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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02501629




Registration number
NCT02501629
Ethics application status
Date submitted
14/07/2015
Date registered
17/07/2015
Date last updated
13/09/2018

Titles & IDs
Public title
An Efficacy and Safety Study of Reslizumab Subcutaneous in Patients With Oral Corticosteroid Dependent Asthma and Elevated Blood Eosinophils
Scientific title
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
Secondary ID [1] 0 0
2015-001580-39
Secondary ID [2] 0 0
C38072-AS-30027
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Asthma 0 0
Elevated Blood Eosinophils 0 0
Oral Corticosteroid Dependence 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Asthma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Reslizumab
Treatment: Drugs - Placebo
Treatment: Drugs - Non-Oral Corticosteroid (non-OCS) Asthma Medication
Treatment: Drugs - Oral Corticosteroid (OCS)

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.

Placebo Comparator: Placebo - Matching placebo was administered by subcutaneous injection (sc) 1.0 mL every 4 weeks for a total of six doses.


Treatment: Drugs: 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.

Treatment: Drugs: 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.

Treatment: Drugs: Non-Oral Corticosteroid (non-OCS) Asthma Medication
Participants continue using their non-OCS background asthma medications without change during the study's treatment period.

Treatment: Drugs: Oral Corticosteroid (OCS)
After screening and prior to study start, the participant's OCS dose was adjusted to determine the minimal effective OCS requirement.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline (Day 1), Weeks 20-24
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline (Day 1), Weeks 20-24
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Weeks 20-24
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
Baseline (Day 1), Weeks 20-24
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
Baseline (Day 1), Weeks 20-24
Secondary outcome [5] 0 0
Annualized Rate of Clinical Asthma Exacerbations (CAEs) - The annual exacerbation rate is based on clinical asthma exacerbations reported by the investigator in the eCRF.
Timepoint [5] 0 0
Day 1 through Week 24
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
Weeks 20-24
Secondary outcome [7] 0 0
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.
Timepoint [7] 0 0
Weeks 4, 8, 12, 24 or early withdrawal.
Secondary outcome [8] 0 0
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.
Timepoint [8] 0 0
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.

Eligibility
Key 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.
Minimum age
12 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Teva Investigational Site 78089 - Bedford Park
Recruitment hospital [2] 0 0
Teva Investigational Site 78092 - Box Hill
Recruitment hospital [3] 0 0
Teva Investigational Site 78097 - Frankston
Recruitment hospital [4] 0 0
Teva Investigational Site 78093 - Kent Town
Recruitment hospital [5] 0 0
Teva Investigational Site 78090 - Nedlands
Recruitment hospital [6] 0 0
Teva Investigational Site 78091 - New Lambton
Recruitment postcode(s) [1] 0 0
5042 - Bedford Park
Recruitment postcode(s) [2] 0 0
3128 - Box Hill
Recruitment postcode(s) [3] 0 0
3199 - Frankston
Recruitment postcode(s) [4] 0 0
5067 - Kent Town
Recruitment postcode(s) [5] 0 0
6009 - Nedlands
Recruitment postcode(s) [6] 0 0
2305 - New Lambton
Recruitment outside Australia
Country [1] 0 0
United States of America
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California
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Florida
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Illinois
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Indiana
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Kansas
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Mississippi
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Missouri
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New York
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Ohio
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Oklahoma
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South Carolina
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United States of America
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Texas
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United States of America
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Virginia
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Argentina
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Buenos Aires
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Argentina
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Cordoba
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Argentina
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Mendoza
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Rosario
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San Miguel de Tucuman
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Bruxelles
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Rostock
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Kfar Saba
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Tarnow
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Wroclaw
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Barnaul
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Kemerovo
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Moscow
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Novosibirsk
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St. Petersburg
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Tomsk
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Spain
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Barcelona
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Girona
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Valencia
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Ukraine
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Dnepropetrovsk
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Dnipropetrovsk
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Ukraine
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Ivano-Frankivsk
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Kharkiv
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Ukraine
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Kremenchuk
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Ukraine
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Kyiv
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Ukraine
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Sumy
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Ukraine
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Vinnytsya
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Ukraine
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Zhaporizhzhya

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Teva Branded Pharmaceutical Products R&D, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02501629
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Teva Medical Expert, MD
Address 0 0
Teva Pharmaceuticals USA
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications