A Study of Lebrikizumab in Participants With Uncontrolled Asthma Who Are on Inhaled Corticosteroids and a Second Controller Medication

Asthma Clinical Trial

Official title:

A Phase III, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Lebrikizumab in Patients With Uncontrolled Asthma Who Are on Inhaled Corticosteroids and a Second Controller Medication

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01867125
• Other study ID #: GB28688
• Secondary ID: 2013-000175-33
• Status: Completed
• Phase: Phase 3
• First received: May 29, 2013
• Last updated: May 18, 2017
• Start date: July 31, 2013
• Est. completion date: January 2, 2017

Study information

• Verified date: May 2017
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized, multicenter, double-blind, placebo-controlled, parallel-group study will evaluate the efficacy and safety of lebrikizumab in participants with asthma whose disease remains uncontrolled despite daily treatment with inhaled corticosteroid (ICS) therapy and at least one second controller medication. Participants will be randomized in 1:1:1 ratio to receive double-blind treatment with either lebrikizumab ("high" or "low") or placebo, administered subcutaneously (SC) every 4 weeks for 52 weeks, in addition to their standard-of-care therapy. This will be followed by a 52-week double-blind active treatment extension. During double-blind active treatment extension period, all participants will receive SC injection of lebrikizumab from Week 53 to Week 104. The anticipated time on study treatment is 104 weeks. After study treatment, all participants will complete a 20-week safety follow-up.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1081
• Est. completion date: January 2, 2017
• Est. primary completion date: January 2, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Asthma diagnosis for greater than equal to (>/=) 12 months prior to Visit 1

• Bronchodilator response at Visit 1, 2, or 3

• Pre-bronchodilator FEV1 of 40 percent (%) - 80% predicted at both Visits 2 and 3

• On ICS therapy at a total daily dose of 500-2000 micrograms (mcg) of fluticasone propionate dry powder inhaler (DPI) or equivalent for >/=6 months prior to Visit 1

• On an eligible second controller medication (long-acting beta-agonist [LABA], leukotriene receptor antagonist [LTRA], long-acting muscarinic antagonist [LAMA], or theophylline) for 6 months prior to Visit 1

• Uncontrolled asthma at Visit 1 and/or Visit 2, and at Visit 3

• Chest X-ray or computed tomography (CT) scan within 3 months prior to Visit 1 or chest X-ray during the screening period (prior to Visit 3) confirming the absence of other clinically significant lung disease

• Demonstrated adherence with controller medication during the screening period

Exclusion Criteria:

• History of severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the lebrikizumab injection

• Maintenance oral corticosteroid therapy within 3 months of Visit 1

• Treatment with systemic (oral, intravenous [IV], or intramuscular [IM]) corticosteroids within 4 weeks prior to Visit 1 or during the screening period

• Treatment with intra-articular corticosteroids within 4 weeks prior to Visit 1 or during the screening period or anticipated need for intra-articular corticosteroids during the course of the study

• Infection requiring hospital admission for >/=24 hours or requiring treatment with IV or IM antibiotics within 4 weeks prior to Visit 1 or during screening; Upper or lower respiratory tract infection within 4 weeks prior to Visit 1 or during screening; Active infection that required treatment with oral antibiotics within 2 weeks prior to Visit 1 or during screening; Active parasitic infection or Listeria monocytogenes infection within 6 months prior to Visit 1 or during screening

• Active tuberculosis requiring treatment within 12 months prior to Visit 1

• Known immunodeficiency, including, but not limited to, human immunodeficiency virus (HIV) infection

• Evidence of acute or chronic hepatitis or known liver cirrhosis

• History of interstitial lung disease, chronic obstructive pulmonary disease (COPD), or other clinically significant lung disease other than asthma

• Known current malignancy or current evaluation for potential malignancy

• Current smoker or former smoker with a history of greater than (>) 10 pack-years

• History of alcohol or drug abuse

• Past and/or current use of any anti-interleukin (IL)-13 or anti-IL-4/IL-13 therapy, including lebrikizumab

• Use of other monoclonal antibody therapy, including omalizumab, within 6 months or 5 drug half-lives prior to Visit 1 (whichever is longer) or during screening

• Initiation of or change in allergen immunotherapy within 3 months prior to Visit 1 or during screening

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Lebrikizumab
Lebrikizumab will be administered as SC injection at 125 or 37.5 mg every 4 weeks, for 104 weeks.
• Placebo
Lebrikizumab matching placebo will be administered as SC injection every 4 weeks for 52 weeks.

Locations

Country	Name	City	State
Argentina	Centro Médico Dra de Salvo	Buenos Aires
Argentina	Fundación Faicep	Buenos Aires
Argentina	Instituto Ave Pulmo	Mar Del Plata
Argentina	Centro Respiratorio Quilmes	Quilmes
Argentina	Investigaciones en Patologias Respiratorias	San Miguel de Tucuman
Australia	Box Hill Hospital; Eastern Clinical Research Unit	Box Hill	Victoria
Australia	St. Vincent's Hospital Melbourne	Fitzroy	South Australia
Australia	Western Hospital	Footscray	Victoria
Australia	Liverpool Hospital	Liverpool BC	New South Wales
Australia	The Lung Institute of Western Australia; Sir Charles Gairdner Hospital	Nedlands	Western Australia
Belgium	Cliniques Universitaires St-Luc	Bruxelles
Belgium	UZ Gent	Gent
Canada	Alberta Health Services	Calgary	Alberta
Canada	Dr. E. Amer	Mississauga	Ontario
Canada	Albion Finch Medical Centre	Toronto	Ontario
Canada	Inspiration Research Limited	Toronto	Ontario
Canada	Centre d'investigation Clinique Mauricie	Trois-Rivières	Quebec
Chile	Centro de Investigaciones Medicas Respiratorias	Santiago
Chile	Schonffeldt y Guerrero Limitada	Santiago
Chile	Hospital Carlos Van Buren	Valparaiso
Colombia	Fundacion Neumologica Colombiana	Bogota DC
Czechia	Alergopraktik s.r.o.	Jablonec Nad Nisou
Czechia	Interni A Pneumologicka Ambulance	Jindrichuv Hradec
Czechia	MephaCentrum, a.s.	Ostrava - Poruba
Czechia	Alergologie Teplice, s.r.o.	Teplice
France	Hopital Calmette; Pneumologie	Lille
France	Hopital Nord; CIC	Marseille
France	Hôpital Arnaud de Villeneuve	Montpellier
France	CHU Nantes - Hôpital Laennec; Service de Pneumologie	Nantes
France	Nouvel Hôpital Civil; Pôle de Pathologie Thoracique	Strabourg
Germany	Lungenarztpraxis Tegel	Berlin
Germany	Pneumologisches Zentrum Wiesloch	Wiesloch
Hungary	Kenezy Korhaz Rendelointezet	Debrecen
Hungary	Petz Aladar Megyei Oktato Korhaz	Gyor
Hungary	C.C.C. Hospital Chest Diseases	Szeged
Israel	Barzilai Medical Center; Pulmonary Inst.	Ashkelon
Israel	Lady Davis Carmel Medical Center; Cardiovascular Medicine	Haifa
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Meir Medical Center; Pulmonary Dept	Kfar Saba
Israel	Kaplan Medical Center	Rehovot
Italy	Fondazione Salvatore Maugeri. IRCCS - Divisione di Pneumologia	Cassano Murge (BA)	Puglia
Italy	University of Catanzaro	Catanzaro	Calabria
Italy	Azienda Ospedaliera di Padova	Padova	Veneto
Italy	Azienda Ospedaliero Universitaria di Parma	Parma	Emilia-Romagna
Italy	A.o. Universitaria Pisana; Dipartimento Cardio Toracico	Pisa	Toscana
