A Study to Evaluate the Efficacy and Safety of Reslizumab (0.3 or 3.0 mg/kg) as Treatment for Patients (12-75 Years of Age) With Eosinophilic Asthma

Eosinophilic Asthma Clinical Trial

Official title:

A 16-Week, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Reslizumab (0.3 or 3.0 mg/kg) as Treatment for Patients (12-75 Years of Age) With Eosinophilic Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01270464
• Other study ID #: C38072/3081
• Secondary ID: 2010-023342-67
• Status: Completed
• Phase: Phase 3
• First received: December 29, 2010
• Last updated: May 23, 2014
• Start date: December 2010
• Est. completion date: December 2013

Study information

• Verified date: May 2014
• Source: Teva Pharmaceutical Industries
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationArgentina: Ministry of HealthBrazil: Ministry of HealthCanada: Health CanadaColombia: National Institutes of HealthFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Hungary: National Institute of PharmacyIsrael: Ministry of HealthMexico: Ministry of HealthNetherlands: Medicines Evaluation Board (MEB)Poland: Ministry of HealthRomania: National Medicines AgencySweden: Medical Products Agency
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to determine whether reslizumab, at a dosage of 0.3 or 3.0 mg/kg administered once every 4 weeks for a total of 4 doses, is more effective than placebo in improving lung function in patients with eosinophilic asthma.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 315
• Est. completion date: December 2013
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years to 75 Years

Eligibility

Inclusion Criteria:

• The patient is male or female, 12 through 75 years of age, with a previous diagnosis of asthma. Patients 12 through 17 years of age are excluded from participating in Argentina.

• The patient has an ACQ score of at least 1.5.

• The patient has airway reversibility of at least 12% to beta-agonist administration at screening.

• The patient is currently taking fluticasone at a dosage of at least 440 µg daily (or equivalent). Patients' baseline asthma therapy regimens (including but not limited to inhaled corticosteroids, leukotriene antagonists, 5-lipoxygenase inhibitors, cromolyn) must be stable for 30 days before screening, and continue without dosage changes throughout study.

• The patient has a blood eosinophil count of at least 400/µL.

• Female patients must be surgically sterile, 2 years postmenopausal, or must have a negative pregnancy test ßHCG at screening (serum) and baseline (urine).

• Female patients of childbearing potential (not surgically sterile or 2 years postmenopausal), must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for 30 days after the end-of-treatment visit. Acceptable methods of contraception include barrier method with spermicide, abstinence, intrauterine device (IUD), or steroidal contraceptive (oral, transdermal, implanted, and injected).

• Written informed consent is obtained. Patients 12 through 17 years old, where participating, need to provide assent in accordance with local standards.

• Other inclusion criteria apply.

Exclusion Criteria:

• The patient has a clinically meaningful comorbidity that would interfere with the study schedule or procedures, or compromise the patient's safety.

• The patient has known hypereosinophilic syndrome (HES).

• The patient has another confounding underlying lung disorder (eg, chronic obstructive pulmonary disease, pulmonary fibrosis, or lung cancer). The patient has other pulmonary conditions with symptoms of asthma and blood eosinophilia (eg, Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis).

• The patient is a current smoker (ie, has smoked within the last 6 months prior to screening).

• The patient has a history of use of systemic immunosuppressive or immunomodulating agents (anti-IgE mAb, methotrexate, cyclosporin, interferon-a, or anti-tumor necrosis factor mAb) within 6 months prior to study entry (screening).

• The patient is currently using systemic corticosteroids (includes use of oral corticosteroids).

• The patient has a current infection or disease that may preclude assessment of asthma.

• The patient is expected to be poorly compliant with study drug administration, study procedures, or visits.

• The patient has any aggravating factors that are inadequately controlled (eg, gastroesophageal reflux disease).

• The patient has participated in any investigative drug or device study within 30 days prior to screening.

• The patient has participated in any investigative biologics study within 90 days prior to screening.

• The patient has previously received anti-hIL-5 monoclonal antibody (eg, mepolizumab).

• Female patients who are pregnant, or nursing, or, if of childbearing potential and not using a medically accepted, effective method of birth control (e.g. spermicide, abstinence, IUD, or steroidal contraceptive [oral, transdermal, implanted, and injected]) are excluded from this study.

• The patient has a current infection or disease that may preclude assessment of asthma.

• The patient has a history of concurrent immunodeficiency (human immunodeficiency, acquired immunodeficiency syndrome, or congenital immunodeficiency). Patients in Argentina must have documented serology testing for HIV performed during screening.

• Other exclusion criteria apply.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma
• Eosinophilic Asthma
• Pulmonary Eosinophilia

Intervention

Drug:
• Reslizumab
0.3 mg/kg, 3.0 mg/kg
• Placebo
Matching placebo administered intravenously (iv) once every 4 weeks, for a total of 4 doses.

Locations

Country	Name	City	State
Argentina	Teva Investigational Site 121	Ciudad Autonoma de Buenos Aire
Argentina	Teva Investigational Site 126	Ciudad Autonoma de Buenos Aire
Argentina	Teva Investigational Site 127	Ciudad Autonoma de Buenos Aire
Argentina	Teva Investigational Site 128	Quilmes-Buenos Aires
Argentina	Teva Investigational Site 125	Rosario
Argentina	Teva Investigational Site 123	Rosario-Santa Fe
Argentina	Teva Investigational Site 120	San Miguel de Tucuman - Tucuma
Argentina	Teva Investigational Site 122	San Miguel de Tucuman - Tucuma
Argentina	Teva Investigational Site 124	San Miguel de Tucuman - Tucuma
Belgium	Teva Investigational Site 261	Bruxelles
Belgium	Teva Investigational Site 264	Bruxelles
Belgium	Teva Investigational Site 260	Gent
Belgium	Teva Investigational Site 263	Liège
Brazil	Teva Investigational Site 146	Belo Horizonte
Brazil	Teva Investigational Site 150	Florianopolis
Brazil	Teva Investigational Site 140	Porto Alegre
Brazil	Teva Investigational Site 143	Porto Alegre
Brazil	Teva Investigational Site 144	Porto Alegre
Brazil	Teva Investigational Site 145	Porto Alegre
Brazil	Teva Investigational Site 147	Porto Alegre - RS
Brazil	Teva Investigational Site 142	Santo André, São Paulo
Brazil	Teva Investigational Site 141	Sao Paulo
Canada	Teva Investigational Site 103	Calgary
Canada	Teva Investigational Site 101	Montreal
Canada	Teva Investigational Site 104	Newmarket
Canada	Teva Investigational Site 105	Windsor
Colombia	Teva Investigational Site 184	Bogota
Colombia	Teva Investigational Site 185	Bogota
Colombia	Teva Investigational Site 181	Bogotá
Colombia	Teva Investigational Site 182	Cali
Colombia	Teva Investigational Site 180	Floridablanca
Colombia	Teva Investigational Site 183	Medellin
France	Teva Investigational Site 343	Grenoble
France	Teva Investigational Site 342	Marseille
France	Teva Investigational Site 341	Montpellier
France	Teva Investigational Site 340	Nantes
France	Teva Investigational Site 344	Pessac
Hungary	Teva Investigational Site 401	Balassagyarmat
Hungary	Teva Investigational Site 406	Edelény
Hungary	Teva Investigational Site 400	Miskolc
Hungary	Teva Investigational Site 404	Mosonmagyaróvár
Hungary	Teva Investigational Site 403	Sopron
Hungary	Teva Investigational Site 407	Százhalombatta
Hungary	Teva Investigational Site 402	Tatabánya
Israel	Teva Investigational Site 422	Petach Tikva
Israel	Teva Investigational Site 421	Rehovot
Israel	Teva Investigational Site 420	Tel-Aviv
Mexico	Teva Investigational Site 203	Distrito Federal
Mexico	Teva Investigational Site 205	Distrito Federal
Mexico	Teva Investigational Site 204	Guadalajara, JAL
Mexico	Teva Investigational Site 200	Hermosillo, Sonora
Mexico	Teva Investigational Site 202	Tijuana, B.C.
Netherlands	Teva Investigational Site 460	Heerlen
Poland	Teva Investigational Site 507	Bialystok
Poland	Teva Investigational Site 513	Gdansk
Poland	Teva Investigational Site 512	Lodz
Poland	Teva Investigational Site 505	Lublin
Poland	Teva Investigational Site 500	Ostrow Wielkopolski
Poland	Teva Investigational Site 502	Sopot
Poland	Teva Investigational Site 504	Tarnow
Sweden	Teva Investigational Site 602	Göteborg
Sweden	Teva Investigational Site 600	Lund
Sweden	Teva Investigational Site 601	Malmö
United States	Teva Investigational Site 12	Anaheim	California
United States	Teva Investigational Site 21	Charleston	South Carolina
United States	Teva Investigational Site 20	Cincinnati	Ohio
United States	Teva Investigational Site 2	Colorado Springs	Colorado
United States	Teva Investigational Site 16	Fort Worth	Texas
United States	Teva Investigational Site 11	Fountain Valley	California
United States	Teva Investigational Site 10	Houston	Texas
United States	Teva Investigational Site 7	Iowa City	Iowa
United States	Teva Investigational Site 24	Largo	Florida
United States	Teva Investigational Site 6	Lilburn	Georgia
United States	Teva Investigational Site 73	Lincoln	Rhode Island
United States	Teva Investigational Site 43	Los Angeles	California
United States	Teva Investigational Site 1	Medford	Oregon
United States	Teva Investigational Site 27	Miami	Florida
United States	Teva Investigational Site 5	Miami	Florida
United States	Teva Investigational Site 8	Omaha	Nebraska
United States	Teva Investigational Site 4	Orange	California
United States	Teva Investigational Site 9	Providence	Rhode Island
United States	Teva Investigational Site 14	San Antonio	Texas
United States	Teva Investigational Site 45	San Antonio	Texas
United States	Teva Investigational Site 3	Savannah	Georgia
United States	Teva Investigational Site 26	Summit	New Jersey
United States	Teva Investigational Site 19	Tallahassee	Florida
United States	Teva Investigational Site 17	Trinity	Florida
United States	Teva Investigational Site 18	Valrico	Florida
United States	Teva Investigational Site 15	Walnut Creek	California

