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

A Phase 3, 24-Week Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy and Safety Study of Reslizumab Subcutaneous Dosing (110 mg Every 4 Weeks) in Patients With Oral Corticosteroid Dependent Asthma and Elevated Blood Eosinophils

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.

Study Overview

• Status: Completed
• Conditions: Asthma; Elevated Blood Eosinophils; Oral Corticosteroid Dependence
• Intervention / Treatment: Drug: Reslizumab; Drug: Non-Oral Corticosteroid (non-OCS) Asthma Medication; Drug: Oral Corticosteroid (OCS); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 177
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1028AAP
    • Teva Investigational Site 20059
  • Buenos Aires, Argentina, C1425BEN
    • Teva Investigational Site 20058
  • Buenos Aires, Argentina, C1426ABP
    • Teva Investigational Site 20056
  • Buenos Aires, Argentina
    • Teva Investigational Site 20057
  • Cordoba, Argentina, X5003DCE
    • Teva Investigational Site 20052
  • Mendoza, Argentina, 5500
    • Teva Investigational Site 20055
  • Mendoza, Argentina, M5500CCG
    • Teva Investigational Site 20050
  • Rosario, Argentina, 2000
    • Teva Investigational Site 20087
  • San Miguel de Tucuman, Argentina, T4000CHE
    • Teva Investigational Site 20051
  • San Rafael, Argentina
    • Teva Investigational Site 20066
• Australia
  • Bedford Park, Australia, 5042
    • Teva Investigational Site 78089
  • Box Hill, Australia, 3128
    • Teva Investigational Site 78092
  • Frankston, Australia, 3199
    • Teva Investigational Site 78097
  • Kent Town, Australia, 5067
    • Teva Investigational Site 78093
  • Nedlands, Australia, 6009
    • Teva Investigational Site 78090
  • New Lambton, Australia, 2305
    • Teva Investigational Site 78091
• Belgium
  • Bruxelles, Belgium, 1200
    • Teva Investigational Site 37059
  • Gembloux, Belgium, 5030
    • Teva Investigational Site 37058
• Czechia
  • Breclav, Czechia, 690 74
    • Teva Investigational Site 54133
  • Jindrichuv Hradec, Czechia, 377 38
    • Teva Investigational Site 54132
• France
  • Le Kremlin-bicetre, France, 94275 Cedex
    • Teva Investigational Site 35186
  • Lille Cedex, France, 59037
    • Teva Investigational Site 35185
  • Lyon Cedex 04, France, 69317
    • Teva Investigational Site 35189
  • Strasbourg, France, 67091
    • Teva Investigational Site 35187
• Germany
  • Bad Worishofen, Germany, 86825
    • Teva Investigational Site 32621
  • Berlin, Germany, 10717
    • Teva Investigational Site 32576
  • Berlin, Germany, 12159
    • Teva Investigational Site 32573
  • Berlin, Germany, 13187
    • Teva Investigational Site 32578
  • Frankfurt, Germany, 60389
    • Teva Investigational Site 32622
  • Hannover, Germany, 30173
    • Teva Investigational Site 32579
  • Leipzig, Germany, 4275
    • Teva Investigational Site 32574
  • Rostock, Germany, 18057
    • Teva Investigational Site 32580
• Hungary
  • Csorna, Hungary, 9300
    • Teva Investigational Site 51254
  • Dombovar, Hungary, 7200
    • Teva Investigational Site 51232
  • Hatvan, Hungary, 3000
    • Teva Investigational Site 51233
  • Szombathely, Hungary, 9700
    • Teva Investigational Site 51253
• Israel
  • Haifa, Israel, 3436212
    • Teva Investigational Site 80085
  • Jerusalem, Israel, 91120
    • Teva Investigational Site 80083
  • Kfar Saba, Israel, 44281
    • Teva Investigational Site 80091
  • Petah Tikva, Israel, 49100
    • Teva Investigational Site 80084
  • Rehovot, Israel, 76100
    • Teva Investigational Site 80082
• Italy
  • Catanzaro, Italy, 88100
    • Teva Investigational Site 30152
  • Genova, Italy, 16132
    • Teva Investigational Site 30154
• Korea, Republic of
  • Goyang-si, Korea, Republic of, 411-706
    • Teva Investigational Site 87020
  • Jeonju, Korea, Republic of, 561-712
    • Teva Investigational Site 87024
  • Seongnam-si, Korea, Republic of, 463-707
    • Teva Investigational Site 87025
  • Seoul, Korea, Republic of, 137-701
    • Teva Investigational Site 87023
  • Seoul, Korea, Republic of, 138-736
    • Teva Investigational Site 87022
  • Seoul, Korea, Republic of, 143-729
    • Teva Investigational Site 87021
• Mexico
  • Chihuahua, Mexico, 31203
    • Teva Investigational Site 21106
  • Distrito Federal, Mexico, 07020
    • Teva Investigational Site 21102
  • Durango, Mexico, 34080
    • Teva Investigational Site 21104
  • Guadalajara, Mexico, 44100
    • Teva Investigational Site 21094
  • Guadalajara, Mexico, 44130
    • Teva Investigational Site 21091
  • Guadalajara, Mexico, 44160
    • Teva Investigational Site 21100
  • Guadalajara, Mexico, 44220
    • Teva Investigational Site 21093
  • Mexico City, Mexico, 06700
    • Teva Investigational Site 21090
  • Monterrey, Mexico, 64460
    • Teva Investigational Site 21103
  • Monterrey, Mexico, 64718
    • Teva Investigational Site 21101
  • Queretaro, Mexico, 76800
    • Teva Investigational Site 21105
• Netherlands
  • Leeuwarden, Netherlands, 8901 BR
    • Teva Investigational Site 38084
  • Zwolle, Netherlands, 8025-AB
    • Teva Investigational Site 38085
• Poland
  • Gdansk, Poland, 80-952
