Asthma, Elevated Blood Eosinophils, Oral Corticosteroid Dependence
Conditions
Keywords
Asthma, Elevated Blood Eosinophils, Oral corticosteroid dependence, Reslizumab
Brief summary
The primary objective of the study is to determine the ability of reslizumab administered by subcutaneous injection to produce a corticosteroid-sparing effect in patients with oral corticosteroid (OCS)-dependent asthma and elevated blood eosinophils, without loss of asthma control.
Interventions
DRUGReslizumab
Reslizumab 110 mg was administered by qualified study personnel as subcutaneous injections in the upper arm(s) once every 4 weeks for a total of 6 doses. Drug was supplied in pre-filled syringes.
DRUGPlacebo
Placebo was administered by qualified study personnel as subcutaneous injections in the upper arm(s) once every 4 weeks for a total of 6 doses. Drug was supplied in pre-filled syringes.
DRUGNon-Oral Corticosteroid (non-OCS) Asthma Medication
Participants continue using their non-OCS background asthma medications without change during the study's treatment period.
After screening and prior to study start, the participant's OCS dose was adjusted to determine the minimal effective OCS requirement.
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. The patient is male or female, 12 years of age and older, with a previous diagnosis of asthma. 2. Written informed consent is obtained. 3. The patient requires daily maintenance dose of prednisone or equivalent for asthma of between 5 and 40 mg during the 3 months prior to screening. 4. The patient has a documented elevated blood eosinophils at screening or during the previous 12 months. 5. The patient has required high dose ICS plus another asthma controller for at least 6 months prior to screening. 6. The patient has FEV1 reversibility to inhaled SABA or historical reversibility within the previous 24 months. * Other criteria may apply, please contact the investigator for more information.
Exclusion criteria
1. The patient has any clinically significant, uncontrolled medical condition that would interfere with the study schedule or procedures and interpretation of efficacy results or would compromise the patient's safety. 2. The patient has another confounding underlying lung disorder. 3. The patient has a known hypereosinophilic syndrome. 4. The patient has a history of any malignancy within 5 years of the screening visit, except for treated and cured non-melanoma skin cancers. 5. The patient is pregnant or intends to become pregnant during the study or is lactating. 6. The patient required treatment for an asthma exacerbation within 4 weeks of screening. 7. The patient is a current smoker or has a smoking history ≥10 pack-years. 8. The patient is currently using any systemic immunosuppressive or immunomodulatory biologic except maintenance OCS for the treatment of asthma. 9. The patient participated in a clinical study within 30 days or 5 half-lives of the investigational drug before screening, whichever is longer. 10. The patient was previously exposed to benralizumab within 12 months of screening. 11. The patient was previously exposed to reslizumab. 12. The patient has a history of immunodeficiency disorder including human immunodeficiency virus. 13. The patient has current suspected drug and/or alcohol abuse. 14. The patient has had an active helminthic parasitic infection or was treated for one within 6 months of screening. 15. The patient has a history of allergic reactions or hypersensitivity to any component of the study drug. * Other criteria may apply, please contact the investigator for more information.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Reduction In Daily Oral Corticosteroid (OCS) Dose During Weeks 20-24 As Compared to the Optimized Dose At Baseline | Baseline (Day 1), Weeks 20-24 | The primary endpoint was the 5-level categorized percent reduction in OCS dose during weeks 20 to 24 compared with the optimized dose at baseline. The primary analysis incorporated data from all randomized patients. Analysis of the primary and secondary variables related to categorical OCS dose reduction incorporated missing data as non-responders. No decrease indicates there was no decrease in OCS, loss of baseline asthma control during weeks 20 to 24, or discontinuation from study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving an OCS Dose of <=5 mg at Weeks 20-24 While Maintaining Asthma Control | Weeks 20-24 | Percentage of participants whose OCS dose at weeks 20-24 was \<=5 mg and they maintained asthma control. Patients listed as no had a week 20-24 OCS dose \> 5 mg, or whose OCS dose was \<=5 mg at weeks 20-24 but did not maintain asthma control, or they discontinued from study drug. |
| Percent Change From Baseline in Daily Oral Corticosteroid (OCS) Dose During Weeks 20-24 Using a Mixed Model for Repeated Measures | Baseline (Day 1), Weeks 20-24 | The baseline OCS dose is the prescribed optimized OCS dose following the OCS optimization period. Endpoint data are presented using an on-treatment approach. In this context, 'endpoint' was defined as the last observation obtained at a scheduled or qualified early termination visit during the treatment period. Weeks 20-24 data is included between the Week 20 dose and Week 24 for completed patients; last dose of study drug to 4 weeks after the last dose of study drug for patients who discontinued treatment early. Measurements collected outside of these defined timeframes are excluded from the analyses. The mixed model repeated measures (MMRM) included fixed effects for treatment, visit, treatment by visit interaction, age group, and OCS dose group, duration of OCS use and baseline value as covariates, and patient as a random effect. Unstructured covariance was assumed for the repeated measures. |
| Percentage of Participants Achieving a >=5 mg Reduction in OCS Dose at Weeks 20-24 Compared to Baseline While Maintaining Asthma Control | Baseline (Day 1), Weeks 20-24 | Percentage of participants whose OCS dose at weeks 20-24 was reduced by at least 5mg from baseline and maintained asthma control. Patients listed as no had a week 20-24 OCS dose that did not meet the threshold of a 5mg reduction, or whose OCS dose met the threshold but did not maintain asthma control, or discontinued from study drug. |
| Percentage of Participants Achieving a >=50% Reduction in OCS Dose at Weeks 20-24 Compared to Baseline While Maintaining Asthma Control | Baseline (Day 1), Weeks 20-24 | Percentage of patients whose OCS dose at weeks 20-24 was reduced \>=50% compared to baseline while maintaining asthma control. Patients listed as no did not achieve the 50% reduction in baseline OCS dose goal, or did achieve that goal but lost asthma control during weeks 20 to 24, or discontinued from study drug. |
| Percentage of Participants Achieving an OCS Dose of 0 mg at Weeks 20-24 While Maintaining Asthma Control | Weeks 20-24 | Percentage of participants who discontinue use of OCS during weeks 20-24 while maintaining asthma control. Patients listed as no continued to use OCS during weeks 20-24, or who discontinued use of OCS during weeks 20-24 but lost control of their asthma, or discontinued from study drug. |
| Participants With Treatment-Emergent Anti-Drug Antibody (ADA) Responses | Weeks 4, 8, 12, 24 or early withdrawal. | Treatment-emergent responses were defined as a positive sample post-baseline (negative baseline) OR a titer increase of \>=4-fold relative to a positive baseline sample. Two types of antibody assay were performed, an immunogenicity status assay (ADA) and neutralizing assay (NAb). The ADA assay produces a positive or negative result. For samples with a positive result, a neutralizing assay was performed, which also produces a positive or negative result. |
| Participants With Adverse Events | Day 1 up to Week 24 (end of treatment visit); Data were included between Day 1 and Week 24 for completed patients, and Day 1 and 4 weeks after the last dose of study drug for patients who discontinued treatment early. | An adverse event is any untoward medical occurrence in a patient administered a pharmaceutical product, regardless of whether it has a causal relationship with this treatment. In this study, asthma exacerbations (which are efficacy parameters) should not be recorded as adverse events unless assessed by the investigator as more severe than the patient's usual disease course. Relation of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes. Treatment-related adverse events or adverse events related to OCS use included events with missing relationship to study drug or OCS use, respectively. |
| Annualized Rate of Clinical Asthma Exacerbations (CAEs) | Day 1 through Week 24 | The annual exacerbation rate is based on clinical asthma exacerbations reported by the investigator in the eCRF. |
Countries
Argentina, Australia, Belgium, Czechia, France, Germany, Hungary, Israel, Italy, Mexico, Netherlands, Poland, Russia, South Korea, Spain, Ukraine, United States
Participant flow
Pre-assignment details
A total of 273 patients with OCS-dependent severe eosinophilic asthma were screened, and 180 of these patients (at 78 centers) were considered eligible for enrollment. Three of the eligible patients were not randomized due to failure to meet randomization criteria.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching placebo was administered by subcutaneous injection (sc) 1.0 mL every 4 weeks for a total of six doses. | 89 |
| Reslizumab 110 mg Reslizumab was administered by subcutaneous injection (sc) in a dosage of 110 mg (1.0 mL) every 4 weeks for a total of six doses. | 88 |
| Total | 177 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
| Overall Study | Early termination by sponsor | 1 | 0 |
| Overall Study | Subject did not return to site | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 5 |
| Overall Study | Withdrawn from study by sponsor | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Reslizumab 110 mg | Total |
|---|---|---|---|
| Age, Continuous | 53.1 years STANDARD_DEVIATION 11.99 | 55.5 years STANDARD_DEVIATION 12.72 | 54.3 years STANDARD_DEVIATION 12.38 |
| Age Group 12 to <18 years | 1 Participants | 0 Participants | 1 Participants |
| Age Group 18 to <65 years | 74 Participants | 63 Participants | 137 Participants |
| Age Group >=65 years | 14 Participants | 25 Participants | 39 Participants |
| Body Mass Index | 29.859 kg/m^2 STANDARD_DEVIATION 6.3499 | 29.389 kg/m^2 STANDARD_DEVIATION 8.0105 | 29.625 kg/m^2 STANDARD_DEVIATION 7.2067 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants | 22 Participants | 38 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 72 Participants | 65 Participants | 137 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Oral Corticosteroid (OCS) Dose at Baseline | 10.37 mg STANDARD_DEVIATION 6.435 | 10.37 mg STANDARD_DEVIATION 6.807 | 10.37 mg STANDARD_DEVIATION 6.604 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants | 2 Participants | 5 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 4 Participants | 8 Participants | 12 Participants |
| Race/Ethnicity, Customized White | 80 Participants | 72 Participants | 152 Participants |
| Region Group Europe | 58 Participants | 47 Participants | 105 Participants |
| Region Group Other | 21 Participants | 32 Participants | 53 Participants |
| Region Group US/Canada | 10 Participants | 9 Participants | 19 Participants |
| Sex: Female, Male Female | 57 Participants | 60 Participants | 117 Participants |
| Sex: Female, Male Male | 32 Participants | 28 Participants | 60 Participants |
| Weight | 82.69 kg STANDARD_DEVIATION 18.949 | 79.58 kg STANDARD_DEVIATION 21.39 | 81.14 kg STANDARD_DEVIATION 20.202 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 89 | 1 / 88 |
| other Total, other adverse events | 20 / 89 | 20 / 88 |
| serious Total, serious adverse events | 4 / 89 | 10 / 88 |
Outcome results
Primary
Number of Participants With Reduction In Daily Oral Corticosteroid (OCS) Dose During Weeks 20-24 As Compared to the Optimized Dose At Baseline
The primary endpoint was the 5-level categorized percent reduction in OCS dose during weeks 20 to 24 compared with the optimized dose at baseline. The primary analysis incorporated data from all randomized patients. Analysis of the primary and secondary variables related to categorical OCS dose reduction incorporated missing data as non-responders. No decrease indicates there was no decrease in OCS, loss of baseline asthma control during weeks 20 to 24, or discontinuation from study drug.
Time frame: Baseline (Day 1), Weeks 20-24
Population: Intent to Treat (ITT) Analysis set; missing data are included as non-responders (no decrease).
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Reduction In Daily Oral Corticosteroid (OCS) Dose During Weeks 20-24 As Compared to the Optimized Dose At Baseline | No decrease | 48 Participants |
| Placebo | Number of Participants With Reduction In Daily Oral Corticosteroid (OCS) Dose During Weeks 20-24 As Compared to the Optimized Dose At Baseline | 90% to 100% | 20 Participants |
| Placebo | Number of Participants With Reduction In Daily Oral Corticosteroid (OCS) Dose During Weeks 20-24 As Compared to the Optimized Dose At Baseline | 75% to <90% | 4 Participants |
| Placebo | Number of Participants With Reduction In Daily Oral Corticosteroid (OCS) Dose During Weeks 20-24 As Compared to the Optimized Dose At Baseline | 50% to <75% | 8 Participants |
| Placebo | Number of Participants With Reduction In Daily Oral Corticosteroid (OCS) Dose During Weeks 20-24 As Compared to the Optimized Dose At Baseline | >0% to <50% | 9 Participants |
| Reslizumab 110 mg | Number of Participants With Reduction In Daily Oral Corticosteroid (OCS) Dose During Weeks 20-24 As Compared to the Optimized Dose At Baseline | >0% to <50% | 7 Participants |
| Reslizumab 110 mg | Number of Participants With Reduction In Daily Oral Corticosteroid (OCS) Dose During Weeks 20-24 As Compared to the Optimized Dose At Baseline | 50% to <75% | 13 Participants |
| Reslizumab 110 mg | Number of Participants With Reduction In Daily Oral Corticosteroid (OCS) Dose During Weeks 20-24 As Compared to the Optimized Dose At Baseline | 90% to 100% | 18 Participants |
| Reslizumab 110 mg | Number of Participants With Reduction In Daily Oral Corticosteroid (OCS) Dose During Weeks 20-24 As Compared to the Optimized Dose At Baseline | No decrease | 42 Participants |
| Reslizumab 110 mg | Number of Participants With Reduction In Daily Oral Corticosteroid (OCS) Dose During Weeks 20-24 As Compared to the Optimized Dose At Baseline | 75% to <90% | 8 Participants |
Comparison: The proportional odds ratio (reslizumab/placebo) was estimated from this model, representing the ratio of the odds of a patient outcome being in a higher OCS dose reduction category for reslizumab compared to placebo.p-value: 0.46895% CI: [0.702, 2.157]proportional odds model
Secondary
Annualized Rate of Clinical Asthma Exacerbations (CAEs)
The annual exacerbation rate is based on clinical asthma exacerbations reported by the investigator in the eCRF.
Time frame: Day 1 through Week 24
Population: ITT Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Annualized Rate of Clinical Asthma Exacerbations (CAEs) | 1.86 CAEs / year |
| Reslizumab 110 mg | Annualized Rate of Clinical Asthma Exacerbations (CAEs) | 1.51 CAEs / year |
p-value: 0.40795% CI: [0.504, 1.321]Negative binomial regression model
Secondary
Participants With Adverse Events
An adverse event is any untoward medical occurrence in a patient administered a pharmaceutical product, regardless of whether it has a causal relationship with this treatment. In this study, asthma exacerbations (which are efficacy parameters) should not be recorded as adverse events unless assessed by the investigator as more severe than the patient's usual disease course. Relation of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes. Treatment-related adverse events or adverse events related to OCS use included events with missing relationship to study drug or OCS use, respectively.
Time frame: Day 1 up to Week 24 (end of treatment visit); Data were included between Day 1 and Week 24 for completed patients, and Day 1 and 4 weeks after the last dose of study drug for patients who discontinued treatment early.
Population: Safety analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Participants With Adverse Events | Any AE | 47 Participants |
| Placebo | Participants With Adverse Events | Treatment-related AE | 3 Participants |
| Placebo | Participants With Adverse Events | Serious AE (SAE) | 4 Participants |
| Placebo | Participants With Adverse Events | Treatment-related SAE | 0 Participants |
| Placebo | Participants With Adverse Events | SAE resulting in death | 0 Participants |
| Placebo | Participants With Adverse Events | AE leading to treatment discontinuation | 1 Participants |
| Placebo | Participants With Adverse Events | AE related to OCS withdrawal | 2 Participants |
| Placebo | Participants With Adverse Events | AE related to OCS use | 2 Participants |
| Reslizumab 110 mg | Participants With Adverse Events | AE related to OCS use | 5 Participants |
| Reslizumab 110 mg | Participants With Adverse Events | Any AE | 57 Participants |
| Reslizumab 110 mg | Participants With Adverse Events | SAE resulting in death | 1 Participants |
| Reslizumab 110 mg | Participants With Adverse Events | Treatment-related AE | 7 Participants |
| Reslizumab 110 mg | Participants With Adverse Events | AE related to OCS withdrawal | 3 Participants |
| Reslizumab 110 mg | Participants With Adverse Events | Serious AE (SAE) | 10 Participants |
| Reslizumab 110 mg | Participants With Adverse Events | AE leading to treatment discontinuation | 0 Participants |
| Reslizumab 110 mg | Participants With Adverse Events | Treatment-related SAE | 0 Participants |
Secondary
Participants With Treatment-Emergent Anti-Drug Antibody (ADA) Responses
Treatment-emergent responses were defined as a positive sample post-baseline (negative baseline) OR a titer increase of \>=4-fold relative to a positive baseline sample. Two types of antibody assay were performed, an immunogenicity status assay (ADA) and neutralizing assay (NAb). The ADA assay produces a positive or negative result. For samples with a positive result, a neutralizing assay was performed, which also produces a positive or negative result.
Time frame: Weeks 4, 8, 12, 24 or early withdrawal.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Participants With Treatment-Emergent Anti-Drug Antibody (ADA) Responses | Positive ADA samples | 0 Participants |
| Placebo | Participants With Treatment-Emergent Anti-Drug Antibody (ADA) Responses | Positive Nab samples | 0 Participants |
| Reslizumab 110 mg | Participants With Treatment-Emergent Anti-Drug Antibody (ADA) Responses | Positive ADA samples | 11 Participants |
| Reslizumab 110 mg | Participants With Treatment-Emergent Anti-Drug Antibody (ADA) Responses | Positive Nab samples | 0 Participants |
Secondary
Percentage of Participants Achieving a >=50% Reduction in OCS Dose at Weeks 20-24 Compared to Baseline While Maintaining Asthma Control
Percentage of patients whose OCS dose at weeks 20-24 was reduced \>=50% compared to baseline while maintaining asthma control. Patients listed as no did not achieve the 50% reduction in baseline OCS dose goal, or did achieve that goal but lost asthma control during weeks 20 to 24, or discontinued from study drug.
Time frame: Baseline (Day 1), Weeks 20-24
Population: ITT Analysis set; missing data are included as non-responders (No).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Achieving a >=50% Reduction in OCS Dose at Weeks 20-24 Compared to Baseline While Maintaining Asthma Control | Yes | 36 percentage of participants |
| Placebo | Percentage of Participants Achieving a >=50% Reduction in OCS Dose at Weeks 20-24 Compared to Baseline While Maintaining Asthma Control | No | 64 percentage of participants |
| Reslizumab 110 mg | Percentage of Participants Achieving a >=50% Reduction in OCS Dose at Weeks 20-24 Compared to Baseline While Maintaining Asthma Control | Yes | 44 percentage of participants |
| Reslizumab 110 mg | Percentage of Participants Achieving a >=50% Reduction in OCS Dose at Weeks 20-24 Compared to Baseline While Maintaining Asthma Control | No | 56 percentage of participants |
Comparison: As the analysis of the primary efficacy endpoint did not meet criteria for statistical significance (p≤0.05), the secondary efficacy endpoints were not interpreted inferentially according to the pre-defined hierarchy. P-values are nominal, meaning they were obtained from the analysis without adjustments to protect family-wise errors and should be interpreted with caution. Nominal p-values do not indicate treatment differences.p-value: 0.23495% CI: [0.786, 2.683]Regression, Logistic
Secondary
Percentage of Participants Achieving a >=5 mg Reduction in OCS Dose at Weeks 20-24 Compared to Baseline While Maintaining Asthma Control
Percentage of participants whose OCS dose at weeks 20-24 was reduced by at least 5mg from baseline and maintained asthma control. Patients listed as no had a week 20-24 OCS dose that did not meet the threshold of a 5mg reduction, or whose OCS dose met the threshold but did not maintain asthma control, or discontinued from study drug.
Time frame: Baseline (Day 1), Weeks 20-24
Population: ITT Analysis set; missing data are included as non-responders (No).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Achieving a >=5 mg Reduction in OCS Dose at Weeks 20-24 Compared to Baseline While Maintaining Asthma Control | Yes | 35 percentage of participants |
| Placebo | Percentage of Participants Achieving a >=5 mg Reduction in OCS Dose at Weeks 20-24 Compared to Baseline While Maintaining Asthma Control | No | 65 percentage of participants |
| Reslizumab 110 mg | Percentage of Participants Achieving a >=5 mg Reduction in OCS Dose at Weeks 20-24 Compared to Baseline While Maintaining Asthma Control | Yes | 41 percentage of participants |
| Reslizumab 110 mg | Percentage of Participants Achieving a >=5 mg Reduction in OCS Dose at Weeks 20-24 Compared to Baseline While Maintaining Asthma Control | No | 59 percentage of participants |
Comparison: As the analysis of the primary efficacy endpoint did not meet criteria for statistical significance (p≤0.05), the secondary efficacy endpoints were not interpreted inferentially according to the pre-defined hierarchy. P-values are nominal, meaning they were obtained from the analysis without adjustments to protect family-wise errors and should be interpreted with caution. Nominal p-values do not indicate treatment differences.p-value: 0.34195% CI: [0.722, 2.562]Regression, Logistic
Secondary
Percentage of Participants Achieving an OCS Dose of 0 mg at Weeks 20-24 While Maintaining Asthma Control
Percentage of participants who discontinue use of OCS during weeks 20-24 while maintaining asthma control. Patients listed as no continued to use OCS during weeks 20-24, or who discontinued use of OCS during weeks 20-24 but lost control of their asthma, or discontinued from study drug.
Time frame: Weeks 20-24
Population: ITT Analysis set; missing data are included as non-responders (No).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Achieving an OCS Dose of 0 mg at Weeks 20-24 While Maintaining Asthma Control | Yes | 22 percentage of participants |
| Placebo | Percentage of Participants Achieving an OCS Dose of 0 mg at Weeks 20-24 While Maintaining Asthma Control | No | 78 percentage of participants |
| Reslizumab 110 mg | Percentage of Participants Achieving an OCS Dose of 0 mg at Weeks 20-24 While Maintaining Asthma Control | Yes | 20 percentage of participants |
| Reslizumab 110 mg | Percentage of Participants Achieving an OCS Dose of 0 mg at Weeks 20-24 While Maintaining Asthma Control | No | 80 percentage of participants |
Comparison: As the analysis of the primary efficacy endpoint did not meet criteria for statistical significance (p≤0.05), the secondary efficacy endpoints were not interpreted inferentially according to the pre-defined hierarchy. P-values are nominal, meaning they were obtained from the analysis without adjustments to protect family-wise errors and should be interpreted with caution. Nominal p-values do not indicate treatment differences.p-value: 0.62895% CI: [0.371, 1.818]Regression, Logistic
Secondary
Percentage of Participants Achieving an OCS Dose of <=5 mg at Weeks 20-24 While Maintaining Asthma Control
Percentage of participants whose OCS dose at weeks 20-24 was \<=5 mg and they maintained asthma control. Patients listed as no had a week 20-24 OCS dose \> 5 mg, or whose OCS dose was \<=5 mg at weeks 20-24 but did not maintain asthma control, or they discontinued from study drug.
Time frame: Weeks 20-24
Population: ITT Analysis set; missing data are included as non-responders (No).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Achieving an OCS Dose of <=5 mg at Weeks 20-24 While Maintaining Asthma Control | No | 62 percentage of participants |
| Placebo | Percentage of Participants Achieving an OCS Dose of <=5 mg at Weeks 20-24 While Maintaining Asthma Control | Yes | 38 percentage of participants |
| Reslizumab 110 mg | Percentage of Participants Achieving an OCS Dose of <=5 mg at Weeks 20-24 While Maintaining Asthma Control | Yes | 42 percentage of participants |
| Reslizumab 110 mg | Percentage of Participants Achieving an OCS Dose of <=5 mg at Weeks 20-24 While Maintaining Asthma Control | No | 58 percentage of participants |
Comparison: As the analysis of the primary efficacy endpoint did not meet criteria for statistical significance (p≤0.05), the secondary efficacy endpoints were not interpreted inferentially according to the pre-defined hierarchy. P-values are nominal, meaning they were obtained from the analysis without adjustments to protect family-wise errors and should be interpreted with caution. Nominal p-values do not indicate treatment differences.p-value: 0.59695% CI: [0.631, 2.229]Regression, Logistic
Secondary
Percent Change From Baseline in Daily Oral Corticosteroid (OCS) Dose During Weeks 20-24 Using a Mixed Model for Repeated Measures
The baseline OCS dose is the prescribed optimized OCS dose following the OCS optimization period. Endpoint data are presented using an on-treatment approach. In this context, 'endpoint' was defined as the last observation obtained at a scheduled or qualified early termination visit during the treatment period. Weeks 20-24 data is included between the Week 20 dose and Week 24 for completed patients; last dose of study drug to 4 weeks after the last dose of study drug for patients who discontinued treatment early. Measurements collected outside of these defined timeframes are excluded from the analyses. The mixed model repeated measures (MMRM) included fixed effects for treatment, visit, treatment by visit interaction, age group, and OCS dose group, duration of OCS use and baseline value as covariates, and patient as a random effect. Unstructured covariance was assumed for the repeated measures.
Time frame: Baseline (Day 1), Weeks 20-24
Population: ITT analysis population with available data using the on-treatment approach.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change From Baseline in Daily Oral Corticosteroid (OCS) Dose During Weeks 20-24 Using a Mixed Model for Repeated Measures | -40.34 percent change | Standard Error 17.318 |
| Reslizumab 110 mg | Percent Change From Baseline in Daily Oral Corticosteroid (OCS) Dose During Weeks 20-24 Using a Mixed Model for Repeated Measures | -58.08 percent change | Standard Error 17.633 |
Comparison: Mixed model repeated measures (MMRM) with fixed effects for treatment, visit, treatment by visit interaction, age group, and OCS dose group, duration of OCS use and baseline value as covariates, and patient as a random effect. Unstructured covariance was assumed for the repeated measures.p-value: 0.10195% CI: [-38.986, 3.494]mixed model repeated measures (MMRM)