Sponsors (1)

Lead Sponsor	Collaborator
Cephalon

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Canada,  Colombia,  France,  Hungary,  Israel,  Mexico,  Netherlands,  Poland,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall change from baseline as assessed by Forced Expiratory Volume in 1 second (FEV1)	baseline to week 16 (or early withdrawal)	baseline to week 16	No
Secondary	Lung function as measured by percent predicted Forced Expiratory Volume in 1 second (% predicted FEV1)	from baseline to weeks 4, 8, 12, 16 or early withdrawal	baseline to week 16	No
Secondary	Lung function as measured by Forced Vital Capacity (FVC)	from baseline to weeks 4, 8, 12, 16 or early withdrawal	baseline to week 16	No
Secondary	Lung function as measured by Forced Expiratory Flow at 25% to 75% of FVC (FEF25-75%)	from baseline to weeks 4, 8, 12, 16 or early withdrawal	baseline to week 16	No
Secondary	Short-acting beta-agonist use	from baseline to weeks 4, 8, 12, 16 or early withdrawal	baseline to week 16	No
Secondary	Blood eosinophil count	from baseline to weeks 4, 8, 12, 16 and follow-up or early withdrawal	baseline to week 16	No
Secondary	Asthma symptoms as measured by the Asthma Symptom Utility Index (ASUI)	from baseline to weeks 4, 8, 12, 16 or early withdrawal	baseline to week 16	No
Secondary	Asthma control as measured by the Asthma Control Questionnaire (ACQ)	from baseline to weeks 4, 8, 12, 16 or early withdrawal	baseline to week 16	No
Secondary	Quality of life as measured by the Asthma Quality of Life Questionnaire (AQLQ)	from baseline to week 16 or early withdrawal	baseline to week 16	No
Secondary	Evaluate the safety and tolerability of reslizumab treatment	16 weeks + 90 day follow-up: occurrence of adverse events; clinical laboratory test results; vital signs (blood pressures, pulse, body temperature, and respiratory rate) measurements at weeks 4, 8, 12, and 16 or early withdrawal and 90 (±7) days after the end-of treatment evaluation.; physical examination findings, including body weight measurements, at weeks 4, 8, 12, and 16 or early withdrawal; 12-lead electrocardiography (ECG) findings at week 16 or early withdrawal; concomitant medication usage throughout the study	7 months	Yes