Italy	Azienda Ospedaliero Universitaria Ospedali Riuniti Umberto I-G.M. Lancisi-G. Salesi Di Ancona	Torrette - Ancona	Marche
Japan	Tosei General Hospital; Respiratory and Allergy Medicine	Aichi
Japan	Ofuji Clinic	Amagasaki-shi
Japan	Kyushu Central Hospital	Fukuoka-shi
Japan	National Hospital Organization Mito Medical Center	Higashiibaraki-gun
Japan	Hiroshima University Hospital	Hiroshima
Japan	National Hospital Organization Asahikawa Medical Center	Hokkaido
Japan	Oji General Hospital	Hokkaido
Japan	Iwate Medical University Hospital	Iwate
Japan	Yokohama City Minato Red Cross Hospital	Kanagawa
Japan	National Hospital Organization Tokyo National Hospital	Kiyose-shi
Japan	Kochi Medical School Hospital	Kochi
Japan	Oki Clinic	Kodaira-shi
Japan	Takahashi Clinic	Kokubunji-shi
Japan	Dokkyo Medical University Koshigaya Hospital	Koshigaya-shi
Japan	Tono Chuo Clinic	Mizunami-shi
Japan	Nagaoka Red Cross Hospital	Nagaoka-shi
Japan	Niigata City General Hospital	Niigata-shi
Japan	Kinki-Chuo Chest Medical Center	Osaka
Japan	Osaka City University Hospital	Osaka
Japan	Touda Clinic	Osaka
Japan	Senzoku Kokyuuki and Allergy Clinic	Ota-ku
Japan	Japan Community Health Care Organization Hokkaido Hospital	Sapporo-shi
Japan	Fukuwa Clinic	Tokyo
Japan	Sano Toranomon Clinic	Tokyo
Japan	Showa University Hospital	Tokyo
Japan	Teikyo University Hospital	Tokyo
Japan	Tokyo Center Clinic; Internal Medicine	Tokyo
Japan	Sekino Hospital	Toshima
Japan	University of Fukui Hospital	Yoshida-gun
Korea, Republic of	Seoul National University Bundang Hospital	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	St. Paul's Hospital, The Catholic University of Korea, College of Medicine	Seoul
Korea, Republic of	Wonju Christian Hospital	Wonju
Mexico	Instituto Jalisciense de Investigacion Clinica S.A. de C.V.	Guadalajara
Mexico	Hospital Dr Angel Leaño universidad Autonoma de Guadalajara AC	Zapopan
New Zealand	NZ Respiratory & Sleep Institute	Auckland
New Zealand	Dunedin Hospital	Dunedin
New Zealand	RMC Medical Research Ltd	Dunedin
New Zealand	P3 Research	Tauranga
Poland	Centrum Medycyny Oddechowej Robert M. Mróz	Bialystok
Poland	Prywatna Praktyka Lekarska Gabinet Pediatryczno-Alergologiczny	Bialystok
Poland	Grazyna Pulka Specjalistyczny Osrodek ALL-MED	Krakow
Poland	Niepubliczny Zaklad Opieki Zdrowotnej Centrum Medyczne ProMiMed sp z o.o. sp.k.	Kraków
Poland	Specjalistyczne Centrum Medyczne NOWOMED	Kraków
Poland	Poradnia Pulmonologiczna dla Doroslych	Lódz
Poland	Centrum Alergologii Teresa Hofman	Poznan
Poland	SPZOZ Proszowice	Proszowice
Poland	Niepubliczny Specjalistyczny ZOZ Puls-Med s.c.	Skarzysko-Kamienna
Poland	Klinika Chorób Wewnetrznych i Alergologii MSW	Warszawa
Poland	Medica Pro Familia Sp. z o.o. S.K.A.	Warszawa
Poland	ALL-MED Specjalistyczna Opieka Medyczna	Wroclaw
Romania	Colentina Clinical Hospital	Bucharest
Romania	Prof.Dr.Octavian Fodor Emergency Clinical Hospital	Cluj-Napoca
Romania	Spitalul Clinic de Boli Infectioase si Pneumoftiziologie Victor Babes Craiova	Craiova
Romania	Dr. Victor Babes Pneumology and Infectious Diseases Clinical Hospital	Timisoara
Russian Federation	SIH Kemerovo Regional Clinical Hospital	Kemerovo
Russian Federation	Central Clinical Hospital #1 of RZhD JCS	Moscow
