Clinical Trial Results:
A Phase III, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Lebrikizumab in Adult Patients with Mild-to-Moderate Asthma
Summary
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EudraCT number |
2013-004625-81 |
Trial protocol |
CZ BG GB SK |
Global end of trial date |
22 Jan 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
30 Mar 2017
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First version publication date |
30 Mar 2017
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
WA29249
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02104674 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
F. Hoffmann-La Roche AG
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Sponsor organisation address |
Grenzacherstrasse 124, Basel, Switzerland, CH-4070
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Public contact |
F.Hoffmann-La Roche Ltd., Roche Trial Information Hotline, 41 616878333, global.trial_information@roche.com
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Scientific contact |
F.Hoffmann-La Roche Ltd., Roche Trial Information Hotline, 41 616878333, global.trial_information@roche.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
18 Mar 2016
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
22 Jan 2016
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
A Phase III, randomized, double-blind, placebo-controlled study to evaluate the efficacy of lebrikizumab compared with placebo in improving lung function in adult participants with mild-to-moderate asthma.
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Protection of trial subjects |
The study was conducted in accordance with the principles of the Declaration of Helsinki, International Conference on Harmonisation (ICH) E6 guideline for Good Clinical Practice (GCP) and investigators were trained according to applicable Sponsor standard operating procedures (SOPs). Roche and the investigators strictly adhered to the stated provisions in these guidelines. This was documented by the investigator’s signature on the protocol agreeing to carry out all of its terms in accordance with the applicable regulations and law and to follow ICH GCP guidelines for good clinical practice.
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Background therapy |
Participants could only receive short-acting beta agonists (SABA) therapy for asthma treatment at study entry (less than [<] 10 puffs daily). | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
07 Jun 2014
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
2 Months | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Poland: 36
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Country: Number of subjects enrolled |
Romania: 14
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Country: Number of subjects enrolled |
United Kingdom: 3
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Country: Number of subjects enrolled |
Bulgaria: 33
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Country: Number of subjects enrolled |
Czech Republic: 9
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Country: Number of subjects enrolled |
United States: 138
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Country: Number of subjects enrolled |
Brazil: 10
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Country: Number of subjects enrolled |
Canada: 9
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Country: Number of subjects enrolled |
New Zealand: 7
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Country: Number of subjects enrolled |
Russian Federation: 23
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Country: Number of subjects enrolled |
South Africa: 31
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Worldwide total number of subjects |
313
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EEA total number of subjects |
95
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
293
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From 65 to 84 years |
20
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
Out of 313 enrolled participants, 3 were randomized but not treated during a 12-week treatment period where participants received blinded lebrikizumab/placebo or an open-label active comparator (Montelukast sodium). | ||||||||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | ||||||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Lebrikizumab | ||||||||||||||||||||||||||||||||||||
Arm description |
Lebrikizumab 125 milligrams (mg) administered as subcutaneous (SC) injection on Day 1, 29, and 57 during the 12-week treatment period. | ||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Lebrikuzimab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection in pre-filled injector
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Lebrikizumab administered as SC injection during the 12-week treatment period.
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Arm title
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Montelukast | ||||||||||||||||||||||||||||||||||||
Arm description |
Montelukast 10 mg tablet administered orally once daily during the 12-week treatment period. | ||||||||||||||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Montelukast
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Investigational medicinal product code |
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Other name |
Singulair
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Montelukast administered orally during the 12-week treatment period.
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Arm title
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Placebo | ||||||||||||||||||||||||||||||||||||
Arm description |
Placebo matched to Lebrikuzimab as SC injection administered on Day 1, 29, and 57 during the 12-week treatment period. | ||||||||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection in pre-filled injector
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Placebo matched to Lebrikuzimab as SC injection administered during the 12-week treatment period.
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Baseline characteristics reporting groups
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Reporting group title |
Lebrikizumab
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Reporting group description |
Lebrikizumab 125 milligrams (mg) administered as subcutaneous (SC) injection on Day 1, 29, and 57 during the 12-week treatment period. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Montelukast
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Reporting group description |
Montelukast 10 mg tablet administered orally once daily during the 12-week treatment period. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Placebo matched to Lebrikuzimab as SC injection administered on Day 1, 29, and 57 during the 12-week treatment period. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Lebrikizumab
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Reporting group description |
Lebrikizumab 125 milligrams (mg) administered as subcutaneous (SC) injection on Day 1, 29, and 57 during the 12-week treatment period. | ||
Reporting group title |
Montelukast
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Reporting group description |
Montelukast 10 mg tablet administered orally once daily during the 12-week treatment period. | ||
Reporting group title |
Placebo
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Reporting group description |
Placebo matched to Lebrikuzimab as SC injection administered on Day 1, 29, and 57 during the 12-week treatment period. | ||
Subject analysis set title |
Lebrikizumab-Modified Intent to Treat (mITT)
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Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
Lebrikizumab 125 mg administered as SC injection on Day 1, 29 and 57 during the 12-week treatment period.
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Subject analysis set title |
Montelukast-mITT
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Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
Montelukast 10 mg tablet administered orally once daily during the 12-week treatment period.
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Subject analysis set title |
Placebo-mITT
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Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
Placebo matched to Lebrikuzimab administered as SC injection on Day 1, 29 and 57 during the 12-week treatment period.
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Subject analysis set title |
Montelukast-Safety
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Montelukast 10 mg tablet administered orally once daily during the 12 week treatment period. Participants were followed up further for 8 weeks during the safety follow-up period.
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Subject analysis set title |
Placebo-Safety
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Placebo matched to Lebrikuzimab administered as SC injection on Day 1, 29 and 57 during the 12-week treatment period. Participants were followed up further for 8 weeks during the safety follow-up period.
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Subject analysis set title |
Lebrikizumab-Safety
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Lebrikuzimab administered as SC injection on Day 1, 29 and 57 during the 12-week treatment period. Participants were followed up further for 8 weeks during the safety follow-up period.
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End point title |
Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Week 12 | ||||||||||||||||
End point description |
FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Modified intent to treat (mITT) population included all randomized participants who received at least one dose of study drug.
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End point type |
Primary
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End point timeframe |
Baseline, Week 12
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Statistical analysis title |
Statistical Analysis 1 | ||||||||||||||||
Statistical analysis description |
The model used absolute change from baseline in pre-bronchodilator in FEV1 as response and the following covariates: Baseline pre-bronchodilator in FEV1, Region, Treatment, Week, and a 4-level categorical variable using Periostin (PERI) and Eosonophil (EOS) levels as (PERI High/EOS High, PERI High/EOS Low, PERI Low/EOS High, and PERI Low/EOS Low)
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Comparison groups |
Lebrikizumab-Modified Intent to Treat (mITT) v Placebo-mITT
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Number of subjects included in analysis |
209
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.06 [1] | ||||||||||||||||
Method |
MMRM | ||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||
Point estimate |
0.08
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
2-sided
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lower limit |
0 | ||||||||||||||||
upper limit |
0.17 | ||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.044
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Notes [1] - Mixed effects model for repeated measures (MMRM) was used to model the absolute change from baseline. |
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Statistical analysis title |
Statistical Analysis 2 | ||||||||||||||||
Statistical analysis description |
The model used absolute change from baseline in pre-bronchodilator in FEV1 as response and the following covariates: Baseline pre-bronchodilator in FEV1, Region, Treatment, Week, and a 4-level categorical variable using PERI and EOS levels as (PERI High/EOS High, PERI High/EOS Low, PERI Low/EOS High, and PERI Low/EOS Low).
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Comparison groups |
Placebo-mITT v Montelukast-mITT
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Number of subjects included in analysis |
206
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||
P-value |
= 0.6954 [2] | ||||||||||||||||
Method |
MMRM | ||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||
Point estimate |
-0.02
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Confidence interval |
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level |
95% | ||||||||||||||||
sides |
2-sided
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lower limit |
-0.1 | ||||||||||||||||
upper limit |
0.07 | ||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.043
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Notes [2] - MMRM was used to model the absolute change from baseline. |
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End point title |
Change From Baseline in Asthma Reliever Medication use at Week 12 | ||||||||||||
End point description |
Participants could only receive SABA therapy for asthma treatment as asthma reliever medication (<10 puffs daily). SABA use was recorded in the eDiary. mITT population. Here, "Number of subjects analysed" indicates the total number of participants who provided evaluable data for this outcome measure.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 12
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Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Statistical analysis description |
MMRM was used to model the absolute change from baseline. The model used absolute change from baseline asthma reliever medication (ARM) as response and the following covariates: Baseline ARM, Region, Baseline % of predicted FEV1, Treatment, Week, and a 4-level categorical variable using PERI and EOS levels as (PERI High/EOS High, PERI High/EOS Low, PERI Low/EOS High, and PERI Low/EOS Low)
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Comparison groups |
Lebrikizumab-Modified Intent to Treat (mITT) v Placebo-mITT
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Number of subjects included in analysis |
203
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
Method |
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Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0.04
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.24 | ||||||||||||
upper limit |
0.32 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.144
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End point title |
Change From Baseline in the Standardized Asthma Quality of Life Questionnaire (AQLQ[S]) Overall Score at Week 12 | ||||||||||||
End point description |
The AQLQ[S]) was used to assess the participant’s asthma-specific health-related quality of life. The 32-item questionnaire contains four domains: activity limitations, symptoms, emotional function, and environmental stimuli. The AQLQ[S]) has a recall specification of 2 weeks. Participants were asked to think about how they had been during the previous 2 weeks and to respond to each of the 32 questions on a 7-point scale (7 = not impaired at all; 1 = severely impaired). An increase in the AQLQ score indicates a better quality of life. The overall AQLQ score is the mean of all 32 responses and the individual domain scores are the means of the items in those domains. mITT population. Here, "Number of subjects analysed" indicates the total number of participants who provided evaluable data for this outcome measure.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 12
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Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Statistical analysis description |
MMRM was used to model the absolute change from baseline. The model used absolute change from baseline AQLQ[S]) as response and the following covariates: Baseline AQLQ[S]), Region, Baseline % of predicted FEV1, Treatment, Week, and a 4-level categorical variable using PERI and EOS levels as (PERI High/EOS High, PERI High/EOS Low, PERI Low/EOS High, and PERI Low/EOS Low)
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Comparison groups |
Lebrikizumab-Modified Intent to Treat (mITT) v Placebo-mITT
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Number of subjects included in analysis |
204
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
Method |
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Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-0.06
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.29 | ||||||||||||
upper limit |
0.17 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.115
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End point title |
Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) Levels at Week 12 | ||||||||||||||||||||||||
End point description |
Safety population included all participants who received at least one dose of study drug and who were grouped according to the treatment they received. Here, number (n)= number of participants evaluable for the specified timepoints.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 12
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Blood Eosinophil Count at Week 12 | ||||||||||||||||||||||||
End point description |
Safety population. Here, number (n)= number of participants evaluable for the specified timepoints.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 12
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Serum Periostin at Week 12 | ||||||||||||||||||||||||
End point description |
Safety population. Here, number (n)= number of participants evaluable for the specified timepoints.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 12
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Total Immunoglobulin E (IgE) Levels at Week 12 | ||||||||||||||||||||||||
End point description |
Safety population. Here, "Number of subjects analysed" indicates the total number of participants who provided evaluable data for this outcome measure and number (n)= number of participants evaluable for the specified timepoints.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 12
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No statistical analyses for this end point |
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End point title |
Change From Baseline in C-C Motif Chemokine Ligand 13 (CCL-13) Levels at Week 12 | ||||||||||||||||||||||||
End point description |
Safety population. Here, "Number of subjects analysed" indicates the total number of participants who provided evaluable data for this outcome measure and number (n)= number of participants evaluable for the specified timepoints.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 12
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No statistical analyses for this end point |
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End point title |
Change From Baseline in CCL-17 Levels at Week 12 | ||||||||||||||||||||||||
End point description |
Safety population included all participants who received at least one dose of study drug and who were grouped according to the treatment they received. Here, "Number of subjects analysed" indicates the total number of participants who provided evaluable data for this outcome measure and number (n)= number of participants evaluable for the specified timepoints.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 12
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No statistical analyses for this end point |
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End point title |
Maximum Observed Plasma Lebrikizumab Concentration After the First Dose (Cmax) | ||||||||
End point description |
Pharmacokinetic (PK)-evaluable population included participants who had received at least one subcutaneous dose of lebrikizumab and had at least one lebrikizumab PK sample. Here, N (number of participants analyzed) indicates the total number of participants who provided evaluable data for this outcome measure.
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End point type |
Secondary
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End point timeframe |
Postdose on Day 8
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No statistical analyses for this end point |
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End point title |
Time to Reach Maximum Lebrikizumab Concentration After the First Dose (Tmax) | ||||||||
End point description |
PK-evaluable population. Here, N (number of participants analyzed) indicates the total number of participants who provided evaluable data for this outcome measure.
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End point type |
Secondary
|
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End point timeframe |
Postdose on Day 8
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Predose Serum Lebrikizumab Concentration (Cmin) at Week 4 | ||||||||
End point description |
PK-evaluable population. Here, "Number of subjects analysed" indicates the total number of participants who provided evaluable data for this outcome measure.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Predose (at Hour 0) on Week 4
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Predose Serum Lebrikizumab Concentration (Cmin) at Week 12 | ||||||||
End point description |
PK-evaluable population. Here, "Number of subjects analysed" indicates the total number of participants who provided evaluable data for this outcome measure.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Predose (at Hour 0) on Week 12
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||
End point title |
Plasma Elimination Half-Life (t1/2) of Lebrikizumab | ||||||||
End point description |
PK-evaluable population. Here, "Number of subjects analysed" indicates the total number of participants who provided evaluable data for this outcome measure.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Predose (at Hour 0) on Day 57, Days 85, 113, 141
|
||||||||
|
|||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change Fom Baseline in Morning Pre-bronchodilator Peak Expiratory Flow (PEF) at Week 12: Placebo Versus Montelukast | ||||||||||||
End point description |
PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. mITT population. Here, "Number of subjects analysed" indicates the total number of participants who provided evaluable data for this outcome measure.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Week 12
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Statistical analysis description |
MMRM was used to model the absolute change from baseline. The model used absolute change from baseline PEF as response and the following covariates: Baseline PEF, Region, Baseline % of predicted FEV1, Treatment, Week, and a 4-level categorical variable using PERI and EOS levels as (PERI High/EOS High, PERI High/EOS Low, PERI Low/EOS High,and PERI Low/EOS Low).
|
||||||||||||
Comparison groups |
Montelukast-mITT v Placebo-mITT
|
||||||||||||
Number of subjects included in analysis |
199
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
1.23
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-14.57 | ||||||||||||
upper limit |
17.04 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
8.012
|
|
|||||||||||||
End point title |
Change From Baseline in Morning Pre-bronchodilator PEF at Week 12: Placebo Versus Lebrikizumab | ||||||||||||
End point description |
PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. mITT population. Here, "Number of subjects analysed" indicates the total number of participants who provided evaluable data for this outcome measure.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Week 12
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Statistical analysis description |
MMRM was used to model the absolute change from baseline. The model used absolute change from baseline PEF as response and the following covariates: Baseline PEF, Region, Baseline % of predicted FEV1, Treatment, Week, and a 4-level categorical variable using PERI and EOS levels as (PERI High/EOS High, PERI High/EOS Low, PERI Low/EOS High, and PERI Low/EOS Low).
