A Study of Safety and Efficacy of CNTO 148 in Patients With Severe Persistent Asthma

Phase 2

Completed

• Conditions: Asthma
• Interventions: Drug: CNTO148; Drug: Placebo

• Registration Number: NCT00207740
• Lead Sponsor: Centocor, Inc.

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.

Study Timeline

• Study Start: 2004-08
• Study First Submitted: 2005-09-13
• Study First Submitted QC: 2005-09-13
• Study First Posted: 2005-09-21
• Primary Completion: 2007-07
• Study Completion: 2007-07
• Results First Submitted: 2009-05-21
• Results First Submitted QC: 2012-05-01
• Results First Posted: 2012-06-01
• Status Verified: 2012-08
• Last Update Submitted: 2012-08-14
• Last Update Posted: 2012-08-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 309

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CNTO 148 (golimumab)	CNTO148	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Prebronchodilator Clinic-Measured, Percent-Predicted Forced Expiratory Volume in 1 Second	Baseline and Week 24	The endpoint is change from baseline in prebronchodilator clinic-measured percent predicted Percent-Predicted Forced Expiratory Volume in 1 Second (FEV1) with Last Observation Carried Forward (LOCF) at 6 months. The baseline visit starts at the end of 2 weeks run in phase.
Number of Severe Asthma Exacerbations Per Patient From Baseline Through 6 Months	Baseline to Week 24	The endpoint is the average number of severe asthma exacerbations per patient from baseline through 6 months.

Secondary Outcome Measures

Name	Time	Method
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	Week 24 to Week 52	The endpoint is the average number of severe asthma exacerbations per patient from Week (Wk) 24 through Wk 52 for the patients who did not discontinue study participation prior to Wk 24
Change From Baseline in Asthma Quality of Life Questionnaire Score at 6 Months; Randomized Patients	Baseline to Week 24	The endpoint is the change from baseline in the overall Asthma Quality of Life Questionnaire (AQLQ) score at 6 months. The AQLQ is a validated and self-administered questionnaire to evaluate symptoms and Quality of Life (QOL) in subjects with asthma and it has 32 questions in 4 domains (symptoms, activity limitations, emotional function, and environmental stimuli). Participants were asked to score the importance of each of the positively identified problems on a 7-point scale (7 = not impaired at all - 1 = severely impaired).
Change From Baseline in Rescue Medication Use at 6 Months; Randomized Patients	Baseline to Week 24	The endpoint is change from baseline in rescue medication use at Wk 24 where the rescue medication use was based on the average over 7 days prior to visit.
Change From Baseline in Oral Corticosteroids Dose at Week 52; Randomized Patients Who Received Oral Corticosteroids at Baseline	Baseline and Week 52	The endpoint is the change from baseline at Week (Wk) 52 in oral corticosteroids (OCS) dose for the randomized patients who received OCS at baseline.
Change From Baseline in Domiciliary Morning Peak Expiratory Flow Rate (PEFR) at 6 Months; Randomized Subjects	Baseline to Week 24	The endpoint is the change from baseline in domiciliary morning PEFR at Week 24. PEFR- Peak Expiratory Flow Rate (PEFR): A measure of the speed of exhalation. The data were collected in the eDiary which was issued to each participant at screening. PEFR was collected morning and evening each day of the study.