A Study of Lebrikizumab in Adolescent Participants With U... | NCT01875003

NCT01875003

ID	Type	Description	Link
2012-000180-25	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Lebrikizumab High	Experimental	Participants with uncontrolled asthma on ICS therapy (total daily dose of 500-2000 micrograms [mcg] of fluticasone propionate dry powder inhaler [DPI] or equivalent) and a second controller medication, will receive SC injection of lebrikizumab (high dose) Q4W for 52 weeks during placebo-controlled period and up to 76 weeks or 104 weeks for participants who will be willing to take part in optional active-treatment extension period.	Drug: Lebrikizumab Drug: Standard of Care
Lebrikizumab Low	Experimental	Participants with uncontrolled asthma on ICS therapy (total daily dose of 500-2000 mcg of fluticasone propionate DPI or equivalent) and a second controller medication, will receive SC injection of lebrikizumab (low dose) Q4W for 52 weeks during placebo-controlled period and up to 76 weeks or 104 weeks for participants who will be willing to take part in optional active-treatment extension period.	Drug: Lebrikizumab Drug: Standard of Care
Placebo	Placebo Comparator	Participants with uncontrolled asthma on ICS therapy (total daily dose of 500-2000 mcg of fluticasone propionate DPI or equivalent) and a second controller medication, will receive SC injection of lebrikizumab matching placebo Q4W for 52 weeks during placebo-controlled period and then SC injection of lebrikizumab at high or low dose will be administered from Weeks 52 to 76 or 104 to participants who are willing to take part in optional active-treatment extension period.	Drug: Lebrikizumab Drug: Placebo Drug: Standard of Care

Name	Type	Description	Arm Group Labels	Other Names
Lebrikizumab	Drug	Lebrikizumab will be administered as SC injection at high or low dose Q4W.	Lebrikizumab High Lebrikizumab Low Placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Rate of Asthma Exacerbations During 52-Week Placebo Controlled Period	An asthma exacerbation is defined as new or increased asthma symptoms (including wheeze, cough, dyspnea, chest tightness, and/or night-time awakening due to these symptoms) that lead to treatment with systemic corticosteroids or to hospitalization. Treatment with systemic corticosteroids is defined as treatment with oral, intravenous (IV), or intramuscular (IM) corticosteroids for at least 3 days or an emergency department visit with at least 1 dose of IV or IM corticosteroids. Rate of asthma exacerbation = total number of exacerbation events divided by total follow-up time in patient years.	Baseline up to Week 52

Secondary Outcomes

Measure	Description	Time Frame
Percent Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Week 52	FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. The baseline FEV1 was obtained from the last spirometric analysis performed before the first study treatment administration. The percentage change in pre-bronchodilator FEV1 was defined as the change in FEV1 (in liters) from baseline divided by the FEV1 (in liters) at baseline multiplied by 100.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Asthma diagnosis for greater than or equal to (>/=) 12 months prior to Visit 1
Bronchodilator response during screening
Pre-bronchodilator FEV1 of 40 percent (%) - 90% predicted at both Visits 2 and 3
On high dose ICS therapy for >/= 6 months prior to Visit 1
On an eligible second controller medication for 6 months prior to Visit 1
Uncontrolled asthma as defined by the protocol both during screening and at the time of randomization
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 prior to 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 that meets the following criteria: Any infection requiring hospital admission or requiring treatment with IV or IM antibiotics within 4 weeks prior to Visit 1 or during screening; any active infection that required treatment with oral antibiotics within 2 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
History of active tuberculosis requiring treatment
Known immunodeficiency, including, but not limited to, human immunodeficiency virus (HIV) infection
Evidence of acute or chronic hepatitis or known liver cirrhosis
History of cystic fibrosis, bronchiectasis, and/or other clinically significant lung disease other than asthma
Diagnosis or history of 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 (whichever is longer) prior to Visit 1
Initiation of or change in allergen immunotherapy within 3 months prior to Visit 1 or during screening
History of bronchial thermoplasty

Contacts/Locations Module

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Southern California Research Center		Mission Viejo	California	92691	United States
Bensch Research Associates

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
35846226	Derived	Szefler SJ, Roberts G, Rubin AS, Zielen S, Kuna P, Alpan O, Anzures-Cabrera J, Chen Q, Holweg CTJ, Kaminski J, Putnam WS, Matthews JG, Kamath N. Efficacy, safety, and tolerability of lebrikizumab in adolescent patients with uncontrolled asthma (ACOUSTICS). Clin Transl Allergy. 2022 Jul 14;12(7):e12176. doi: 10.1002/clt2.12176. eCollection 2022 Jul.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Participants received subcutaneous (SC) injection of lebrikizumab matching placebo (1 placebo pre-filled syringe and 1 placebo vial) every 4 weeks (Q4W) for 52 weeks during placebo-controlled period. All participants were followed for safety for 24 weeks after last dose of study drug.
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

The intent-to-treat (ITT) population included all randomized participants who received at least one dose of study medication or have any post-baseline efficacy data.

Arm/Group Information

ID	Title	Description
BG000	Placebo	Participants received subcutaneous (SC) injection of lebrikizumab matching placebo (1 placebo pre-filled syringe and 1 placebo vial) every 4 weeks (Q4W) for 52 weeks during placebo-controlled period. All participants were followed for safety for 24 weeks after last dose of study drug.
BG001	Lebrikizumab 37.5 mg	Participants received SC injection of lebrikizumab at dose level of 37.5 mg (1 placebo pre-filled syringe and 1 active vial) Q4W for 52 weeks during placebo-controlled period. After Week 52, participants who were willing to take part in active-treatment extension, received same treatment up to Week 76 (if participants met protocol-defined criteria of asthma control from Week 52 to Week 76) or up to Week 104 (if participants did not meet protocol-defined criteria of asthma control from Week 52 to Week 76). All participants were followed for safety for 24 weeks after last dose of study drug.
BG002	Lebrikizumab 125 mg	Participants received SC injection of lebrikizumab at dose level of 125 mg (1 active pre-filled syringe and 1 placebo vial) Q4W for 52 weeks during placebo-controlled period. After Week 52, participants who were willing to take part in active-treatment extension, received same treatment up to Week 76 (if participants met protocol-defined criteria of asthma control from Week 52 to Week 76) or up to Week 104 (if participants did not meet protocol-defined criteria of asthma control from Week 52 to Week 76). All participants were followed for safety for 24 weeks after last dose of study drug.
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Intent-to-treat (ITT) population included all randomized participants who received at least one dose of study drug.

Mean

Standard Deviation

years

Title	Denominators	Categories
	ParticipantsBG000117 ParticipantsBG001113 ParticipantsBG002116 ParticipantsBG003

Sex: Female, Male

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000117 ParticipantsBG001113 ParticipantsBG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000117 ParticipantsBG001113 ParticipantsBG002

Race (NIH/OMB)

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000117 ParticipantsBG001113 ParticipantsBG002

Age group (years)

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000117 ParticipantsBG001113 ParticipantsBG002

Baseline Use of Inhaled Corticosteroid (ICS) and Long-Acting Beta-Agonist (LABA)

Reported is the baseline use of ICS (fluticasone proprionate dry powder inhaler [DPI] or equivalent) and LABA

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000117 ParticipantsBG001113 ParticipantsBG002

Number of Asthma Exacerbations in Last 12 Months

Number of Asthma Exacerbations within the last 12 months. Participants who reported ">10" events were assumed to have 11 events for the calculation of the mean value.

ITT population included all participants randomized in the study. The value of "n" signifies the number of participants evaluated at baseline. One participant was missing baseline assessment.

Mean

Standard Deviation

Asthma Exacerbations

Title	Denominators	Categories
	ParticipantsBG000117 ParticipantsBG001112

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Rate of Asthma Exacerbations During 52-Week Placebo Controlled Period

An asthma exacerbation is defined as new or increased asthma symptoms (including wheeze, cough, dyspnea, chest tightness, and/or night-time awakening due to these symptoms) that lead to treatment with systemic corticosteroids or to hospitalization. Treatment with systemic corticosteroids is defined as treatment with oral, intravenous (IV), or intramuscular (IM) corticosteroids for at least 3 days or an emergency department visit with at least 1 dose of IV or IM corticosteroids. Rate of asthma exacerbation = total number of exacerbation events divided by total follow-up time in patient years.

Adjusted exacerbation rate estimated from a Poisson regression model was reported. Analysis was performed on ITT population.

Posted

Number

events per patient year

Baseline up to Week 52

ID	Title	Description
OG000	Placebo	Participants received subcutaneous (SC) injection of lebrikizumab matching placebo (1 placebo pre-filled syringe and 1 placebo vial) every 4 weeks (Q4W) for 52 weeks during placebo-controlled period. All participants were followed for safety for 24 weeks after last dose of study drug.
OG001	Lebrikizumab 37.5 mg	Participants received SC injection of lebrikizumab at dose level of 37.5 mg (1 placebo pre-filled syringe and 1 active vial) Q4W for 52 weeks during placebo-controlled period. After Week 52, participants who were willing to take part in active-treatment extension, received same treatment up to Week 76 (if participants met protocol-defined criteria of asthma control from Week 52 to Week 76) or up to Week 104 (if participants did not meet protocol-defined criteria of asthma control from Week 52 to Week 76). All participants were followed for safety for 24 weeks after last dose of study drug.
OG002	Lebrikizumab 125 mg	Participants received SC injection of lebrikizumab at dose level of 125 mg (1 active pre-filled syringe and 1 placebo vial) Q4W for 52 weeks during placebo-controlled period. After Week 52, participants who were willing to take part in active-treatment extension, received same treatment up to Week 76 (if participants met protocol-defined criteria of asthma control from Week 52 to Week 76) or up to Week 104 (if participants did not meet protocol-defined criteria of asthma control from Week 52 to Week 76). All participants were followed for safety for 24 weeks after last dose of study drug.

Units	Counts
Participants	OG000117 OG001113 OG002116

Title

Denominators

Categories

Title	Measurements
	OG0000.43 OG0010.26 OG0020.21

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Adjusted exacerbation rates and rate ratios were estimated from a Poisson regression model with over-dispersion adjusted for the following covariates in addition to log(patient years) as an offset: number of asthma exacerbations within the last 12 months, baseline asthma medications and age group.					Adjusted Rate Ratio	0.60			2-Sided	95	0.35	1.03					Superiority

Secondary

Percent Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Week 52

FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. The baseline FEV1 was obtained from the last spirometric analysis performed before the first study treatment administration. The percentage change in pre-bronchodilator FEV1 was defined as the change in FEV1 (in liters) from baseline divided by the FEV1 (in liters) at baseline multiplied by 100.

ITT populaton; Here 'Number of Subjects Analysed' signifies number of participants evaluable for this outcome measure.

Posted

Mean

Standard Deviation

percent change

Week 52

ID	Title	Description
OG000	Placebo	Participants received subcutaneous (SC) injection of lebrikizumab matching placebo (1 placebo pre-filled syringe and 1 placebo vial) every 4 weeks (Q4W) for 52 weeks during placebo-controlled period. All participants were followed for safety for 24 weeks after last dose of study drug.
OG001	Lebrikizumab 37.5 mg	Participants received SC injection of lebrikizumab at dose level of 37.5 mg (1 placebo pre-filled syringe and 1 active vial) Q4W for 52 weeks during placebo-controlled period. After Week 52, participants who were willing to take part in active-treatment extension, received same treatment up to Week 76 (if participants met protocol-defined criteria of asthma control from Week 52 to Week 76) or up to Week 104 (if participants did not meet protocol-defined criteria of asthma control from Week 52 to Week 76). All participants were followed for safety for 24 weeks after last dose of study drug.

Secondary

Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Week 52

FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. The baseline FEV1 was obtained from the last spirometric analysis performed before the first study treatment administration. Reported is the absolute change from baseline in FEV1 to the end of the placebo-controlled period at Week 52.

ITT populaton; Here 'Number of Subjects Analysed' signifies number of participants evaluable for this outcome measure.

Posted

Mean

Standard Error

millilitre (mL)

Week 52

ID	Title	Description
OG000	Placebo	Participants received subcutaneous (SC) injection of lebrikizumab matching placebo (1 placebo pre-filled syringe and 1 placebo vial) every 4 weeks (Q4W) for 52 weeks during placebo-controlled period. All participants were followed for safety for 24 weeks after last dose of study drug.
OG001	Lebrikizumab 37.5 mg	Participants received SC injection of lebrikizumab at dose level of 37.5 mg (1 placebo pre-filled syringe and 1 active vial) Q4W for 52 weeks during placebo-controlled period. After Week 52, participants who were willing to take part in active-treatment extension, received same treatment up to Week 76 (if participants met protocol-defined criteria of asthma control from Week 52 to Week 76) or up to Week 104 (if participants did not meet protocol-defined criteria of asthma control from Week 52 to Week 76). All participants were followed for safety for 24 weeks after last dose of study drug.

Secondary

Time to First Asthma Exacerbation

An asthma exacerbation was defined as new or increased asthma symptoms (including wheeze, cough, dyspnea, chest tightness, and/or night-time awakening due to these symptoms) that lead to treatment with systemic corticosteroids or to hospitalization. Treatment with systemic corticosteroids was defined as treatment with oral, IV, or IM corticosteroids for at least 3 days or an emergency department visit with at least 1 dose of IV or IM corticosteroids. Median time to first protocol-defined asthma exacerbation was estimated using Kaplan-Meier analysis. 95% Confidence interval (CI) for median was computed using the method of Brookmeyer and Crowley.