|
||||||||||||
Comparison groups |
Lebrikizumab-Modified Intent to Treat (mITT) v Placebo-mITT
|
||||||||||||
Number of subjects included in analysis |
203
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
Method |
|||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-3.61
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-18.46 | ||||||||||||
upper limit |
11.23 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
7.523
|
|
||||||||||
End point title |
Number of Participants With Treatment Failure | |||||||||
End point description |
Treatment failure was defined as a worsening of asthma symptoms (per investigator’s assessment of participant report) in association with either relative decline in pre-bronchodilator FEV1 >=20%; or >=20% decline in morning pre-bronchodilator PEF on 2 consecutive days compared with baseline; or use of >=10 puffs of albuterol metered dose inhaler (MDI); or >=2 additional administrations (or any new use) of nebulized short-acting β-agonist (SABA) therapy within any calendar day; or need for any inhaled, oral, or parenteral corticosteroid or for a controller medication. The hazard ratio from the Cox Proportional Hazards model compared the risk of treatment failure for the lebrikizumab-treated and placebo participants. mITT population.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Baseline up to Week 12
|
|||||||||
|
||||||||||
Statistical analysis title |
Statistical Analysis 1 | |||||||||
Statistical analysis description |
Multivariate Cox proportional hazards regression was used to estimate Hazard Ratios. Confidence intervals (CI) calculated according to Wald. Covariates: treatment, region, baseline periostin and eosinophil category, and baseline percentage FEV1 category.
|
|||||||||
Comparison groups |
Placebo-mITT v Lebrikizumab-Modified Intent to Treat (mITT)
|
|||||||||
Number of subjects included in analysis |
209
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
superiority | |||||||||
Method |
||||||||||
Parameter type |
Hazard ratio (HR) | |||||||||
Point estimate |
1.06
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
0.47 | |||||||||
upper limit |
2.42 |
|
|||||||||||||
End point title |
Time to Treatment Failure | ||||||||||||
End point description |
Treatment failure was defined as a worsening of asthma symptoms (per investigator’s assessment of participant report) in association with either relative decline in pre-bronchodilator FEV1 >=20%; or >=20% decline in morning pre-bronchodilator PEF on 2 consecutive days compared with baseline; or use of >=10 puffs of albuterol metered dose inhaler (MDI); or >=2 additional administrations (or any new use) of nebulized short-acting β-agonist (SABA) therapy within any calendar day; or need for any inhaled, oral, or parenteral corticosteroid or for a controller medication. Time to treatment failure was estimated using Kaplan-Meier method. mITT population. Median and corresponding 95% CI could not be estimated due to higher number (>50%) of censored participants who have been reported as 99999.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Basleine up to Week 12
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Baseline up to Week 20
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Safety population.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Lebrikizumab-Safety
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Lebrikizumab 125 mg SC administered as injection on Day 1, 29 and 57 during the 12-week treatment period. Participants were followed up further for 8 weeks during the safety follow-up period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Montelukast-Safety
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Montelukast 10 mg tablet administered orally once daily during the 12-week treatment period. Participants were followed up further for 8 weeks during the safety follow-up period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo-Safety
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Placebo matched to lebrikizumab 125 mg SC administered as injection on Day 1, 29 and 57 during the 12-week treatment period. Participants were followed up further for 8 weeks during the safety follow-up period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
10 Sep 2015 |
- Description of completed and ongoing clinical trials with lebrikizumab was updated.
- Biomarker subgroups for analysis to include blood eosinophil count was updated.
- Secondary efficacy endpoints, pharmacokinetic and pharmacodynamic endpoints, and exploratory efficacy endpoints were updated.
- Statistical analyses details were updated. |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |