An Efficacy and Safety Study of Reslizumab Subcutaneous in Patients With Oral Corticosteroid Dependent Asthma and Elevated Blood Eosinophils

Phase 3

Completed

Conditions: Elevated Blood Eosinophils
Oral Corticosteroid Dependence
Asthma

Interventions: Drug: Reslizumab
Drug: Placebo
Drug: Non-Oral Corticosteroid (non-OCS) Asthma Medication
Drug: Oral Corticosteroid (OCS)

Registration Number: NCT02501629

Lead Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 177

Inclusion Criteria

The patient is male or female, 12 years of age and older, with a previous diagnosis of asthma.
Written informed consent is obtained.
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.
The patient has a documented elevated blood eosinophils at screening or during the previous 12 months.
The patient has required high dose ICS plus another asthma controller for at least 6 months prior to screening.
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

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.
The patient has another confounding underlying lung disorder.
The patient has a known hypereosinophilic syndrome.
The patient has a history of any malignancy within 5 years of the screening visit, except for treated and cured non-melanoma skin cancers.
The patient is pregnant or intends to become pregnant during the study or is lactating.
The patient required treatment for an asthma exacerbation within 4 weeks of screening.
The patient is a current smoker or has a smoking history ≥10 pack-years.
The patient is currently using any systemic immunosuppressive or immunomodulatory biologic except maintenance OCS for the treatment of asthma.
The patient participated in a clinical study within 30 days or 5 half-lives of the investigational drug before screening, whichever is longer.
The patient was previously exposed to benralizumab within 12 months of screening.
The patient was previously exposed to reslizumab.
The patient has a history of immunodeficiency disorder including human immunodeficiency virus.
The patient has current suspected drug and/or alcohol abuse.
The patient has had an active helminthic parasitic infection or was treated for one within 6 months of screening.
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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Reslizumab 110 mg	Reslizumab	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.
Reslizumab 110 mg	Non-Oral Corticosteroid (non-OCS) Asthma Medication	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.
Reslizumab 110 mg	Oral Corticosteroid (OCS)	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.
Placebo	Placebo	Matching placebo was administered by subcutaneous injection (sc) 1.0 mL every 4 weeks for a total of six doses.
Placebo	Non-Oral Corticosteroid (non-OCS) Asthma Medication	Matching placebo was administered by subcutaneous injection (sc) 1.0 mL every 4 weeks for a total of six doses.
Placebo	Oral Corticosteroid (OCS)	Matching placebo was administered by subcutaneous injection (sc) 1.0 mL every 4 weeks for a total of six doses.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.
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 <=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.

Trial Locations

Locations (127): Teva Investigational Site 13349
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Cincinnati, Ohio, United States
Teva Investigational Site 13357
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Bakersfield, California, United States
Teva Investigational Site 13365
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Long Beach, California, United States
Teva Investigational Site 13371
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Clermont, Florida, United States
Teva Investigational Site 13342
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Kissimmee, Florida, United States
Teva Investigational Site 13344
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Miami, Florida, United States
Teva Investigational Site 13372
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Miami, Florida, United States
Teva Investigational Site 13354
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Pembroke Pines, Florida, United States
Teva Investigational Site 13343
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Saint Cloud, Florida, United States
Teva Investigational Site 13368
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Sebring, Florida, United States
Teva Investigational Site 13363
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Normal, Illinois, United States
Teva Investigational Site 13367
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Chicago, Illinois, United States
Teva Investigational Site 13350
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Saint Louis, Missouri, United States
Teva Investigational Site 13370
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Edmond, Oklahoma, United States
Teva Investigational Site 13356
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New York, New York, United States
Teva Investigational Site 13369
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Houston, Texas, United States
Teva Investigational Site 13358
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Fairfax, Virginia, United States
Teva Investigational Site 13377
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Dallas, Texas, United States
Teva Investigational Site 20059
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Buenos Aires, Argentina
Teva Investigational Site 20056
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Buenos Aires, Argentina
Teva Investigational Site 20057
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Buenos Aires, Argentina
Teva Investigational Site 20052
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Cordoba, Argentina
Teva Investigational Site 20055
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Mendoza, Argentina
Teva Investigational Site 20087
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Rosario, Argentina
Teva Investigational Site 20051
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San Miguel de Tucuman, Argentina
Teva Investigational Site 20050
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Mendoza, Argentina
Teva Investigational Site 20066
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San Rafael, Argentina
Teva Investigational Site 78092
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Box Hill, Australia
Teva Investigational Site 37059
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Bruxelles, Belgium
Teva Investigational Site 78093
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Kent Town, Australia
Teva Investigational Site 78089
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Bedford Park, Australia
Teva Investigational Site 78097
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Frankston, Australia
Teva Investigational Site 78090
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Nedlands, Australia
Teva Investigational Site 54133
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Breclav, Czechia
Teva Investigational Site 37058
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Gembloux, Belgium
Teva Investigational Site 78091
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New Lambton, Australia
Teva Investigational Site 35186
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Le Kremlin-bicetre, France
Teva Investigational Site 54132
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Jindrichuv Hradec, Czechia
Teva Investigational Site 35185
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Lille Cedex, France
Teva Investigational Site 35189
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Lyon Cedex 04, France
Teva Investigational Site 35187
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Strasbourg, France
Teva Investigational Site 32621
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Bad Worishofen, Germany
Teva Investigational Site 32573
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Berlin, Germany
Teva Investigational Site 32578
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Berlin, Germany
Teva Investigational Site 32576
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Berlin, Germany
Teva Investigational Site 32622
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Frankfurt, Germany
Teva Investigational Site 32579
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Hannover, Germany
Teva Investigational Site 32574
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Leipzig, Germany
Teva Investigational Site 51253
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Szombathely, Hungary
Teva Investigational Site 32580
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Rostock, Germany
Teva Investigational Site 51232
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Dombovar, Hungary
Teva Investigational Site 80085
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Haifa, Israel
Teva Investigational Site 51254
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Csorna, Hungary
Teva Investigational Site 51233
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Hatvan, Hungary
Teva Investigational Site 80091
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Kfar Saba, Israel
Teva Investigational Site 80083
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Jerusalem, Israel
Teva Investigational Site 80084
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Petah Tikva, Israel
Teva Investigational Site 30152
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Catanzaro, Italy
Teva Investigational Site 87020
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Goyang-si, Korea, Republic of
Teva Investigational Site 87023
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Seoul, Korea, Republic of
Teva Investigational Site 21102
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Distrito Federal, Mexico
Teva Investigational Site 21106
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Chihuahua, Mexico
Teva Investigational Site 87021
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Seoul, Korea, Republic of
Teva Investigational Site 21104
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Durango, Mexico
Teva Investigational Site 21094
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Guadalajara, Mexico
Teva Investigational Site 21100
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Guadalajara, Mexico
Teva Investigational Site 21093
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Guadalajara, Mexico
Teva Investigational Site 21090
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Mexico City, Mexico
Teva Investigational Site 21103
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Monterrey, Mexico
Teva Investigational Site 21101
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Monterrey, Mexico
Teva Investigational Site 21105
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Queretaro, Mexico
Teva Investigational Site 53316
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Gdansk, Poland
Teva Investigational Site 53319
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Lodz, Poland
Teva Investigational Site 38084
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Leeuwarden, Netherlands
Teva Investigational Site 53318
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Krakow, Poland
Teva Investigational Site 53321
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Lodz, Poland
Teva Investigational Site 53322
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Lubin, Poland
Teva Investigational Site 53358
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Rzeszow, Poland
Teva Investigational Site 53320
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Ostrow Wielkopolski, Poland
Teva Investigational Site 50356
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Barnaul, Russian Federation
Teva Investigational Site 53323
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Wroclaw, Poland
Teva Investigational Site 50417
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Chelyabinsk, Russian Federation
Teva Investigational Site 53317
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Tarnow, Poland
Teva Investigational Site 50419
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Ekaterinburg, Russian Federation
Teva Investigational Site 50385
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Kemerovo, Russian Federation
Teva Investigational Site 50382
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Kemerovo, Russian Federation
Teva Investigational Site 50383
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Novosibirsk, Russian Federation
Teva Investigational Site 50357
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St. Petersburg, Russian Federation
Teva Investigational Site 50384
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Moscow, Russian Federation
Teva Investigational Site 50386
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Novosibirsk, Russian Federation
Teva Investigational Site 50418
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Tomsk, Russian Federation
Teva Investigational Site 31161
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Girona, Spain
Teva Investigational Site 31159
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Barcelona, Spain
Teva Investigational Site 31160
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Valencia, Spain
Teva Investigational Site 31158
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Valencia, Spain
Teva Investigational Site 58245
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Dnepropetrovsk, Ukraine
Teva Investigational Site 58244
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Kharkiv, Ukraine
Teva Investigational Site 58238
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Dnipropetrovsk, Ukraine
Teva Investigational Site 58241
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Kharkiv, Ukraine
Teva Investigational Site 58249
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Kremenchuk, Ukraine
Teva Investigational Site 58239
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Kharkiv, Ukraine
Teva Investigational Site 58235
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Kharkiv, Ukraine
Teva Investigational Site 58248
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Kyiv, Ukraine
Teva Investigational Site 58251
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Kyiv, Ukraine
Teva Investigational Site 58237
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Kyiv, Ukraine
Teva Investigational Site 58250
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Kyiv, Ukraine
Teva Investigational Site 58243
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Sumy, Ukraine
Teva Investigational Site 58246
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Vinnytsya, Ukraine
Teva Investigational Site 58242
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Zhaporizhzhya, Ukraine
Teva Investigational Site 13351
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Homestead, Florida, United States
Teva Investigational Site 13345
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Michigan City, Indiana, United States
Teva Investigational Site 13362
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Biloxi, Mississippi, United States
Teva Investigational Site 13348
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Lenexa, Kansas, United States
Teva Investigational Site 13352
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Saint Louis, Missouri, United States
Teva Investigational Site 20058
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Buenos Aires, Argentina
Teva Investigational Site 80082
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Rehovot, Israel
Teva Investigational Site 30154
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Genova, Italy
Teva Investigational Site 87024
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Jeonju, Korea, Republic of
Teva Investigational Site 87025
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Seongnam-si, Korea, Republic of
Teva Investigational Site 87022
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Seoul, Korea, Republic of
Teva Investigational Site 21091
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Guadalajara, Mexico
Teva Investigational Site 38085
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Zwolle, Netherlands
Teva Investigational Site 50358
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Tomsk, Russian Federation
Teva Investigational Site 58240
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Ivano-Frankivsk, Ukraine
Teva Investigational Site 13346
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Tampa, Florida, United States
Teva Investigational Site 13347
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Oklahoma City, Oklahoma, United States
Teva Investigational Site 13366
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Charleston, South Carolina, United States