    • Teva Investigational Site 53316
  • Krakow, Poland, 31-624
    • Teva Investigational Site 53318
  • Lodz, Poland, 90-153
    • Teva Investigational Site 53319
  • Lodz, Poland, 90-153
    • Teva Investigational Site 53321
  • Lubin, Poland, 59-300
    • Teva Investigational Site 53322
  • Ostrow Wielkopolski, Poland, 63-400
    • Teva Investigational Site 53320
  • Rzeszow, Poland, 35-612
    • Teva Investigational Site 53358
  • Tarnow, Poland, 33-100
    • Teva Investigational Site 53317
  • Wroclaw, Poland, 54-239
    • Teva Investigational Site 53323
• Russian Federation
  • Barnaul, Russian Federation, 656024
    • Teva Investigational Site 50356
  • Chelyabinsk, Russian Federation, 454021
    • Teva Investigational Site 50417
  • Ekaterinburg, Russian Federation, 620039
    • Teva Investigational Site 50419
  • Kemerovo, Russian Federation, 650002
    • Teva Investigational Site 50385
  • Kemerovo, Russian Federation, 650099
    • Teva Investigational Site 50382
  • Moscow, Russian Federation, 129090
    • Teva Investigational Site 50384
  • Novosibirsk, Russian Federation, 630091
    • Teva Investigational Site 50383
  • Novosibirsk, Russian Federation, 630099
    • Teva Investigational Site 50386
  • St. Petersburg, Russian Federation, 197089
    • Teva Investigational Site 50357
  • Tomsk, Russian Federation, 634050
    • Teva Investigational Site 50418
  • Tomsk, Russian Federation, 634063
    • Teva Investigational Site 50358
• Spain
  • Barcelona, Spain, ?08025
    • Teva Investigational Site 31159
  • Girona, Spain, 17004
    • Teva Investigational Site 31161
  • Valencia, Spain, 46017
    • Teva Investigational Site 31160
  • Valencia, Spain, 46026
    • Teva Investigational Site 31158
• Ukraine
  • Dnepropetrovsk, Ukraine, 49044
    • Teva Investigational Site 58245
  • Dnipropetrovsk, Ukraine, 49074
    • Teva Investigational Site 58238
  • Ivano-Frankivsk, Ukraine, 76018
    • Teva Investigational Site 58240
  • Kharkiv, Ukraine, 61002
    • Teva Investigational Site 58244
  • Kharkiv, Ukraine, 61007
    • Teva Investigational Site 58235
  • Kharkiv, Ukraine, 61035
    • Teva Investigational Site 58239
  • Kharkiv, Ukraine, 61039
    • Teva Investigational Site 58241
  • Kremenchuk, Ukraine, 39617
    • Teva Investigational Site 58249
  • Kyiv, Ukraine, 03680
    • Teva Investigational Site 58248
  • Kyiv, Ukraine, 2091
    • Teva Investigational Site 58251
  • Kyiv, Ukraine, 3049
    • Teva Investigational Site 58237
  • Kyiv, Ukraine, ?03680
    • Teva Investigational Site 58250
  • Sumy, Ukraine, 40022
    • Teva Investigational Site 58243
  • Vinnytsya, Ukraine, 21001
    • Teva Investigational Site 58246
  • Zhaporizhzhya, Ukraine, 69035
    • Teva Investigational Site 58242
• United States
  • California
    • Bakersfield, California, United States, 93301
      • Teva Investigational Site 13357
    • Long Beach, California, United States, 90813
      • Teva Investigational Site 13365
  • Florida
    • Clermont, Florida, United States, 73034
      • Teva Investigational Site 13371
    • Homestead, Florida, United States, 33030
      • Teva Investigational Site 13351
    • Kissimmee, Florida, United States, 34741
      • Teva Investigational Site 13342
    • Miami, Florida, United States, 33015
      • Teva Investigational Site 13344
    • Miami, Florida, United States, 33133
      • Teva Investigational Site 13372
    • Pembroke Pines, Florida, United States, 33029
      • Teva Investigational Site 13354
    • Saint Cloud, Florida, United States, 34769
      • Teva Investigational Site 13343
    • Sebring, Florida, United States, 33870
      • Teva Investigational Site 13368
    • Tampa, Florida, United States, 33607
      • Teva Investigational Site 13346
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Teva Investigational Site 13367
    • Normal, Illinois, United States, 61761
      • Teva Investigational Site 13363
  • Indiana
    • Michigan City, Indiana, United States, 46360
      • Teva Investigational Site 13345
  • Kansas
    • Lenexa, Kansas, United States, 66215
      • Teva Investigational Site 13348
  • Mississippi
    • Biloxi, Mississippi, United States, 39531
      • Teva Investigational Site 13362
  • Missouri
    • Saint Louis, Missouri, United States, 63106
      • Teva Investigational Site 13350
    • Saint Louis, Missouri, United States, 63143
      • Teva Investigational Site 13352
  • New York
    • New York, New York, United States, 10016-9196
      • Teva Investigational Site 13356
  • Ohio
    • Cincinnati, Ohio, United States, 45231
      • Teva Investigational Site 13349
  • Oklahoma
    • Edmond, Oklahoma, United States, 73034
      • Teva Investigational Site 13370
    • Oklahoma City, Oklahoma, United States, 73112
      • Teva Investigational Site 13347
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Teva Investigational Site 13366
  • Texas
    • Dallas, Texas, United States, 75225
      • Teva Investigational Site 13377
    • Houston, Texas, United States, 77099
      • Teva Investigational Site 13369
  • Virginia
    • Fairfax, Virginia, United States, 22030
      • Teva Investigational Site 13358

