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

NCT01987492 | Completed Phase 2

• 2 other identifiers: WB281822012-000190-24
• Study Type: interventional
• Target: 230
• Locations: 15 countries
• Sites: 69

Brief 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.

Conditions

Asthma

Outcome Measures

Primary Outcomes (1)

• Relative Change From Baseline in Daily OCS Dose at Week 44

  Baseline, Week 44

Secondary Outcomes (8)

• Absolute Change From Baseline in Daily OCS Dose at Week 44

  Baseline, Week 44

• Relative Change From Week 12 in Average OCS Dose at Week 44

  Week 12, Week 44

• Percentage of Participants Achieving at Least a 50 percent (%) Reduction in Their Daily OCS Dose at Week 44 Relative to Baseline

  Baseline, Week 44

• Percentage of Participants Discontinuing OCS Therapy or Having Achieved an Adrenal Maintenance Dose at Week 44

  Week 44

• Percentage of Participants With Asthma Exacerbations

  Baseline up to Week 44

Study Arms (3)

Lebrikizumab High Dose

EXPERIMENTAL

Participants will receive lebrikizumab at high dose level as subcutaneous (SC) injection every 4 weeks during the 44-week DBPC period, followed by a 32-week ATE period, and during the LTE period.

Drug: Lebrikizumab

Lebrikizumab Low Dose

EXPERIMENTAL

Participants will receive lebrikizumab at low dose level as SC injection every 4 weeks during the 44-week DBPC period, followed by a 32-week ATE period, and during the LTE period.

Drug: Lebrikizumab

Placebo

PLACEBO COMPARATOR

Participants will receive placebo matching to lebrikizumab SC injection every 4 weeks during the 44-week DBPC period. Participants will then be randomized to receive either high- or low-dose lebrikizumab every 4 weeks during the 32-week ATE period and will continue same treatment in the LTE period.

Drug: Lebrikizumab; Drug: Placebo

Interventions

Lebrikizumab DRUG

Lebrikizumab will be administered as SC injections every 4 weeks at dose and schedule described in arm description.

Also known as: RO5490255

Lebrikizumab High Dose; Lebrikizumab Low Dose; Placebo

Placebo DRUG

Placebo matching to lebrikizumab will be administered as SC injections every 4 weeks as per schedule described in arm description.

Placebo

Eligibility Criteria

• Age: 12 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (71)

Kern Allergy Med Clinic, Inc.

Bakersfield, California, 93301, United States

Location

Allergy & Asthma Care Center of Southern California

Long Beach, California, 90808, United States

Location

South Florida Research Center, Inc.

Miami, Florida, 33135, United States

Location

Georgia Pollens

Albany, Georgia, 31707, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Allergy & Immunology

Tulsa, Oklahoma, 74136, United States

Location

Pioneer Research Solutions

Houston, Texas, 77008, United States

Location

Metroplex Pulmonology & Sleep Center

McKinney, Texas, 75069, United States

Location

Pulmonary Consultants PLLC

Tacoma, Washington, 98405, United States

Location

Princess Alexandra Hospital, Department of Respiratory and Sleep Medicine

Brisbane, Queensland, 4102, Australia

Location

Monash Medical Centre; Respiratory and Sleep Medicine

Clayton, Victoria, 3168, Australia

Location

Institute for Respiratory Health Inc

Nedlands, Western Australia, 6009, Australia

Location

Clin Univ de Bxl Hôpital Erasme

Brussels, 1070, Belgium

Location

Longartsenpraktijk

Genk, 3600, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

Inspiration Research Limited

Toronto, Ontario, M5T 3A9, Canada

Location

Hornmed

Brno, 618 00, Czechia

Location

Nemocnice Liberec; KNL a.s. - TRN

Liberec, 460 63, Czechia

Location

Nemocnice Nový Jičín

Nový Jičín, 741-01, Czechia

Location

Rokycanska nemocnice

Rokycany, 337 22, Czechia

Location

Gentofte Hospital, Klinik for Allergi

Hellerup, 2900, Denmark

Location

CHU de Grenoble - Hôpital André Michallon

Grenoble, 38043, France

Location

CH de Bicetre; Pneumologie

Le Kremlin-Bicêtre, 94275, France

Location

Hôpital de La Croix Rousse

Lyon, 69004, France

Location

Hôpital Arnaud de Villeneuve

Montpellier, 34295, France

Location

CHU Nantes - Hôpital Laennec; Service de Pneumologie

Nantes, 44093, France

Location

CHU de Nice

Nice, 06001, France

Location

Hopital Bichat Claude Bernard ; Service de Pneumologie

Paris, 75877, France

Location

CHU de Haut Leveque

Pessac, 33604, France

Location

Nouvel Hôpital Civil; Pôle de Pathologie Thoracique

Strabourg, 67091, France

Location

Instituto Jalisciense de Investigacion Clinica S.A. de C.V.

Guadalajara, 44100, Mexico

Location

Centro Investigacion Medico Biologica y Terapia Avanzada

Guadalajara, 44130, Mexico

Location

Centro Integral Médico SJR SC

Querétaro, 76800, Mexico

Location

Academisch Medisch Centrum; Afdeling Longziekten, F5-258

Amsterdam, 1105 AZ, Netherlands

Location

Spaarne Ziekenhuis Hoofddorp; Long Geneeskunde

Hoofddorp, 2134 TM, Netherlands

Location

Antonius Ziekenhuis; Dept of Lung Diseases

Nieuwegein, 3435 CM, Netherlands

Location

NZ Respiratory & Sleep Institute

Auckland, 1051, New Zealand

Location

Dunedin Hospital

Dunedin, New Zealand

Location

Clinical Trials Unit, Bay of Plenty District Health Board

Tauranga, 3143, New Zealand

Location

Medical Research Inst. of New Zealand; Respiratory

Wellington, New Zealand

Location

Specjalistyczny Osrodek Alergologiczno-Internistyczny ALL-MED

Krakow, 31-024, Poland

Location

Malopolskie Centrum Alergologii

Krakow, 31-624, Poland

Location

SPZOZ Uniwersytecki Szpital Kliniczny nr 1 im. Norberta Barlickiego Uniwersytetu Medycznego w Lodzi

Lodz, 90-153, Poland

Location

Specjalistyczna Poradnia Pulmonologiczna

Ostrów Wielkopolski, 63-400, Poland

Location

Niepubliczny Zaklad Opieki Zdrowotnej PROFILAKTYKA Wladyslaw Pierzchala

Ruda Śląska, 41-707, Poland

Location

Klinika Chorób Wewnetrznych i Alergologii MSW

Warsaw, 02-507, Poland

Location

EMC Instytut Medyczny SA; Przychodnia przy ulicy Łowieckiej

Wroclaw, 50-220, Poland

Location

San Juan Bautista School of Medicine-Clinical Research Unit

Caguas, 00725, Puerto Rico

Location

Advanced Medical Concepts, PSC

Cidra, 00739, Puerto Rico

Location

ZAPA JJ Sro

Levice, 934 01, Slovakia

Location

Plucna ambulancia

Spišská Nová Ves, 052 01, Slovakia

Location

University Clinic of Pulmonary and Allergic Diseases Golnik

Golnik, 4204, Slovenia

Location

Complejo Hospitalario Universitario de Santiago; Servicio de Neumología

Santiago de Compostela, La Coruña, 15706, Spain

Location

Hospital de la Santa Creu; i Sant Pau

Barcelona, 08025, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Clinico Universitario de Salamanca; Servicio de Neumologia

Salamanca, 37007, Spain

Location

Hospital Universitario Doctor Peset

Valencia, 46017, Spain

Location

Belfast City Hospital; Respiratory Department

Belfast, BT9 7AB, United Kingdom

Location

Heartlands Hospital; Respiratory Department

Birmingham, B9 5SS, United Kingdom

Location

Gartnavel General Hospital; Respiratory Department

Glasgow, G12 0YN, United Kingdom

Location

New Lister Buliding, Level 1; Clinical Research Facility

Glasgow, G31 2ER, United Kingdom

Location

Royal Hospital For Children

Glasgow, G51 4TF, United Kingdom

Location

Southampton General Hospital; Respiratory Department

Hampshire, SO16 6YD, United Kingdom

Location

Leicester Royal Infirmary NHS Trust

Leicester, LE1 5WW, United Kingdom

Location

Glenfield Hospital; Respiratory -Allergy Unit

Leicester, LE3 9QP, United Kingdom

Location

St Bartholomew's Hospital (Barts); Respiratory Department

London, EC1A 7BE, United Kingdom

Location

Royal Brompton Hospital; Respiratory Department

London, SW3 6NP, United Kingdom

Location

Wythenshawe Hospital; North West Lung Research Centre

Manchester, M23 9LT, United Kingdom

Location

Freeman Hospital; Respiratory Department

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Derriford Hospital; The Lind Research Department

Plymouth, PL6 8DH, United Kingdom

Location

Sheffield Clinical Research Facility; National Institute for Health Research

Sheffield, S10 2JF, United Kingdom

Location

MeSH Terms

Conditions

Asthma

Interventions

lebrikizumab

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2013
• First Posted: November 19, 2013
• Study Start: February 28, 2014
• Primary Completion: December 20, 2016
• Study Completion: December 20, 2016
• Last Updated: May 22, 2017

Record last verified: 2017-05

Locations

AU (3); SL (1); PR (2); CZ (4); NZ (4); US (9); GB (14); NL (3); BE (3); DK (1); FR (9); CA (1); ME (3); PL (7); ES (5)