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

Purpose

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.

Condition	Intervention	Phase
Asthma	Drug: Lebrikizumab Drug: Placebo	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Participant, Investigator Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Steroids

U.S. FDA Resources

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:

Relative Change From Baseline in Daily OCS Dose at Week 44 [ Time Frame: Baseline, Week 44 ]

Secondary Outcome Measures:

Absolute Change From Baseline in Daily OCS Dose at Week 44 [ Time Frame: Baseline, Week 44 ]
Relative Change From Week 12 in Average OCS Dose at Week 44 [ Time Frame: 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 [ Time Frame: Baseline, Week 44 ]
Percentage of Participants Discontinuing OCS Therapy or Having Achieved an Adrenal Maintenance Dose at Week 44 [ Time Frame: 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.
Percentage of Participants With Asthma Exacerbations [ Time Frame: Baseline up to Week 44 ]
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.
Percentage of Participants With Adverse Events [ Time Frame: Baseline up to 24 weeks after last dose administration (up to a minimum of approximately 2 years) ]
Percentage of Participants With Anti-therapeutic Antibodies (ATAs) Against Lebrikizumab [ Time Frame: 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) ]
Minimum Observed Serum Lebrikizumab Concentration (Cmin) [ Time Frame: Predose (0 hours) at Weeks 4, 12, 24, 36, and 44 ]


Enrollment:	230
Actual Study Start Date:	February 28, 2014
Study Completion Date:	December 20, 2016
Primary Completion Date:	December 20, 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Lebrikizumab High Dose 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 will be administered as SC injections every 4 weeks at dose and schedule described in arm description. Other Name: RO5490255
Experimental: Lebrikizumab Low Dose 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 Lebrikizumab will be administered as SC injections every 4 weeks at dose and schedule described in arm description. Other Name: RO5490255
Placebo Comparator: Placebo 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 Lebrikizumab will be administered as SC injections every 4 weeks at dose and schedule described in arm description. Other Name: RO5490255 Drug: Placebo Placebo matching to lebrikizumab will be administered as SC injections every 4 weeks as per schedule described in arm description.

Eligibility


Ages Eligible for Study:	12 Years to 75 Years (Child, Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01987492

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Sponsors and Collaborators

Hoffmann-La Roche

Investigators


Study Director:	Clinical Trials	Hoffmann-La Roche

More Information


Responsible Party:	Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT01987492 History of Changes
Other Study ID Numbers:	WB28182 2012-000190-24 ( EudraCT Number )
Study First Received:	November 12, 2013
Last Updated:	May 19, 2017

Additional relevant MeSH terms:


Asthma Bronchial Diseases Respiratory Tract Diseases Lung Diseases, Obstructive Lung Diseases Respiratory Hypersensitivity	Hypersensitivity, Immediate Hypersensitivity Immune System Diseases Antibodies, Monoclonal Immunologic Factors Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 17, 2017