A Study of Lebrikizumab (RO5490255) in Participants With Severe Oral Corticosteroids (OCS) Dependent Asthma

Asthma Clinical Trial

Official title:

A Phase II, Randomized, Double-Blind, Placebo Controlled, Multicenter Trial to Assess the Oral Corticosteroid-Sparing Effect of Lebrikizumab in Patients With Severe Corticosteroid Dependent Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01987492
• Other study ID #: WB28182
• Secondary ID: 2012-000190-24
• Status: Completed
• Phase: Phase 2
• First received: November 12, 2013
• Last updated: May 19, 2017
• Start date: February 28, 2014
• Est. completion date: December 20, 2016

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 of lebrikizumab compared with placebo, as measured by the ability of participants to achieve lower daily doses of OCS, among those with severe corticosteroid-dependent asthma. Prednisone/prednisolone will be the OCS therapy prescribed. Participants will be randomized to receive lebrikizumab or matching placebo for 44 weeks in a double-blind, placebo-controlled (DBPC) period. Those who complete the 44-week period may continue into a 32-week active treatment extension (ATE) period, during which all participants will receive lebrikizumab treatment. Following completion of the ATE period, participants who have both tolerated and derived benefit from treatment with lebrikizumab may continue their lebrikizumab treatment into a long-term extension (LTE) period. Participants will transition to 24 weeks of safety follow-up upon discontinuation of study drug.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 230
• Est. completion date: December 20, 2016
• Est. primary completion date: December 20, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 75 Years

Eligibility

Inclusion Criteria:

• Severe asthma despite intensive follow-up by an asthma specialist for >/=6 months prior to Visit 1

• Baseline forced expiratory volume in 1 second (FEV1) >/=40% of predicted prior to randomization

• Receiving high doses of inhaled glucocorticosteroids at a total daily dose of >/=1500 micrograms (mcg) beclomethasone dipropionate or equivalent and long-acting beta-adrenoceptor agonist (LABA), with or without an additional controller, for at least 3 months prior to Visit 1

• Chronic treatment with maintenance OCS for >/=6 months prior to Visit 1

• Assessment to ensure diagnosis of refractory asthma and OCS dependence on minimal effective or maximum tolerated dose prior to Visit 1 with compliance

Exclusion Criteria:

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

• Asthma exacerbation within 28 days prior to Visit 1 or during screening (prior to Visit 3)

• For adults: Active tuberculosis requiring treatment within the 12 months prior to Visit 1

• For adolescents: History of active tuberculosis requiring treatment

• Evidence of acute or chronic hepatitis or known liver cirrhosis

• Known current malignancy or current evaluation for a potential malignancy

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

• Infection requiring hospital admission or requiring treatment with intravenous (IV) or intramuscular (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 parasitic infection or Listeria monocytogenes infection within 6 months prior to Visit 1 or during screening

• Current smoker or former smoker with a smoking history of more than 15 pack-years

• Current use of an immunomodulatory/ immunosuppressive therapy or past use within 3 months or 5 drug half-lives (whichever is longer) prior to Visit 1

• Use of a licensed or investigational monoclonal antibody other than anti-interleukin (IL)-13 or anti-IL-4/IL-13, including but not limited to, omalizumab, anti-IL-5, or anti-IL-17, within 6 months or 5 drug half-lives (whichever is longer) prior to Visit 1

• Receipt of a live attenuated vaccine within the 4 weeks prior to Visit 1 during screening or anticipation of receipt of a live attenuated vaccine throughout the study

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Lebrikizumab
Lebrikizumab will be administered as SC injections every 4 weeks at dose and schedule described in arm description.
• Placebo
Placebo matching to lebrikizumab will be administered as SC injections every 4 weeks as per schedule described in arm description.

