leuven Gasthuisberg

Leuven, , Belgium

CHU UCL Mont-Godinne

Mont-godinne, , Belgium

Santa Casa de Misericordia; de Belo Horizonte

Belo Horizonte, Minas Gerais, Brazil

Hospital Sao Vicente de Paulo

Passo Fundo, Rio Grande do Sul, Brazil

PUC Campinas

Campinas, São Paulo, Brazil

FUNFARME

São José do Rio Preto, São Paulo, Brazil

Hospital Alemao Oswaldo Cruz; Oncologia

São Paulo, São Paulo, Brazil

Hospital Edmundo Vasconcelos

Vila Clementino, São Paulo, Brazil

MHAT "Dr. Tota Venkova"- Gabrovo

Gabrovo, , Bulgaria

University Multiprofile Hospital for Active Treatment "St. George"

Plovdiv, , Bulgaria

SHATPPD Dr. Dimitar Gramatikov, Ruse Ltd.

Rousse, , Bulgaria

Multiprofile Hospital for Active Treatment AKTA-MEDIKA EOOD

Sevlievo, , Bulgaria

MHAT Lyulin EAD, Department of internal diseases

Sofia, , Bulgaria

MHAT TOKUDA SOFIA/ICU-Intensive Care Unit

Sofia, , Bulgaria

5th Multifunctional Hospital for Active treatment

Sofia, , Bulgaria

Military Medical Academy- MHAT

Sofia, , Bulgaria

University Multiprofile Hospital for Active Treatment and Emergency Medicine N. I. Pirogov EAD

Sofia, , Bulgaria

MBAL St Marina Dep Pulmonology, ICU

Varna, , Bulgaria

Multiprofile District Hospital for Active Treatment Dr. Stefan Cherkezov AD

Veliko Tarnovo, , Bulgaria

Peter Lougheed Centre

Calgary, Alberta, Canada

Alberta Health Services

Calgary, Alberta, Canada

Foothills Medical Centre

Calgary, Alberta, Canada

Rockyview General Hospital

Calgary, Alberta, Canada

Royal Columbian Hospital

New Westminster, British Columbia, Canada

St. Paul's Hospital, Providence Health Care

Vancouver, British Columbia, Canada

Victoria General Hospital

Victora, British Columbia, Canada

Royal Jubilee Hospital Victoria general Hospital

Victoria, British Columbia, Canada

Moncton Hospital

Moncton, New Brunswick, Canada

LHSC - University Hospital; Research Pharmacy

London, Ontario, Canada

Lakeridge Health

Oshawa, Ontario, Canada

Ottawa Hospital Research Institute

Ottawa, Ontario, Canada

The Ottawa Hospital - Civic Campus

Ottawa, Ontario, Canada

Toronto East General

Toronto, Ontario, Canada

University Health Network

Toronto, Ontario, Canada

Toronto Western Hospital

Toronto, Ontario, Canada

Centre Hospitalier de la Universite Laval

Québec, Quebec, Canada

Pavillion Chul-Chuq

Sainte-Foy, Quebec, Canada

Centre de santé et de services sociaux de Trois-Rivières

Trois-Rivières, Quebec, Canada

Hospital Dr. Hernan Henriquez Aravena

Temuco, , Chile

Clinica Renaca

Viña del Mar, , Chile

The University Hospital Brno

Brno, , Czechia

Fakultni nemocnice Hradec Kralove

Hradec Králové, , Czechia

Anesthesia and Intensive Care Dept., Regional Hospital Liberec

Liberec, , Czechia

University hospital Ostrava, Clinic of infectious medicine

Ostrava, , Czechia

Fakultni nemocnice Kralovske Vinohrady, Klinika anesteziologie a resuscitace

Prague, , Czechia

CH Victor Dupouy

Argenteuil, , France

Centre Hospitalier Universitaire de Clermont Ferrand

Clermont-Ferrand, , France

Service de Réanimation médicale - Bocage Central

Dijon, , France

APHP Raymond Poincare

Garches, , France

CHD Vendée

La Roche-sur-Yon, , France

CHRU Lille

Lille, , France

Réanimation Polyvalente, CHU Limoges

Limoges, , France

CHRU Nancy

Nancy, , France

Archet 1 university Hospital

Nice, , France

HOPITAL COCHIN university hospital

Paris, , France

Réanimation médicale NHC

Strasbourg, , France

Hopital Universitaire Hautepierre

Strasbourg, , France

Service de réanimation médicale, Hôpital Bretonneau

Tours, , France

Uniklinik Köln, Medizinischen Klinik I

Cologne, , Germany

Universitätsklinikum Frankfurt Goethe Universität

Frankfurt, , Germany

Universitätsklinikum Heidelberg

Heidelberg, , Germany

Uniklinikum Mainz

Mainz, , Germany

Uniklinik Tübingen

Tübingen, , Germany

University of Hong Kong

Hong Kong, , Hong Kong

Pest Megyei Flor Ferenc Korhaz

Kistarcsa, , Hungary

Jávorszky Ödön Hospital

Vác, , Hungary

Csolnoky Ferenc Kórház

Veszprém, , Hungary

Zala County Hospital ICU

Zalaegerszeg, , Hungary

Haemek Medical Center

Afula, , Israel

Soroka University Medical Centre

Beersheba, , Israel

Wolfson Medical Center

Holon, , Israel

Hadasit Medical Research Services and Development Ltd

Jerusalem, , Israel

Galilee Medical Center

Nahariya, , Israel

Nazareth EMMS Hospital

Nazareth, , Israel

Rabin Medical Center

Petah Tikva, , Israel

Kaplan Medical Center

Rehovot, , Israel

Ziv Medical Center

Safed, , Israel

Tel-Aviv Sourasky Medical Center

Tel Aviv, , Israel

Chaim Sheba Medical Center

Tel Litwinsky, , Israel

University Division of Infective and Tropical Diseases, University of Brescia, Italy

Brescia, Basilicate, Italy

Clinic of Infectious Diseases

Bologna, Emilia-Romagna, Italy

University Hospital Modena, Intensive Care Unit

Modena, Emilia-Romagna, Italy

National Institute for Infectious Diseases "L. Spallanzani"

Rome, Lazio, Italy

Asst Di Cremona

Cremona, Lombardy, Italy

Ospedale San Raffaele - Milano

Milan, Lombardy, Italy

A.O.U. S. Giovanni di Dio e Ruggi d'Aragona

Salerno, Sardinia, Italy

Hospital Civil de Guadalajara Dr Juan I Menchaca

Guadalajara, , Mexico

Hospital Civil de Guadalajara Fray Antonio Alcalde

Guadalajara, , Mexico

Instituto Nacional de Ciencias; Medicas y Nutricion; Salvador Zubiran

Mexico City, , Mexico

CEPREP; Hospital Universitario

Monterrey, , Mexico

Hospital General de Tijuana

Tijuana, , Mexico

Centro de Especialidades Medicas Del Estado de Veracruz Dr Rafael Lucio

Xalapa, , Mexico

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, , Netherlands

Gelre Ziekenhuizen Apeldoorn; Hospitals Pharmacy

Apeldoorn, , Netherlands

LUMC

Leiden, , Netherlands

UMC Radboud Nijmegen

Nijmegen, , Netherlands

Erasmus Medical Centre; Department of Virology L-359

Rotterdam, , Netherlands

Ikazia Hospital

Rotterdam, , Netherlands

UMCU

Utrecht, , Netherlands

Isala

Zwolle, , Netherlands

Auckland City Hospital

Auckland, , New Zealand

Christchurch Hospital

Christchurch, , New Zealand

Tauranga Hospital

Tauranga, , New Zealand

Hospital Regional del Cusco

Cusco, , Peru

Hospital Nacional Adolfo Guevara Velasco

Cuzco, , Peru

Hospital Guillermo Almenara Irigoyen Hospital Guillermo Almenara Irigoyen Hospital Guillermo Almen

La Victoria, , Peru

Clinica Internacional Sede Lima

Lima, , Peru

Hospital Nacional; Arzobispo Loayza

Lima, , Peru

Hospital Nacional Hipolito; Unanue

Lima, , Peru

Hospital Central Fuerza; Aerea del Peru

Lima, , Peru

Hospital Maria Auxiliadora

Lima, , Peru

Clínica San Gabriel

Lima, , Peru

Clinica San Borja

Lima, , Peru

Hospital de la Amistad Peru Corea II-2 Santa Rosa

Piura, , Peru

Clinica Divino Nino Jesus; Orden de Malta

San Juán de Miraflores, , Peru

Clinica Peruana Americana

Trujillo, , Peru

Oddział Anestezjologii i Intensywnej Terapii Wojewódzki Specjalistyczny Szpital im dr Wł Biegańsk

Lodz, , Poland

Wojewodzki Szpital Specjalistyczny

Lublin, , Poland

Icu Spsk - 2

Szczecin, , Poland

Oddział Anestezjologii i Intensywnej Terapii;Wojewódzki Szpital Zespolony im. L. Rydygiera