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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.	Drug: Reslizumab; 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.; Other Names: CEP38072; Drug: Non-Oral Corticosteroid (non-OCS) Asthma Medication; Participants continue using their non-OCS background asthma medications without change during the study's treatment period.; Drug: Oral Corticosteroid (OCS); After screening and prior to study start, the participant's OCS dose was adjusted to determine the minimal effective OCS requirement.
PLACEBO_COMPARATOR: Placebo; Matching placebo was administered by subcutaneous injection (sc) 1.0 mL every 4 weeks for a total of six doses.	Drug: Non-Oral Corticosteroid (non-OCS) Asthma Medication; Participants continue using their non-OCS background asthma medications without change during the study's treatment period.; Drug: Oral Corticosteroid (OCS); After screening and prior to study start, the participant's OCS dose was adjusted to determine the minimal effective OCS requirement.; Drug: Placebo; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline (Day 1), Weeks 20-24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline (Day 1), Weeks 20-24
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.	Weeks 20-24
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.	Baseline (Day 1), Weeks 20-24
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.	Baseline (Day 1), Weeks 20-24
Annualized Rate of Clinical Asthma Exacerbations (CAEs)	The annual exacerbation rate is based on clinical asthma exacerbations reported by the investigator in the eCRF.	Day 1 through Week 24
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.	Weeks 20-24
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.	Weeks 4, 8, 12, 24 or early withdrawal.
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.	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.

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Bernstein JA, Virchow JC, Murphy K, Maspero JF, Jacobs J, Adir Y, Humbert M, Castro M, Marsteller DA, McElhattan J, Hickey L, Garin M, Vanlandingham R, Brusselle G. Effect of fixed-dose subcutaneous reslizumab on asthma exacerbations in patients with severe uncontrolled asthma and corticosteroid sparing in patients with oral corticosteroid-dependent asthma: results from two phase 3, randomised, double-blind, placebo-controlled trials. Lancet Respir Med. 2020 May;8(5):461-474. doi: 10.1016/S2213-2600(19)30372-8. Epub 2020 Feb 14.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 29, 2015
• Primary Completion (ACTUAL): June 19, 2017
• Study Completion (ACTUAL): December 4, 2017

Study Registration Dates

• First Submitted: July 14, 2015
• First Submitted That Met QC Criteria: July 15, 2015
• First Posted (ESTIMATE): July 17, 2015

Study Record Updates

• Last Update Posted (ACTUAL): November 9, 2021
• Last Update Submitted That Met QC Criteria: November 5, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Asthma; Reslizumab; Elevated Blood Eosinophils; Oral corticosteroid dependence
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Anti-Asthmatic Agents; Respiratory System Agents; Reslizumab
• Other Study ID Numbers: C38072-AS-30027; 2015-001580-39 (EUDRACT_NUMBER)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No