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

Asthma Clinical Trial

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02501629
• Other study ID #: C38072-AS-30027
• Secondary ID: 2015-001580-39
• Status: Completed
• Phase: Phase 3
• Start date: September 29, 2015
• Est. completion date: December 4, 2017

Study information

• Verified date: November 2021
• Source: Teva Branded Pharmaceutical Products R&D, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 177
• Est. completion date: December 4, 2017
• Est. primary completion date: June 19, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Asthma
• Elevated Blood Eosinophils
• Oral Corticosteroid Dependence

Intervention

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.
• 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.
• Non-Oral Corticosteroid (non-OCS) Asthma Medication
Participants continue using their non-OCS background asthma medications without change during the study's treatment period.
• Oral Corticosteroid (OCS)
After screening and prior to study start, the participant's OCS dose was adjusted to determine the minimal effective OCS requirement.

Locations

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

Sponsors (1)

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

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Czechia,  France,  Germany,  Hungary,  Israel,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  Poland,  Russian Federation,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Baseline (Day 1), Weeks 20-24
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.	Baseline (Day 1), Weeks 20-24
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.	Weeks 20-24
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.	Baseline (Day 1), Weeks 20-24
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.	Baseline (Day 1), Weeks 20-24
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.	Day 1 through Week 24
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.	Weeks 20-24
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.	Weeks 4, 8, 12, 24 or early withdrawal.
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.	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.