Clinical trial NCT00207740: A Study of Safety and Efficacy of CNTO 148 in Patients With Severe Persistent Asthma
Official title: A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Dose-ranging Study Evaluating the Efficacy and Safety of CNTO 148 Administered Subcutaneously in Symptomatic Subjects With Severe Persistent Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Keywords: Asthma
Severe Persistent Asthma
Subcutaneous injections
Immunology disorder
Breathlesness
Lead sponsor: Centocor, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Centocor BV
First posted: 2005-09-21
Enrollment: 309
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the effectiveness and safety of CNTO 148 (golimumab) in patients with severe persistent asthma.

Detailed description: This is a multicenter, randomized (the study medication is assigned by chance), double-blind (neither physician nor patient knows the treatment that the patient receives), placebo-controlled (an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical study), parallel-group (each group of patients will be treated at the same time), dose-ranging study to evaluate the efficacy and safety of CNTO 148. The study will consists of run-in phase (2 weeks), treatment period (52 weeks) and follow up period (24 weeks). The patients inhaled corticosteroids (ICS) medication will be standardized in the run-in phase and the treatment period contains first 24 weeks of treatment, the patients are required to remain on stable doses of concomitant corticosteroids (CS) medication (steroid stable phase). The steroid stable phase is followed by a 28-week steroid taper phase, during which a reduction of concomitant CS medication will be attempted. After completion of the study treatment, patients are to be followed for an additional 24 weeks. Patients will receive subcutaneous injections of 75, 150, or 300 mg of CNTO 148 or placebo every 4 weeks for 52 weeks followed 50,100, or 200 mg every 4 weeks through week 52. The safety of the patient will be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

* Physician diagnosis of asthma for greater than or equal to 3 years and a diagnosis of severe persistent asthma forgreater than or equal to 1 year prior to screening
* Continuous treatment with high dose Inhaled corticosteroids (ICS) and long acting beta-agonist for at least 3 months prior to screening
* Have evidence of at least 1 of the following in the 5 years prior to screening or during screening, reversible airway obstruction greater than or equal to 12 percentage change in forced expiratory volume in 1 second (FEV1) postbronchodilator; Diurnal variation in peak expiratory flow rate (PEFR) greater than or equal to 30 percentage change) and airway hyperresponsiveness
* Estimated frequency of symptoms on more than one-third of days for at least 3 months prior to screening (eg, wheezing, breathlessness, chest tightness, cough, nocturnal awakening) despite treatment with high dose ICS and long-acting β2-agonist (LABA), with or without continuous oral corticosteroids
* Score of greater than or equal to 2 points on the asthma control questionnaire at screening.

Exclusion Criteria:

* Diagnosis of chronic obstructive pulmoanry disease (COPD), cystic fibrosis, or other significant respiratory disorder
* Worsening of asthma symptoms that required treatment with an addition or increase in oral corticosteroids dose (steroid burst) in the 4-week period prior to the screening visit
* Life-threatening asthma attack requiring cardiopulmonary support (eg, intubation) in the 6-month period prior to screening
* Have ever used alkylating agents (eg, chlorambucil or cyclophosphamide)
* Concomitant diagnosis or any history of congestive heart failure (CHF), including medically controlled CHF.

Primary outcomes:
measure: Change From Baseline in Prebronchodilator Clinic-Measured, Percent-Predicted Forced Expiratory Volume in 1 Second
timeFrame: Baseline and Week 24
measure: Number of Severe Asthma Exacerbations Per Patient From Baseline Through 6 Months
timeFrame: Baseline to Week 24
Secondary outcomes:
measure: Change From Baseline in Asthma Quality of Life Questionnaire Score at 6 Months; Randomized Patients
timeFrame: Baseline to Week 24
measure: Change From Baseline in Rescue Medication Use at 6 Months; Randomized Patients
timeFrame: Baseline to Week 24
measure: Number of Severe Asthma Exacerbations Per Patient From Week 24 Through Week 52; Randomized Patients Who Did Not Discontinue Study Participation Prior to Week 24
timeFrame: Week 24 to Week 52
measure: Change From Baseline in Oral Corticosteroids Dose at Week 52; Randomized Patients Who Received Oral Corticosteroids at Baseline
timeFrame: Baseline and Week 52
measure: Change From Baseline in Domiciliary Morning Peak Expiratory Flow Rate (PEFR) at 6 Months; Randomized Subjects
timeFrame: Baseline to Week 24
Other outcomes:
Locations:
city: Los Angeles
country: United States
state: California
city: San Diego
country: United States
state: California
city: Stockton
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Hartford
country: United States
state: Connecticut
city: New Haven
country: United States
state: Connecticut
city: Chicago
country: United States
state: Illinois
city: Normal
country: United States
state: Illinois
city: River Forest
country: United States
state: Illinois
city: Iowa City
country: United States
state: Iowa
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: North Dartmouth
country: United States
state: Massachusetts
city: Minneapolis
country: United States
state: Minnesota
city: Saint Louis
country: United States
state: Missouri
city: St. Louis
country: United States
state: Missouri
city: Cortland
country: United States
state: New York
city: Elmira
country: United States
state: New York
city: Charlotte
country: United States
state: North Carolina
city: Winston-Salem
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Lake Oswego
country: United States
state: Oregon
city: Medford
country: United States
state: Oregon
city: Portland
country: United States
state: Oregon
city: Philadelphia
country: United States
state: Pennsylvania
city: El Paso
country: United States
state: Texas
city: Richmond
country: United States
state: Virginia
city: Bellingham
country: United States
state: Washington
city: Madison
country: United States
state: Wisconsin
city: Gent
country: Belgium
city: Russel
country: Bulgaria
city: Sofia
country: Bulgaria
city: Ostrava
country: Czech Republic
city: Poruba
country: Czech Republic
city: Usti Nad Labem
country: Czech Republic
city: Montpellier Cedex 9
country: France
city: Pessac
country: France
city: Tarbes
country: France
city: Berlin
country: Germany
city: Großhansdorf
country: Germany
city: Leipzig
country: Germany
city: Mainz
country: Germany
city: Budapest
country: Hungary
city: Nyiregyhaza
country: Hungary
city: Szekesfehervar
country: Hungary
city: Szombathely
country: Hungary
city: Törökbálint
country: Hungary
city: Leiden
country: Netherlands
city: Bienkowka
country: Poland
city: Katowice
country: Poland
city: Lodz
country: Poland
city: Torun
country: Poland
city: Warszawa
country: Poland
city: Linkoeping
country: Sweden
city: Stockholm
country: Sweden
city: Glasgow
country: United Kingdom
city: Southampton
country: United Kingdom
Study officials:
affiliation: Centocor, Inc.
name: Centocor, Inc. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Wenzel SE, Barnes PJ, Bleecker ER, Bousquet J, Busse W, Dahlen SE, Holgate ST, Meyers DA, Rabe KF, Antczak A, Baker J, Horvath I, Mark Z, Bernstein D, Kerwin E, Schlenker-Herceg R, Lo KH, Watt R, Barnathan ES, Chanez P; T03 Asthma Investigators. A randomized, double-blind, placebo-controlled study of tumor necrosis factor-alpha blockade in severe persistent asthma. Am J Respir Crit Care Med. 2009 Apr 1;179(7):549-58. doi: 10.1164/rccm.200809-1512OC. Epub 2009 Jan 8.