Locations

Country	Name	City	State
Australia	Princess Alexandra Hospital, Department of Respiratory and Sleep Medicine	Brisbane	Queensland
Australia	Monash Medical Centre; Respiratory and Sleep Medicine	Clayton	Victoria
Australia	Institute for Respiratory Health Inc	Nedlands	Western Australia
Belgium	Clin Univ de Bxl Hôpital Erasme	Bruxelles
Belgium	Longartsenpraktijk	Genk
Belgium	UZ Gent	Gent
Canada	Inspiration Research Limited	Toronto	Ontario
Czechia	Hornmed	Brno
Czechia	Nemocnice Liberec; KNL a.s. - TRN	Liberec 1
Czechia	Nemocnice Nový Jicín	Nový Jicín
Czechia	Rokycanska nemocnice	Rokycany
Denmark	Gentofte Hospital, Klinik for Allergi	Hellerup
France	CHU de Grenoble - Hôpital André Michallon	Grenoble Cedex 9
France	CH de Bicetre; Pneumologie	Le Kremlin Bicetre
France	Hôpital de La Croix Rousse	Lyon
France	Hôpital Arnaud de Villeneuve	Montpellier
France	CHU Nantes - Hôpital Laennec; Service de Pneumologie	Nantes
France	CHU de Nice	Nice Cedex 1
France	Hopital Bichat Claude Bernard ; Service de Pneumologie	Paris
France	CHU de Haut Leveque	Pessac
France	Nouvel Hôpital Civil; Pôle de Pathologie Thoracique	Strabourg
Mexico	Centro Investigacion Medico Biologica y Terapia Avanzada	Guadalajara
Mexico	Instituto Jalisciense de Investigacion Clinica S.A. de C.V.	Guadalajara
Mexico	Centro Integral Médico SJR SC	Querétaro
Netherlands	Academisch Medisch Centrum; Afdeling Longziekten, F5-258	Amsterdam
Netherlands	Spaarne Ziekenhuis Hoofddorp; Long Geneeskunde	Hoofddorp
Netherlands	Antonius Ziekenhuis; Dept of Lung Diseases	Nieuwegein
New Zealand	NZ Respiratory & Sleep Institute	Auckland
New Zealand	Dunedin Hospital	Dunedin
New Zealand	Clinical Trials Unit, Bay of Plenty District Health Board	Tauranga
New Zealand	Medical Research Inst. of New Zealand; Respiratory	Wellington
Poland	Malopolskie Centrum Alergologii	Krakow
Poland	Specjalistyczny Osrodek Alergologiczno-Internistyczny ALL-MED	Krakow
Poland	SPZOZ Uniwersytecki Szpital Kliniczny nr 1 im. Norberta Barlickiego Uniwersytetu Medycznego w Lodzi	Lodz
Poland	Specjalistyczna Poradnia Pulmonologiczna	Ostrow Wielkopolski
Poland	Niepubliczny Zaklad Opieki Zdrowotnej PROFILAKTYKA Wladyslaw Pierzchala	Ruda Slaska
Poland	Klinika Chorób Wewnetrznych i Alergologii MSW	Warszawa
Poland	EMC Instytut Medyczny SA; Przychodnia przy ulicy Lowieckiej	Wroclaw
Puerto Rico	San Juan Bautista School of Medicine-Clinical Research Unit	Caguas
Puerto Rico	Advanced Medical Concepts, PSC	Cidra
Slovakia	ZAPA JJ Sro	Levice
Slovakia	Plucna ambulancia	Spisska Nova Ves
Slovenia	University Clinic of Pulmonary and Allergic Diseases Golnik	Golnik
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital de la Santa Creu; i Sant Pau	Barcelona
Spain	Hospital Clinico Universitario de Salamanca; Servicio de Neumologia	Salamanca
Spain	Complejo Hospitalario Universitario de Santiago; Servicio de Neumología	Santiago de Compostela	La Coruña
Spain	Hospital Universitario Doctor Peset	Valencia
United Kingdom	Belfast City Hospital; Respiratory Department	Belfast
United Kingdom	Heartlands Hospital; Respiratory Department	Birmingham
United Kingdom	Gartnavel General Hospital; Respiratory Department	Glasgow
United Kingdom	New Lister Buliding, Level 1; Clinical Research Facility	Glasgow
United Kingdom	Royal Hospital For Children	Glasgow
United Kingdom	Southampton General Hospital; Respiratory Department	Hampshire
United Kingdom	Glenfield Hospital; Respiratory -Allergy Unit	Leicester
United Kingdom	Leicester Royal Infirmary NHS Trust	Leicester
United Kingdom	Royal Brompton Hospital; Respiratory Department	London
United Kingdom	St Bartholomew's Hospital (Barts); Respiratory Department	London
United Kingdom	Wythenshawe Hospital; North West Lung Research Centre	Manchester
United Kingdom	Freeman Hospital; Respiratory Department	Newcastle upon Tyne
United Kingdom	Derriford Hospital; The Lind Research Department	Plymouth
United Kingdom	Sheffield Clinical Research Facility; National Institute for Health Research	Sheffield
United States	Georgia Pollens	Albany	Georgia
United States	Kern Allergy Med Clinic, Inc.	Bakersfield	California
United States	Pioneer Research Solutions	Houston	Texas
United States	Allergy & Asthma Care Center of Southern California	Long Beach	California
United States	Metroplex Pulmonology & Sleep Center	McKinney	Texas
United States	South Florida Research Center, Inc.	Miami	Florida
United States	Mount Sinai Medical Center	New York	New York
United States	Pulmonary Consultants PLLC	Tacoma	Washington
United States	Allergy & Immunology	Tulsa	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Czechia,  Denmark,  France,  Mexico,  Netherlands,  New Zealand,  Poland,  Puerto Rico,  Slovakia,  Slovenia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Relative Change From Baseline in Daily OCS Dose at Week 44		Baseline, Week 44
Secondary	Absolute Change From Baseline in Daily OCS Dose at Week 44		Baseline, Week 44
Secondary	Relative Change From Week 12 in Average OCS Dose at Week 44		Week 12, Week 44
Secondary	Percentage of Participants Achieving at Least a 50 percent (%) Reduction in Their Daily OCS Dose at Week 44 Relative to Baseline		Baseline, Week 44
Secondary	Percentage of Participants Discontinuing OCS Therapy or Having Achieved an Adrenal Maintenance Dose at Week 44	Percentage of participants discontinuing OCS therapy or having achieved adrenal maintenance dose (cortisol level less than or equal to 100 nanomoles per liter) will be reported.	Week 44
Secondary	Percentage of Participants With Asthma Exacerbations	An asthma exacerbation is defined as new or increased asthma symptoms (including wheeze, cough, dyspnea, chest tightness, or nocturnal awakenings due to these symptoms) that lead to treatment with systemic corticosteroids greater than or equal to (>/=) 30 milligrams (mg) or 0.5 mg per kilogram (kg) for >/=3 consecutive days or to hospitalization.	Baseline up to Week 44
Secondary	Percentage of Participants With Adverse Events		Baseline up to 24 weeks after last dose administration (up to a minimum of approximately 2 years)
Secondary	Percentage of Participants With Anti-therapeutic Antibodies (ATAs) Against Lebrikizumab		Predose (0 hours) at Weeks 0, 4, 12, 24, 36, 44, 52, 64, and 76, at early discontinuation (up to a minimum of approximately 2 years), and at 24 weeks after last dose administration (up to a minimum of approximately 2 years)
Secondary	Minimum Observed Serum Lebrikizumab Concentration (Cmin)		Predose (0 hours) at Weeks 4, 12, 24, 36, and 44