Torun, , Poland

Municipal Clinical Hospital #8

Chelyabinsk, , Russia

Municipal Healthcare Institution "City Hospital №2"

Engel's, , Russia

Medical Military Academy n.a S.M.Kirov

Saint Petersburg, , Russia

Paciific state medical university

Vladivostok, , Russia

Milpark Hospital

Parktown West, , South Africa

Emmed Research

Pretoria, , South Africa

Clinical Projects Research

Worcester, , South Africa

Pusan National University Hospital

Busan, , South Korea

Gachon University Gil Hospital

Incheon, , South Korea

Korea University Anam Hospital

Seoul, , South Korea

Korea University Guro Hospital

Seoul, , South Korea

Yonsei University Health System/Severance Hospital

Seoul, , South Korea

Hallym university Kangnam Sacred Heart Hospital; Infectious devision

Seoul, , South Korea

Wonju Severance Christian Hospital

Wŏnju, , South Korea

Hospital Universitario Son Espases

Palma de Mallorca, Balearic Islands, Spain

Mutua de Terrassa

Terrassa, Barcelona, Spain

Hospital Clinic

Barcelona, Cantabria, Spain

Hospital de Mataro

Mataro, Cantabria, Spain

Hospital Universitario Marques de Valdecilla

Santander, Cantabria, Spain

Hospital del Mar

Barcelona, , Spain

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Bellvitge University Hospital

Barcelona, , Spain

Hospital Universitario San Cecilio

Granada, , Spain

Hosp. Clinico San Carlos

Madrid, , Spain

Hospital Univ. de Getafe.Servicio de Neurologia

Madrid, , Spain

Joan XXIII University Hospital

Tarragona, , Spain

Servicio de Medicina Intensiva Hospital Universitario la Fe

Valencia, , Spain

Sahlgrenska Universitetssjukhuset

Gothenburg, , Sweden

Uppsala University Hospital, Department of Infectious Diseases

Gothenburg, , Sweden

Skånes Universitetssjukhus

Mamö, , Sweden

Norrland Universitetssjukhus

Umeå, , Sweden

Kaohsiung Medical University Hospital, Cancer Center

Kaohsiung City, , Taiwan

Far East Memorial Hospital

New Taipei City, , Taiwan

Wanfang Hospital

Taipei, , Taiwan

Chang Gung Medical Foundation Linkou Branch

Taoyuan, , Taiwan

Kyiv City Clinical Hospital #4

Kyiv, , Ukraine

Kyiv City Clinical Hospital #9

Kyiv, , Ukraine

Municipal Institution City Clinical Infectious Diseases Hospital

Odesa, , Ukraine

Poltava Regional Clinical Infectious Hospital

Poltava, , Ukraine

Municipal Institution Central City Hospital #1 City of Zhytomyr

Zhytomyr, , Ukraine

Queen Elizabeth Hospital

Birmingham, , United Kingdom

Heart of England NHS Trust

Birmingham, , United Kingdom

Queen Elizabeth University Hospital

Glasgow, , United Kingdom

Leeds General Infirmary, Anaesthetic Department, D Floor

Leeds, , United Kingdom

King College Hospital NHS Foundation Trust

London, , United Kingdom

University College London Hospitals NHS Foundation Trust - University College Hospital

London, , United Kingdom

Southampton University Hospitals NHS Trust

Southampton, , United Kingdom

University Hospitals of North Midlands NHS Trust-Royal Stoke University Hospital

Stoke-on-Trent, , United Kingdom

Taunton and Somerset NHS Foundation Trust Musgrove Park Hospital

Taunton, , United Kingdom

Countries

Belgium; Brazil; Bulgaria; Canada; Chile; Czechia; France; Germany; Hong Kong; Hungary; Israel; Italy; Mexico; Netherlands; New Zealand; Peru; Poland; Russia; South Africa; South Korea; Spain; Sweden; Taiwan; Ukraine; United Kingdom

References

Lim JJ, Nilsson AC, Silverman M, Assy N, Kulkarni P, McBride JM, Deng R, Li C, Yang X, Nguyen A, Horn P, Maia M, Castro A, Peck MC, Galanter J, Chu T, Newton EM, Tavel JA. A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial of MHAA4549A, a Monoclonal Antibody, plus Oseltamivir in Patients Hospitalized with Severe Influenza A Virus Infection. Antimicrob Agents Chemother. 2020 Jun 23;64(7):e00352-20. doi: 10.1128/AAC.00352-20. Print 2020 Jun 23.

Reference Type: DERIVED

PMID: 32393496 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2014-000461-43

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GV29216

Identifier Type: -

Identifier Source: org_study_id