ITT population. The data N/A in the results signifies that median and corresponding CI could not be calculated due to low number of participants who had an event.

Posted

Median

95% Confidence Interval

weeks

Baseline up to Week 52

ID	Title	Description
OG000	Placebo	Participants received subcutaneous (SC) injection of lebrikizumab matching placebo (1 placebo pre-filled syringe and 1 placebo vial) every 4 weeks (Q4W) for 52 weeks during placebo-controlled period. All participants were followed for safety for 24 weeks after last dose of study drug.
OG001	Lebrikizumab 37.5 mg	Participants received SC injection of lebrikizumab at dose level of 37.5 mg (1 placebo pre-filled syringe and 1 active vial) Q4W for 52 weeks during placebo-controlled period. After Week 52, participants who were willing to take part in active-treatment extension, received same treatment up to Week 76 (if participants met protocol-defined criteria of asthma control from Week 52 to Week 76) or up to Week 104 (if participants did not meet protocol-defined criteria of asthma control from Week 52 to Week 76). All participants were followed for safety for 24 weeks after last dose of study drug.

Secondary

Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Week 52

Measurement of FeNO (in parts per billion [ppb]) was performed using a hand-held portable NIOX MINO® device, in accordance with guidelines published by the American Thoracic Society (ATS) and described in the pulmonary function testing manual.

ITT population. Here 'Number of Subjects Analysed' signifies number of participants evaluable for this outcome measure, and 'n' signifies number of participants evaluable at specified time point, per arm, respectively.

Posted

Mean

Standard Deviation

ppb

Week 52

ID	Title	Description
OG000	Placebo	Participants received subcutaneous (SC) injection of lebrikizumab matching placebo (1 placebo pre-filled syringe and 1 placebo vial) every 4 weeks (Q4W) for 52 weeks during placebo-controlled period. All participants were followed for safety for 24 weeks after last dose of study drug.
OG001	Lebrikizumab 37.5 mg	Participants received SC injection of lebrikizumab at dose level of 37.5 mg (1 placebo pre-filled syringe and 1 active vial) Q4W for 52 weeks during placebo-controlled period. After Week 52, participants who were willing to take part in active-treatment extension, received same treatment up to Week 76 (if participants met protocol-defined criteria of asthma control from Week 52 to Week 76) or up to Week 104 (if participants did not meet protocol-defined criteria of asthma control from Week 52 to Week 76). All participants were followed for safety for 24 weeks after last dose of study drug.

Secondary

Change From Baseline in Standardized Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ+12) Overall Score at Week 52

The Standardized AQLQ+12 was used to assess the participants' asthma-specific health-related quality of life. The AQLQ+12 had a recall specification of 2 weeks. The AQLQ+12 was a 32-item questionnaire with 4 domains: activity limitations, symptoms, emotional function, and environmental stimuli. Each of the 32 questions were scored on a scale 1-7. The overall AQLQ+12 score is the mean of the responses to each of the 32 questions, and ranges from 1 to 7. A score 7 indicated no impairments due to asthma, and a score of 1 indicated severe impairment.

Posted

Mean

Standard Deviation

units on a scale

Week 52

ID	Title	Description
OG000	Placebo	Participants received subcutaneous (SC) injection of lebrikizumab matching placebo (1 placebo pre-filled syringe and 1 placebo vial) every 4 weeks (Q4W) for 52 weeks during placebo-controlled period. All participants were followed for safety for 24 weeks after last dose of study drug.
OG001	Lebrikizumab 37.5 mg	Participants received SC injection of lebrikizumab at dose level of 37.5 mg (1 placebo pre-filled syringe and 1 active vial) Q4W for 52 weeks during placebo-controlled period. After Week 52, participants who were willing to take part in active-treatment extension, received same treatment up to Week 76 (if participants met protocol-defined criteria of asthma control from Week 52 to Week 76) or up to Week 104 (if participants did not meet protocol-defined criteria of asthma control from Week 52 to Week 76). All participants were followed for safety for 24 weeks after last dose of study drug.

Secondary

Change From Baseline in Asthma Rescue Medication Use at Week 52

Participants were allowed to use short-acting bronchodilators as asthma rescue medication. Baseline asthma rescue medication use was defined as the average number of puffs per day over the 7 days prior to and on the day of randomization. Participants must have recorded their asthma rescue medication use for at least 4 days to have a baseline score calculated. The post-baseline asthma medication use for any timepoint was defined as the average number of puffs per day over the last 28 days on or prior to the timepoint. Participants must have recorded their asthma rescue medication use for at least 14 days during a 28-day interval to have a score calculated for the respective timepoint. For nebulizer use, one treatment (inhalation) was considered equivalent to 4 puffs.

Posted

Mean

Standard Deviation

puffs per day

Week 52

ID	Title	Description
OG000	Placebo	Participants received subcutaneous (SC) injection of lebrikizumab matching placebo (1 placebo pre-filled syringe and 1 placebo vial) every 4 weeks (Q4W) for 52 weeks during placebo-controlled period. All participants were followed for safety for 24 weeks after last dose of study drug.
OG001	Lebrikizumab 37.5 mg

Secondary

Rate of Urgent Asthma-Related Health Care Utilization (HCU) Events

Urgent asthma-related HCU events included hospitalizations, emergency department visits, and acute care visits. Rate of urgent asthma-related HCU events = total number of urgent asthma-related HCU events divided by total follow-up time in patient years.

ITT population.

Posted

Number

events per patient year

Baseline up to Week 52

ID	Title	Description
OG000	Placebo	Participants received subcutaneous (SC) injection of lebrikizumab matching placebo (1 placebo pre-filled syringe and 1 placebo vial) every 4 weeks (Q4W) for 52 weeks during placebo-controlled period. All participants were followed for safety for 24 weeks after last dose of study drug.
OG001	Lebrikizumab 37.5 mg	Participants received SC injection of lebrikizumab at dose level of 37.5 mg (1 placebo pre-filled syringe and 1 active vial) Q4W for 52 weeks during placebo-controlled period. After Week 52, participants who were willing to take part in active-treatment extension, received same treatment up to Week 76 (if participants met protocol-defined criteria of asthma control from Week 52 to Week 76) or up to Week 104 (if participants did not meet protocol-defined criteria of asthma control from Week 52 to Week 76). All participants were followed for safety for 24 weeks after last dose of study drug.
OG002

Secondary

Injection Acceptability Questionnaire (IAQ) Score

The acceptability of the injections of study drug was addressed by measuring the level of pain that participants experienced. Participants assessed pain associated with study drug administration using the IAQ within 10 minutes of study drug administration. The IAQ score ranged from 0 to 10; where 0 = no pain and 10 = worst pain imaginable.

Posted

Mean

Standard Deviation

units on a scale

Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48

ID	Title	Description
OG000	Placebo	Participants received subcutaneous (SC) injection of lebrikizumab matching placebo (1 placebo pre-filled syringe and 1 placebo vial) every 4 weeks (Q4W) for 52 weeks during placebo-controlled period. All participants were followed for safety for 24 weeks after last dose of study drug.
OG001	Lebrikizumab 37.5 mg	Participants received SC injection of lebrikizumab at dose level of 37.5 mg (1 placebo pre-filled syringe and 1 active vial) Q4W for 52 weeks during placebo-controlled period. After Week 52, participants who were willing to take part in active-treatment extension, received same treatment up to Week 76 (if participants met protocol-defined criteria of asthma control from Week 52 to Week 76) or up to Week 104 (if participants did not meet protocol-defined criteria of asthma control from Week 52 to Week 76). All participants were followed for safety for 24 weeks after last dose of study drug.

Secondary

Minimum Observed Serum Concentration (Ctrough) for Lebrikizumab

Participants who received at least one dose of lebrikizumab and had at least one post-baseline evaluable sample were included in the analysis. Results of post-dose samples which were less than reportable were set to 0.045 micrograms per milliliter (mcg/mL) that is half of minimum quantifiable concentration value (0.09 mcg/mL).

Here 'Number of Subjects Analysed' signifies number of participants evaluable for this outcome measure, and 'n' signifies number of participants evaluable at specified time point, per arm, respectively.

Posted

Mean

Standard Deviation

mcg/mL

Predose (Hour 0) at Weeks 4, 12, 24, 36, and 52

ID	Title	Description
OG000	Lebrikizumab 37.5 mg	Participants received SC injection of lebrikizumab at dose level of 37.5 mg (1 placebo pre-filled syringe and 1 active vial) Q4W for 52 weeks during placebo-controlled period. After Week 52, participants who were willing to take part in active-treatment extension, received same treatment up to Week 76 (if participants met protocol-defined criteria of asthma control from Week 52 to Week 76) or up to Week 104 (if participants did not meet protocol-defined criteria of asthma control from Week 52 to Week 76). All participants were followed for safety for 24 weeks after last dose of study drug.
OG001	Lebrikizumab 125 mg	Participants received SC injection of lebrikizumab at dose level of 125 mg (1 active pre-filled syringe and 1 placebo vial) Q4W for 52 weeks during placebo-controlled period. After Week 52, participants who were willing to take part in active-treatment extension, received same treatment up to Week 76 (if participants met protocol-defined criteria of asthma control from Week 52 to Week 76) or up to Week 104 (if participants did not meet protocol-defined criteria of asthma control from Week 52 to Week 76). All participants were followed for safety for 24 weeks after last dose of study drug.