Russian Federation	Russian Uni of People'S Friendship, Med. Faculty; City Clinical Hospital No 64, Internal Diseases	Moscow
Russian Federation	Novosibirsk Municipal Clinical Hospital For Emergency Medicine #2	Novosibirsk
Russian Federation	Ryazan Regional Clinical Hosp	Ryazan
Russian Federation	St. George the Martyr City Hospital	Saint Petersburg
Russian Federation	St.-Petersburg SMU n. a. Academician I.P.Pavlov; Therapy Department	Saint-Petersburg
Russian Federation	Smolensk State Medical Academy	Smolensk
Russian Federation	City Outpatient Dept #94	St Petersburg
Russian Federation	SHI Ctr Occupational Pathology	St. Petersburg
Russian Federation	St-Petersburg Diagnostic Ctr#1; Pulmonology	St. Petersburg
Russian Federation	St. Petersburg State Budget Medical Institution Pokrovskaya City Hospital	St. Petersburg
Russian Federation	Tomsk Regional Clinical Hospital	Tomsk
Serbia	Clinical Center of Serbia	Belgrade
Serbia	Clinical Hospital Center ''Bezanijska Kosa''; Department of Pulmology	Belgrade
Serbia	Clinical Hospital Center Zvezdara	Belgrade
Slovakia	Alian s.r.o.	Bardejov
Slovakia	Tehelná Clinic, Inc; IMUNO-ALERGO, s. r.o.	Bratislava
Slovakia	Plucna ambulancia	Spisska Nova Ves
South Africa	Melomed Hospital Gatesville	Cape Town
South Africa	Uni of Cape Town Lung Inst.	Cape Town
South Africa	Vawda Z.Fa Practice	Durban
South Africa	Gatesville Medical Centre	Gatesville
South Africa	Deepak Lakha MBCHB Private Practice	Johannesburg
South Africa	Botho ke Bontle Health Services	Pretoria
South Africa	Dr Johannes Breedt; Emmed Research	Pretoria
Spain	Hospital de la Santa Creu; i Sant Pau	Barcelona
Spain	Hospital Germans Trias i Pujol	Barcelona
Spain	Hosp Univ Fundacion Alcorcon	Madrid
Spain	Hospital Virgen del Rocio	Sevilla
Spain	Hospital Universitario Doctor Peset	Valencia
Spain	Hospital Universitario Araba	Vitoria	Alava
Turkey	Atatürk Gögüs Hastaliklari ve Gögüs Cerrahisi Egitim ve Arastirma Hastanesi	Ankara
Turkey	Turgut Ozal Universitesi Tip Fakultesi Bestepe Hastanesi	Ankara
Turkey	Uludag University; Pulmonology and Allergy Department	Bursa
Turkey	Canakkale Onsekiz Mart Universitesi Tip Fakultesi Hastanesi	Canakkale
Turkey	Ege University Medical Faculty	Izmir
Turkey	Izmir Dr. Suat Seren Gogus Hastaliklari ve Cerrahisi Egitim ve Arastirma Hastanesi	Izmir
Turkey	Kirikkale Universitesi Tip Fakultesi Hastanesi	Kirikkale
Turkey	Mersin University Medical Faculty	Mersin
Ukraine	Public Institution City Clinical Hospital # 6 of Dnipropetrovsk Regional Board	Dnepropetrovsk
Ukraine	Educational Scientific Medical Centre of Donetsk National Medical University;	Donetsk
Ukraine	Regional Phthisiology and Pulmonology Center	Ivano-Frankivsk
Ukraine	City Clinical Hospital #27	Kharkiv
Ukraine	Medical and Sanitary Unit of OJSC "Kharkiv Tractor Plant n.a. Ordzhonikidze"; Department of Therapy	Kharkiv
Ukraine	Central Outpatient Hospital of Desnyansky District	Kyiv
Ukraine	Kyiv City Clinical Hospital #8	Kyiv
Ukraine	Municipal Institution of Kyiv Regional Council Kyiv Regional Clinical Hospital	Kyiv
Ukraine	Yanovskyy Inst of Phth. & Pulm; Clinical-functional	Kyiv
Ukraine	Danylo Halytskyy National Medical University; Lviv	Lviv
Ukraine	Small Business Private Enterprise Medical Centre Pulse	Vinnytsya
Ukraine	Municipal Institution of Health Care "Yevpatoriya City Hospital ?1	Yevpatoriya
Ukraine	SI Dept. Clin. Hospital of Zaporizhzhia-2 Railway Station of SE Prydniprovska Zaliznytsia	Zaporizhzhia
United Kingdom	St Peters Hospital	Chertsey
United Kingdom	Castle Hill Hospital; Respiratory Medicine	Cottingham
United Kingdom	Ninewells Hospital; Asthma and Allergy Research Group	Dundee
United Kingdom	St James University Hospital; Respiratory Department	Leeds
United Kingdom	University North Tees	Teesside
United States	Central PA Asth & Allergy Care; Research Division	Altoona	Pennsylvania
United States	Tekton Research Inc	Austin	Texas
United States	Bellingham Asthma, Allergy & Immunology	Bellingham	Washington
United States	TTS Research	Boerne	Texas
United States	IMMUNOe International Research Centers	Centennial	Colorado
United States	St. Francis Sleep; Allergy & Lung Institute	Clearwater	Florida
United States	Pharmaceutical Research & Consulting, Inc.	Dallas	Texas
United States	Southeastern Lung Care	Decatur	Georgia
United States	Creekside Medical Research	DeLand	Florida
United States	Allergy & Asthma Research Center of El Paso	El Paso	Texas
United States	Allergy & Asthma Research Grp	Eugene	Oregon
United States	O & O Alpan, LLC	Fairfax	Virginia
United States	Clinical Trial Connection	Flagstaff	Arizona
United States	Allianz Medical and Research Center	Fountain Valley	California
United States	Infusion Associates	Grand Rapids	Michigan
United States	ADAC Research PA	Greenville	South Carolina
United States	Clinical Research Partners, LLC	Henrico	Virginia
United States	Allergy & Asthma Center of NC	High Point	North Carolina
United States	Pioneer Research Solutions	Houston	Texas
United States	Iowa Clinical Research Corporation	Iowa City	Iowa
United States	Allergy & Asthma Associates	Las Vegas	Nevada
United States	Asthma Allergy Phys of RI	Lincoln	Rhode Island
United States	Allergy & Asthma Medical Group & Research Center, Pc	Long Beach	California
United States	Alliance Research LLC	Long Beach	California
United States	Allergy Medical Clinic	Los Angeles	California
United States	CA Allergy & Asthma Med Grp	Los Angeles	California
United States	Dean Clinic	Madison	Wisconsin
United States	Manassas Clinical Research Center	Manassas	Virginia
United States	Metroplex Pulmonology & Sleep Center	McKinney	Texas
United States	Clinical Research Inst. of Southern Oregon, Pc	Medford	Oregon
United States	South Florida Research Phase I-IV, Inc	Miami	Florida
United States	Suncoast Research Group LLC	Miami	Florida
United States	Laporte County Institute For Clinical Research	Michigan City	Indiana
United States	Montana Medical Research LLC	Missoula	Montana
United States	Allergy & Asthma Research of Nj, Inc	Mount Laurel	New Jersey
United States	North Bay Clinical Trials	Napa	California
United States	North Shore University Hosp	New Hyde Park	New York
United States	Northeast Medical Research Associates, Inc	North Dartmouth	Massachusetts
United States	Allergy & Asthma Care of FL; Clinical Research	Ocala	Florida
United States	Atlantic Research Center, LLC	Ocean City	New Jersey
United States	Cor Clinical Research	Oklahoma City	Oklahoma
United States	Lynn Health Science Institute	Oklahoma City	Oklahoma
United States	Heartland Clinical Research Inc.	Omaha	Nebraska
United States	Choc Psf, Amc	Orange	California
United States	Emerald Coast Research Associates	Panama City	Florida
United States	Asthma & Allergy Center, P.C.	Papillion	Nebraska
United States	Alabama Clinical Research Associates	Pell City	Alabama
United States	Asthma Allergy Pulm Associates	Philadelphia	Pennsylvania
United States	Allergy Associates Research Center	Portland	Oregon
United States	Advances in Medicine	Rancho Mirage	California
United States	Midwest Clinical Research LLC	Saint Louis	Missouri
United States	Washington Univ. School of Med	Saint Louis	Missouri
United States	Quality Assurance Research Ctr	San Antonio	Texas
United States	Allergy Assoc Medical Group	San Diego	California
United States	UCSF School of Medicine	San Francisco	California
United States	ASTHMA, Inc	Seattle	Washington
United States	Grand View Hospital; Clinical Research Department	Sellersville	Pennsylvania
United States	Princeton Center For Clinical Research	Skillman	New Jersey
United States	Spartanburg Medical Research	Spartanburg	South Carolina
United States	Marycliff Allergy Specialists	Spokane	Washington
United States	Bensch Research Associates	Stockton	California
United States	Allergy & Asthma Diagnostic; Treatment Center	Tallahassee	Florida
United States	Montefiore Medical Center	The Bronx	New York
United States	Asthma & Allergy Center	Toledo	Ohio
United States	Desert Sun Clinical Research LLC	Tucson	Arizona
United States	Waterbury Pulmonary Associates	Waterbury	Connecticut
United States	PMG Research of Wilmington	Wilmington	North Carolina
United States	Florida Pulmonary Research Institute, LLC	Winter Park	Florida
United States	Atlanta Allergy & Asthma Clini	Woodstock	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Canada,  Chile,  Colombia,  Czechia,  France,  Germany,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  New Zealand,  Poland,  Romania,  Russian Federation,  Serbia,  Slovakia,  South Africa,  Spain,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of Asthma Exacerbations During the 52-Week Placebo-Controlled Period		Baseline up to 52 weeks
Secondary	Absolute Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1)		Baseline, Week 52
Secondary	Time to First Asthma Exacerbation		Baseline up to 52 weeks
Secondary	Change From Baseline in Standardized Asthma Quality of Life Questionnaire (AQLQ) Score		Baseline, Week 52
Secondary	Change from Baseline In Asthma Rescue Medication (Number of Puffs or Nebulized Treatments)		Baseline, Week 52
Secondary	Rate of Urgent Asthma-Related Urgent Health Care Utilization		Baseline up to Week 52
Secondary	Percentage of Participants With Anti-Therapeutic Antibodies to Lebrikizumab		Baseline up to Week 124 (assessed at Baseline, Weeks 4, 12, 24, 36, 52, 64, 76, 92, 104, 112, and 124)
Secondary	Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score		Baseline, Week 52
Secondary	Percentage of Participants With Adverse Events		Baseline, Week 124
Secondary	Minimum Serum Concentration (Cmin) of Lebrikizumab		Predose (0 hour) on Weeks 4, 12, 24, 36, and 52