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

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

Detailed Description
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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.

Official Title
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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

Conditions
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Asthma

Intervention / Treatment
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* Drug: CNTO148
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CNTO 148 (golimumab)<br> | Drug: CNTO148<br>* Type=exact type, unit=mg, number=50, 75, 100, 150, 200 and 300, form=injection, route=subcutaneous. Every 4 weeks partciapnts will receive injections in 4 parallel treatment arms<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Type=exact type, unit=mg, form=injection, route=subcutaneous. Placebo will be given from from Week 0 through Week 52.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Prebronchodilator Clinic-Measured, Percent-Predicted Forced Expiratory Volume in 1 Second | 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. | Baseline and Week 24 | 
| Number of Severe Asthma Exacerbations Per Patient From Baseline Through 6 Months | The endpoint is the average number of severe asthma exacerbations per patient from baseline through 6 months. | Baseline to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Asthma Quality of Life Questionnaire Score at 6 Months; Randomized Patients | 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). | Baseline to Week 24 | 
| Change From Baseline in Rescue Medication Use at 6 Months; Randomized Patients | 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. | Baseline to Week 24 | 
| 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 | 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 | Week 24 to Week 52 | 
| Change From Baseline in Oral Corticosteroids Dose at Week 52; Randomized Patients Who Received Oral Corticosteroids at Baseline | 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. | Baseline and Week 52 | 
| Change From Baseline in Domiciliary Morning Peak Expiratory Flow Rate (PEFR) at 6 Months; Randomized Subjects | 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. | Baseline to Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Severe Persistent Asthma, Subcutaneous injections, Immunology disorder, Breathlesness