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Participants received SC injection of lebrikizumab matching placebo (1 placebo pre-filled syringe and 1 placebo vial) Q4W for 52 weeks during placebo-controlled period. All participants were followed for safety for 24 weeks after last dose of study drug.	56	3	56	23	56
EG001	Lebrikizumab 37.5 mg	Participants received SC injection of lebrikizumab at dose level of 37.5 mg (1 placebo pre-filled syringe and 1 active vial) Q4W for 52 weeks during placebo-controlled period. After Week 52, participants who were willing to take part in active-treatment extension, received same treatment up to Week 76 (if participants met protocol-defined criteria of asthma control from Week 52 to Week 76) or up to Week 104 (if participants did not meet protocol-defined criteria of asthma control from Week 52 to Week 76). All participants were followed for safety for 24 weeks after last dose of study drug.	113	6	113	67	113
EG002	Lebrikizumab 125 mg	Participants received SC injection of lebrikizumab at dose level of 125 mg (1 active pre-filled syringe and 1 placebo vial) Q4W for 52 weeks during placebo-controlled period. After Week 52, participants who were willing to take part in active-treatment extension, received same treatment up to Week 76 (if participants met protocol-defined criteria of asthma control from Week 52 to Week 76) or up to Week 104 (if participants did not meet protocol-defined criteria of asthma control from Week 52 to Week 76). All participants were followed for safety for 24 weeks after last dose of study drug.	116	8	116	72	116
EG003	Placebo/ Lebrikizumab 37.5 mg	Participants in 'Placebo' group who were willing to take part in optional active-treatment extension period and who were randomized to this group received SC injection of lebrikizumab at dose level of 37.5 mg (1 placebo pre-filled syringe and 1 active vial) Q4W from Weeks 52 to Week 76 (if participants met protocol-defined criteria of asthma control from Week 52 to Week 76) or up to Week 104 (if participants did not meet protocol-defined criteria of asthma control from Week 52 to Week 76). All participants were followed for safety for 24 weeks after last dose of study drug.	30	3	30	23	30
EG004	Placebo/ Lebrikizumab 125 mg	Participants in 'Placebo' group who were willing to take part in optional active-treatment extension period and who were randomized to this group received SC injection of lebrikizumab at dose level of 125 mg (1 active pre-filled syringe and 1 placebo vial) Q4W from Weeks 52 to Week 76 (if participants met protocol-defined criteria of asthma control from Week 52 to Week 76) or up to Week 104 (if participants did not meet protocol-defined criteria of asthma control from Week 52 to Week 76). All participants were followed for safety for 24 weeks after last dose of study drug.	31	4	31	24	31

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Eosinophilia	Blood and lymphatic system disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 events0 affected56 at risk EG0011 events1 affected113 at risk EG0020 events0 affected116 at risk EG0030 events0 affected30 at risk EG0040 events0 affected31 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 events0 affected56 at risk EG0010 events0 affected113 at risk EG0020 events0 affected116 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 events1 affected56 at risk EG0010 events0 affected113 at risk EG0020 events0 affected116 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 events1 affected56 at risk EG0010 events0 affected113 at risk EG0020 events0 affected116 at risk EG003
Anaphylactic reaction	Immune system disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 events0 affected56 at risk EG0010 events0 affected113 at risk EG0021 events1 affected116 at risk EG003
Anaphylactic shock	Immune system disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 events0 affected56 at risk EG0010 events0 affected113 at risk EG0021 events1 affected116 at risk EG003
Appendicitis	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0000 events0 affected56 at risk EG0011 events1 affected113 at risk EG0020 events0 affected116 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0000 events0 affected56 at risk EG0010 events0 affected113 at risk EG0021 events1 affected116 at risk EG003
Infection	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0000 events0 affected56 at risk EG0011 events1 affected113 at risk EG0020 events0 affected116 at risk EG003
Lower respiratory tract infection	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0000 events0 affected56 at risk EG0011 events1 affected113 at risk EG0020 events0 affected116 at risk EG003
Pulmonary tuberculosis	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0000 events0 affected56 at risk EG0010 events0 affected113 at risk EG0021 events1 affected116 at risk EG003
Sinusitis	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0000 events0 affected56 at risk EG0010 events0 affected113 at risk EG0020 events0 affected116 at risk EG003
Viral infection	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0000 events0 affected56 at risk EG0011 events1 affected113 at risk EG0020 events0 affected116 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 events1 affected56 at risk EG0010 events0 affected113 at risk EG0021 events1 affected116 at risk EG003
Metabolic syndrome	Metabolism and nutrition disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 events0 affected56 at risk EG0010 events0 affected113 at risk EG0021 events1 affected116 at risk EG003
Type 1 diabetes mellitus	Metabolism and nutrition disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 events0 affected56 at risk EG0010 events0 affected113 at risk EG0020 events0 affected116 at risk EG003
Dizziness	Nervous system disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 events0 affected56 at risk EG0010 events0 affected113 at risk EG0021 events1 affected116 at risk EG003
Headache	Nervous system disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 events0 affected56 at risk EG0010 events0 affected113 at risk EG0020 events0 affected116 at risk EG003
Abortion spontaneous	Pregnancy, puerperium and perinatal conditions	MedDRA 19.1	Non-systematic Assessment	EG0000 events0 affected56 at risk EG0010 events0 affected113 at risk EG0020 events0 affected116 at risk EG003
Depression	Psychiatric disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 events0 affected56 at risk EG0010 events0 affected113 at risk EG0021 events1 affected116 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 events1 affected56 at risk EG0012 events2 affected113 at risk EG0022 events2 affected116 at risk EG003
Asthmatic crisis	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 events0 affected56 at risk EG0011 events1 affected113 at risk EG0020 events0 affected116 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 events1 affected56 at risk EG0010 events0 affected113 at risk EG0020 events0 affected116 at risk EG003
Angioedema	Skin and subcutaneous tissue disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 events0 affected56 at risk EG0011 events1 affected113 at risk EG0020 events0 affected116 at risk EG003
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 events0 affected56 at risk EG0011 events1 affected113 at risk EG0020 events0 affected116 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Conjunctivitis allergic	Eye disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 events0 affected56 at risk EG0013 events1 affected113 at risk EG0020 events0 affected116 at risk EG0032 events2 affected30 at risk EG0040 events0 affected31 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 events0 affected56 at risk EG0013 events1 affected113 at risk EG0026 events6 affected116 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 events1 affected56 at risk EG0012 events2 affected113 at risk EG0022 events2 affected116 at risk EG003
Injection site extravasation	General disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 events0 affected56 at risk EG0018 events2 affected113 at risk EG00212 events2 affected116 at risk EG003
Injection site induration	General disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 events0 affected56 at risk EG0011 events1 affected113 at risk EG0023 events3 affected116 at risk EG003
Injection site pain	General disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 events0 affected56 at risk EG0014 events2 affected113 at risk EG0022 events2 affected116 at risk EG003
Acute sinusitis	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0000 events0 affected56 at risk EG0012 events2 affected113 at risk EG0024 events3 affected116 at risk EG003
Bronchitis	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0002 events2 affected56 at risk EG00112 events10 affected113 at risk EG0027 events6 affected116 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0001 events1 affected56 at risk EG0013 events3 affected113 at risk EG0023 events3 affected116 at risk EG003
Influenza	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0000 events0 affected56 at risk EG0015 events5 affected113 at risk EG0029 events6 affected116 at risk EG003
Laryngitis	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0000 events0 affected56 at risk EG0011 events1 affected113 at risk EG0021 events1 affected116 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0005 events4 affected56 at risk EG00131 events14 affected113 at risk EG00218 events13 affected116 at risk EG003
Pharyngitis	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0005 events5 affected56 at risk EG00114 events10 affected113 at risk EG00228 events18 affected116 at risk EG003
Respiratory tract infection	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0000 events0 affected56 at risk EG0011 events1 affected113 at risk EG0025 events5 affected116 at risk EG003
Rhinitis	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0001 events1 affected56 at risk EG0015 events5 affected113 at risk EG0026 events6 affected116 at risk EG003
Sinusitis	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0004 events4 affected56 at risk EG0013 events2 affected113 at risk EG0024 events3 affected116 at risk EG003
Tonsillitis	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0002 events2 affected56 at risk EG0019 events9 affected113 at risk EG00211 events8 affected116 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0003 events3 affected56 at risk EG00122 events16 affected113 at risk EG00214 events11 affected116 at risk EG003
Viral infection	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0000 events0 affected56 at risk EG0011 events1 affected113 at risk EG0023 events3 affected116 at risk EG003
Viral pharyngitis	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0000 events0 affected56 at risk EG0011 events1 affected113 at risk EG0021 events1 affected116 at risk EG003
Viral upper respiratory tract infection	Infections and infestations	MedDRA 19.1	Non-systematic Assessment	EG0000 events0 affected56 at risk EG0012 events2 affected113 at risk EG0024 events2 affected116 at risk EG003
Blood creatine phosphokinase increased	Investigations	MedDRA 19.1	Non-systematic Assessment	EG0002 events1 affected56 at risk EG0012 events2 affected113 at risk EG0023 events3 affected116 at risk EG003
Dizziness	Nervous system disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 events1 affected56 at risk EG0013 events3 affected113 at risk EG0020 events0 affected116 at risk EG003
Headache	Nervous system disorders	MedDRA 19.1	Non-systematic Assessment	EG0002 events2 affected56 at risk EG00120 events8 affected113 at risk EG00222 events11 affected116 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Non-systematic Assessment	EG00021 events12 affected56 at risk EG00153 events25 affected113 at risk EG00258 events31 affected116 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0001 events1 affected56 at risk EG0018 events6 affected113 at risk EG0023 events3 affected116 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 events0 affected56 at risk EG00110 events7 affected113 at risk EG0020 events0 affected116 at risk EG003
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0002 events1 affected56 at risk EG0014 events3 affected113 at risk EG0028 events6 affected116 at risk EG003
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 events0 affected56 at risk EG0011 events1 affected113 at risk EG0020 events0 affected116 at risk EG003
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 19.1	Non-systematic Assessment	EG0000 events0 affected56 at risk EG0011 events1 affected113 at risk EG0021 events1 affected116 at risk EG003

The enrollment was closed, and dosing was terminated in this study following the sponsor's decision to discontinue development of lebrikizumab. Thus, this study was treated as exploratory (rather than confirmatory).

Certain Agreements

ID	Term
D001249	Asthma

Ancestor Terms

ID	Term
D001982	Bronchial Diseases
D012140	Respiratory Tract Diseases
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases
D012130	Respiratory Hypersensitivity
D006969	Hypersensitivity, Immediate
D006967	Hypersensitivity
D007154	Immune System Diseases

ID	Term
C561806	lebrikizumab
D059039	Standard of Care

ParticipantsBG003346

ParticipantsBG002116

ParticipantsBG003345

Participants received SC injection of lebrikizumab at dose level of 37.5 mg (1 placebo pre-filled syringe and 1 active vial) Q4W for 52 weeks during placebo-controlled period. After Week 52, participants who were willing to take part in active-treatment extension, received same treatment up to Week 76 (if participants met protocol-defined criteria of asthma control from Week 52 to Week 76) or up to Week 104 (if participants did not meet protocol-defined criteria of asthma control from Week 52 to Week 76). All participants were followed for safety for 24 weeks after last dose of study drug.

EG0041 events1 affected31 at risk

EG0040 events0 affected31 at risk

EG0041 events1 affected31 at risk

EG0040 events0 affected31 at risk

EG0043 events2 affected31 at risk

EG0040 events0 affected31 at risk

EG0041 events1 affected31 at risk

EG0042 events2 affected31 at risk

EG0043 events2 affected31 at risk

EG0041 events1 affected31 at risk

EG0046 events3 affected31 at risk

EG0047 events4 affected31 at risk

EG0041 events1 affected31 at risk

EG0042 events2 affected31 at risk

EG00410 events7 affected31 at risk

EG0047 events4 affected31 at risk

EG0044 events2 affected31 at risk

EG0043 events3 affected31 at risk

EG0042 events1 affected31 at risk

EG0043 events3 affected31 at risk

EG0046 events2 affected31 at risk

EG0044 events2 affected31 at risk

EG0042 events2 affected31 at risk

EG0044 events3 affected31 at risk

EG0040 events0 affected31 at risk

EG0042 events2 affected31 at risk

EG0047 events6 affected31 at risk

EG00443 events15 affected31 at risk

EG0041 events1 affected31 at risk

EG0042 events2 affected31 at risk

EG0045 events2 affected31 at risk

EG0042 events2 affected31 at risk

EG0041 events1 affected31 at risk

ID	Term
D019984	Quality Indicators, Health Care
D011787	Quality of Health Care
D006298	Health Services Administration
D017530	Health Care Quality, Access, and Evaluation