C38072-AS-30025

Teva Branded Pharmaceutical Products, R&D Inc

41 Moores Road, Frazer, United States, 19355

Director, Clinical Research, Teva Branded Pharmaceutical Products, R&D Inc, 001 2155913000, ustevatrials@tevapharm.com

Director, Clinical Research, Teva Branded Pharmaceutical Products, R&D Inc, 001 2155913000, ustevatrials@tevapharm.com

Yes

No

Yes

Final

31 Jan 2018

No

Yes

31 Jan 2018

Yes

The purpose of this study was to establish the safety and efficacy of the subcutaneous formulation of reslizumab in participants with uncontrolled asthma and elevated blood eosinophils.

This study was conducted in full accordance with the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Consolidated Guideline (E6) and any applicable national and local laws and regulations (eg, Code of Federal Regulations Title 21, Parts 11, 50, 54, 56, 312, and 314; European Union Directive 2001/20/EC on the approximation of the laws, regulations, and administrative provisions of the Member States relating to the implementation of GCP in the conduct of clinical studies on medicinal products for human use). Written and/or oral information about the study was provided to all participants in a language understandable by the participants. The information included an adequate explanation of the aims, methods, anticipated benefits, potential hazards, and insurance arrangements in force. Written informed consent was obtained from each participant before any study procedures or assessments were done. It was explained to the participants that they were free to refuse entry into the study and free to withdraw from the study at any time without prejudice to future treatment.

12 Aug 2015

No

No

Argentina: 27

Australia: 1

Belgium: 20

Canada: 18

Germany: 28

Spain: 6

France: 1

Hungary: 35

Israel: 34

Japan: 6

Mexico: 8

New Zealand: 2

Poland: 22

Romania: 18

Russian Federation: 45

Turkey: 4

Ukraine: 76

United States: 105

South Africa: 12

468

130

0

0

0

0

0

53

348

67

0

Overall Study (overall period)

Randomised - controlled

Yes

Placebo

Solution for injection in pre-filled syringe

Subcutaneous use

Matching placebo administered once every 4 weeks (+/-7 days)

Resizumab

CEP-38072

Solution for injection in pre-filled syringe

Subcutaneous use

Reslizumab 110 mg once every 4 weeks (+/-7 days)

Placebo

Reslizumab 110 mg

Placebo

Reslizumab 110 mg

CAE is deterioration in asthma control, determined by investigator and evidenced by new/worsening symptoms based on history, asthma control diary, physical examination, and/or ambulatory or clinic visit assessment of lung function and that resulted in a medical intervention, including at least 1 of the following: use of systemic corticosteroids or at least a doubling from a stable maintenance oral corticosteroid dose for at least 3 days; asthma-specific hospital admission; asthma-specific ER department visit. Adjusted CAE rate and CIs were based on Negative Binomial regression model adjusted for stratification factors. Offset variable calculated as the logarithm of treatment duration minus the summed duration of exacerbations during treatment period. ITT population included all randomized participants, excluding participants from the site terminated due to GCP issues. Treatment based on to which participants were randomized, regardless of which treatment they received

Primary

Day 1 to Week 52

The frequency of CAEs was analyzed using the generalized linear model (GLM) for data from the negative binomial distributions that is commonly referred to as the negative binomial (NB) regression model. The primary NB model included the treatment group, randomization stratification factors, and number of prior exacerbations as model factors and the logarithm of treatment duration excluding the summed duration of exacerbations in the treatment period as an offset variable.

Placebo v Reslizumab 110 mg

464

Pre-specified

0.79

2-sided

Change in pre-bronchodilator FEV1 from baseline to week 52 is presented. FEV1 is a standard measurement of air movement in the lungs of participants with asthma obtained from pulmonary function tests. It is the volume of air expired in the first second of a forced expiration using a spirometer. Analysis of the change from baseline to each visit was performed using a mixed effect model for repeated measures (MMRM) including fixed effects for treatment, visit, treatment by visit interaction, age group, blood eosinophil counts at enrollment, and sex, height and baseline value as covariates, and participant as a random effect. ITT includes all randomized participants, excluding participants from the site terminated due to GCP issues. Treatment was based on the treatment to which participants were randomized, regardless of which treatment they received. Overall number of participants analyzed=participants with both baseline and Week 52 FEV1 values available.

Secondary

Baseline, Week 52

AQLQ is a 32-item instrument administered as a self-assessment. AQLQ+12 is a modified version of AQLQ developed to measure functional impairments of participants aged 12-70 years. It is divided into 4 domains: activity limitation, symptoms, emotional function, and environmental stimuli. Participants were asked to recall their experiences during the last 2 weeks and respond to each question on a 7-point scale (1=severe impairment, 7=no impairment), where higher scores indicated "better quality of life." Overall AQLQ+12 score is the mean of all 32 responses. Analysis of the change from baseline to each visit was performed using a MMRM including fixed effects for treatment, visit, treatment by visit interaction, age group, blood eosinophil counts at enrollment, and sex, height and baseline value as covariates, and participant as a random effect. ITT population aged 12-70 years. Overall number of participants analyzed=participants with both baseline and Week 52 AQLQ+12 score available.

Secondary

Baseline, Week 52

ACQ-6 is a 6-item asthma assessment tool. 6 questions are self-assessments, 5 assessing asthma symptoms: night waking, symptoms on waking, activity limits, shortness of breath, wheezing, and 1 question for short-acting bronchodilator use. Each item has possible score ranges from 0-6, and total score is mean of all responses. Total score range from 0-6 (0=totally controlled, 6=severely uncontrolled). Higher score=poorer asthma control. Analysis of change from baseline to each visit performed using a MMRM including fixed effects for treatment, visit, treatment by visit interaction, age group, eosinophil count at enrollment, and sex, height and baseline value as covariates, and participant as a random effect. ITT includes all randomized participants, excluding the site terminated due to GCP issues. Treatment based on what participants were randomized to, regardless of which they received. Number of participants analyzed=participants with both baseline and Week 52 ACQ-6 score available.

Secondary

Baseline, Week 52

Asthma symptoms recorded by participant each day and night in an asthma diary. Night score assessed on 5-point scale: 0=no symptoms to 4=bad night. Day score assessed on 6-point scale where 0=very well to 5=asthma very severe. Total symptom score calculated by taking the sum of the night and day symptom scores recorded ranging from 0 (no symptom) to 9 (severe symptom). Lower symptom score indicated better outcome. Analysis of the change from baseline to each visit was performed using a MMRM including fixed effects for treatment, visit, treatment by visit interaction, age group, eosinophil count at enrollment, and sex, height and baseline value as covariate, and participant as a random effect. ITT=all randomized participants, excluding from site terminated due to GCP issues. Treatment based on treatment to which participants were randomized, regardless of treatment received. Overall number of participants analyzed=participants with both baseline and Week 52 total asthma symptom score.

Secondary

Baseline, Week 52

The percentage of asthma control days over 52 weeks of treatment is presented. An asthma control day was defined as a day on which the participant used less than or equal to 2 puffs of inhaled short-acting beta-agonist, had no nighttime awakenings, and experienced no asthma exacerbations. Analysis of the change from baseline to each visit was performed using a mixed effect MMRM including fixed effects for treatment, visit, treatment by visit interaction, age group, blood eosinophil counts at enrollment, and sex, height and baseline value as covariates, and participant as a random effect. ITT population includes all randomized participants, excluding participants from the site terminated due to GCP issues. Treatment was based on the treatment to which participants were randomized, regardless of which treatment they actually received.

Secondary

Day 1 to Week 52

SGRQ is 17-item questionnaire with 50 weighted responses that provides total score and 3 component scores: Symptoms (distress caused by respiratory symptoms), Activity (physical activities cause/limited by breathlessness), and Impacts (social/psychological effects). Total score and each of the SGRQ subscores are from 0-100 where 0=best, 100=worst health. Increase in score indicates worsening health. Analysis of the change from baseline to each visit was performed using a MMRM including fixed effects for treatment, visit, treatment by visit interaction, age group, eosinophil counts at enrollment, and sex, height and baseline value as covariates, and participant as a random effect. ITT=all randomized participants, excluding site terminated due to GCP issues. Treatment was based on treatment to which participants were randomized, regardless of which treatment they received. Overall number of participants analyzed=participants with both baseline and Week 32 SGRQ total scores available.

Secondary

Baseline, Week 32

CAE defined as deterioration in asthma control, as determined by investigator and new or worsening asthma symptoms based on history, asthma control diary, physical examination, and/or ambulatory/clinic visit assessment of lung function and that resulted in a medical intervention, including 1 of the following: use of systemic corticosteroids or at least a doubling from a stable maintenance oral corticosteroid dose for at least 3 days; asthma-specific hospital admission; asthma-specific ER visit. KM method used to estimate/compare the distributions of time to first CAE between groups. Participants without event during treatment period were censored at either the date of the end of treatment visit for participants who completed treatment or at date of last dose for participants who discontinued. ITT=all randomized participants, excluding site terminated due to GCP issues. Treatment based on treatment to which participants were randomized regardless of which treatment they received.

Secondary

Day 1 to Week 52

CAE defined as deterioration in asthma control, as determined by investigator and new or worsening asthma symptoms based on history, asthma control diary, physical examination, and/or ambulatory/clinic visit assessment of lung function and that resulted in a medical intervention, including 1 of the following: use of systemic corticosteroids or at least a doubling from a stable maintenance oral corticosteroid dose for at least 3 days; asthma-specific hospital admission; asthma-specific ER visit. Frequency of CAEs over treatment period expressed as adjusted CAEs rate in 52 weeks. Adjusted CAE rate and CIs based on Negative Binomial regression model adjusted for stratification factors (age group, blood eosinophil group) and number of prior exacerbations, and an offset variable. ITT=all randomized participants, excluding site terminated due to GCP issues. Treatment based on treatment to which participants were randomized regardless of which treatment they received.

Secondary

Day 1 to Week 52

Moderate exacerbation defined as deterioration in asthma control determined by investigator and new/worsening symptoms based on history, asthma diary, physical exam, and/or ambulatory or clinic visit assessment of lung function and that resulted in a medical intervention requiring additional asthma controller medication that was not a systemic corticosteroid and did not result in an asthma-specific hospitalization or ER visit (that is, a medical intervention that did not meet criteria for primary endpoint). Frequency of moderate exacerbations over treatment period expressed as adjusted exacerbation rate in 52 weeks. Adjusted exacerbation rate and CIs based on Negative Binomial regression model adjusted for stratification factors (age group, eosinophil group) and number of prior exacerbations, and offset variable. ITT=all randomized participants, excluding site terminated due to GCP issues. Treatment based on treatment participants were randomized to, regardless of what was received.

Secondary

Day 1 to Week 52

From the first dose of study drug to the end of treatment visit (Week 52) for completed participants and between the first dose of study drug and 4 weeks after the last dose of study drug for participants who discontinued treatment early.

1 participant randomized to the placebo group was treated with reslizumab 110 mg at 1 study visit and counted in the reslizumab 110 mg arm for safety.There were no deaths during the treatment period. 1 death in the reslizumab group occurred 48 days after the participant's last dose.

20.0

Reslizumab 110 mg

Placebo