Ignite Creation Date:
2024-05-05 @ 4:36 PM
Last Modification Date:
2024-10-26 @ 9:22 AM
Study NCT ID:
NCT00278083
Status:
COMPLETED
Last Update Posted:
2023-09-14
First Post:
2006-01-17
Brief Title:
TNF-alpha Directed Therapy in Asthma
Sponsor:
Imperial College London
Organization:
Imperial College London
Study Overview
Official Title:
A Randomised Double Blind Placebo-controlled Parallel Group Pilot Study to Determine the Effect of REMICADE on Safety Efficacy and Biomarkers of Inflammation in Patients With Asthma Receiving Inhaled Corticosteroids
Status:
COMPLETED
Status Verified Date:
2023-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This trial is a randomised single-center placebo-controlled double blind parallel group study in patients with asthma symptomatic on inhaled steroids
This trial will examine the efficacy and safety of 5 mgkg doses of infliximab in patients with inhaled corticosteroid-dependent asthma The primary objective of this study is to obtain pharmacological evidence for a role of the pro-inflammatory cytokine TNF-alpha in patients with asthma symptomatic on inhaled steroids and to evaluate the safety and tolerability of repeated intravenous administration of infliximab
This trial will examine the efficacy and safety of 5 mgkg doses of infliximab in patients with inhaled corticosteroid-dependent asthma The primary objective of this study is to obtain pharmacological evidence for a role of the pro-inflammatory cytokine TNF-alpha in patients with asthma symptomatic on inhaled steroids and to evaluate the safety and tolerability of repeated intravenous administration of infliximab
Detailed Description:
Study Overview This trial is a randomised single-center placebo-controlled double blind parallel group study in patients with asthma symptomatic on inhaled steroids
Patient Population Patients eligible for this study will have a diagnosis of moderate asthma defined by the American Thoracic Society criteria for 1 year These patients should be taking inhaled steroids at doses equivalent to 400µg and 2000µg per day beclomethasone diproprionate but not oral steroid medication Patients taking additional oral steroids are required to stop oral medication at least one month prior to pre-screening
Many of these patients will be receiving long-acting beta2-agonists and this therapy will be discontinued for 48h before starting the run-in In addition the following therapies are not allowed 1 anticholinergics 2 theophylline 3 oral beta2-agonists 4 antihistamines 5 inhaled cromolyn sodium or nedocromil 6 leukotriene antagonists
Patients using these prohibited medications will be asked to discontinue use 2 weeks prior to the screening examination During this washout period patients will keep a clinical diary and will remain in contact with the clinical research center
Eligible patients for screening will maintain stable doses of their normal inhaled steroids in doses equivalent to 400 µg and 2000µg per day beclomethasone diproprionate and will be able to use short-acting beta2-agonists for symptom relief
Screening At screening eligible patients will have a baseline screening FEV1 of 60 to 90 of predicted at least 4 hours after the last usage of a short-acting beta2-agonist Patients will have reversible airway obstruction a 12 increase in FEV1 in comparison to baseline should be shown within 30 minutes after taking 200 µg salbutamol If airway reversibility cannot be demonstrated during this visit patients are eligible for re-testing Reversible airway disease may be demonstrated at any time between screening and start of run-in period The 2 to 4 week run-in period will start immediately after demonstration of reversible lung disease
Patients will also have skin tests to a standard battery of bronchial allergens performed at screening Patients should have both a purified protein derivative PPD skin test and a chest radiograph prior to their first infusion Patients with evidence of either latent or active tuberculosis TB will not be enrolled
Run-in Period Following acceptable screening tests patients will complete a baseline run-in of 2 to 4 weeks duration prior to the study start During this period patients will be required to keep a symptom diary and to record baseline lung function parameters using an electronic spirometer As before patients will be maintained on their normal inhaled steroids in doses equivalent to 400 µg and 2000µg per day beclomethasone diproprionate and will be able to use short-acting beta2-agonists for symptom relief No other asthma medications will be allowed during this period and the rest of the study Use of all other non-asthma medication will be reviewed by the Investigator and allowed at hisher discretion provided a stable dose regimen is maintained where possible throughout the study
Baseline Visit day -1 The day before the first drug administration patients will attend the clinical research unit and diary cards will be reviewed In order to enter the study the patients must have a mean total daily symptom score 4 measured during the last 7 days of the baseline run-in period A symptom scale with scores ranging from 0 symptom free to 3 severe symptoms is used with 6 questions and a total maximum daily symptom score of 18 see appendix D andor have a 10 and 30 diurnal variation in PEFR measured on at least 2 of 7 days during the same period
Diurnal variation in PEFR is defined from morning and evening PEFR values in the morning and evening the PEFR is determined on 3 immediately consecutive occasions and the highest value taken The calculation of diurnal variation is based on
higher am or pm PEFR- lower am or pm PEFR higher am or pm PEFR x 100
In eligible patients the following pharmacodynamic assessments will be made breath NO levels non-nasal and breath condensates pulmonary function testing FEV1 FVC and PEFR sputum induction for markers of inflammation and a blood sample collection for the measurement of markers of inflammation
Study Treatments Patients will be randomised in a 11 ratio to treatment with infliximab or placebo respectively PRI will provide the randomisation list At t0 weeks patients will either receive 5 mgkg infliximab Group I n20 or placebo Group II n20 Subsequently infliximab or placebo will be infused at weeks 2 and 6 Throughout the study period up to week 12 patients will be allowed to use inhaled corticosteroids at a stable dose regimen Salbutamol a short-acting beta2-agonist will be allowed as necessary to relieve symptoms
During the study the two treatment groups are defined as
Group I Infliximab 5 mgkg short-acting beta2-agonist as needed inhaled corticosteroids equivalent to 400 µg and 2000µg per day beclomethasone diproprionate
Group II Placebo short-acting beta2-agonist as needed inhaled corticosteroids equivalent to 400 µg and 2000µg per day beclomethasone diproprionate
Study Evaluations Throughout the study starting with the baseline run-in period patients will be required to daily record their PEFR and FEV1 morning and evening short-acting beta2-agonist use and clinical symptoms using a diary card Mean weekly scores will be calculated for each parameter starting at week -1 up to week 12 Prior to administration of study drug at week 0 and in addition at weeks 1 8 and 12 the following pharmacodynamic assessments will be made breath NO levels breath condensate leukotriene B4 C4 pulmonary function testing FEV1 FVC and PEFR sputum induction for markers of inflammation weeks 0 1 and 8 only and levels of markers of inflammation in peripheral blood In addition at weeks 2 and 6 breath NO levels will be measured and pulmonary function testing will be performed
Safety Safety evaluations will include measurement of vital signs during and immediately after for 2 hours the infusion of study medications and assessment of adverse events AEs at each of the evaluation visits Additional vital signs and lung function measurements will be performed immediately after each infusion and at t 1 and 2 hours post dose Routine laboratory tests will be performed at screening at day -1 and at weeks 2 6 8 and 12 During the study the medical monitor will regularly review safety data
Follow-up During the last visit in week 12 to the clinical research center a follow-up examination including a physical examination and blood and urine chemistry will be performed
Patient Population Patients eligible for this study will have a diagnosis of moderate asthma defined by the American Thoracic Society criteria for 1 year These patients should be taking inhaled steroids at doses equivalent to 400µg and 2000µg per day beclomethasone diproprionate but not oral steroid medication Patients taking additional oral steroids are required to stop oral medication at least one month prior to pre-screening
Many of these patients will be receiving long-acting beta2-agonists and this therapy will be discontinued for 48h before starting the run-in In addition the following therapies are not allowed 1 anticholinergics 2 theophylline 3 oral beta2-agonists 4 antihistamines 5 inhaled cromolyn sodium or nedocromil 6 leukotriene antagonists
Patients using these prohibited medications will be asked to discontinue use 2 weeks prior to the screening examination During this washout period patients will keep a clinical diary and will remain in contact with the clinical research center
Eligible patients for screening will maintain stable doses of their normal inhaled steroids in doses equivalent to 400 µg and 2000µg per day beclomethasone diproprionate and will be able to use short-acting beta2-agonists for symptom relief
Screening At screening eligible patients will have a baseline screening FEV1 of 60 to 90 of predicted at least 4 hours after the last usage of a short-acting beta2-agonist Patients will have reversible airway obstruction a 12 increase in FEV1 in comparison to baseline should be shown within 30 minutes after taking 200 µg salbutamol If airway reversibility cannot be demonstrated during this visit patients are eligible for re-testing Reversible airway disease may be demonstrated at any time between screening and start of run-in period The 2 to 4 week run-in period will start immediately after demonstration of reversible lung disease
Patients will also have skin tests to a standard battery of bronchial allergens performed at screening Patients should have both a purified protein derivative PPD skin test and a chest radiograph prior to their first infusion Patients with evidence of either latent or active tuberculosis TB will not be enrolled
Run-in Period Following acceptable screening tests patients will complete a baseline run-in of 2 to 4 weeks duration prior to the study start During this period patients will be required to keep a symptom diary and to record baseline lung function parameters using an electronic spirometer As before patients will be maintained on their normal inhaled steroids in doses equivalent to 400 µg and 2000µg per day beclomethasone diproprionate and will be able to use short-acting beta2-agonists for symptom relief No other asthma medications will be allowed during this period and the rest of the study Use of all other non-asthma medication will be reviewed by the Investigator and allowed at hisher discretion provided a stable dose regimen is maintained where possible throughout the study
Baseline Visit day -1 The day before the first drug administration patients will attend the clinical research unit and diary cards will be reviewed In order to enter the study the patients must have a mean total daily symptom score 4 measured during the last 7 days of the baseline run-in period A symptom scale with scores ranging from 0 symptom free to 3 severe symptoms is used with 6 questions and a total maximum daily symptom score of 18 see appendix D andor have a 10 and 30 diurnal variation in PEFR measured on at least 2 of 7 days during the same period
Diurnal variation in PEFR is defined from morning and evening PEFR values in the morning and evening the PEFR is determined on 3 immediately consecutive occasions and the highest value taken The calculation of diurnal variation is based on
higher am or pm PEFR- lower am or pm PEFR higher am or pm PEFR x 100
In eligible patients the following pharmacodynamic assessments will be made breath NO levels non-nasal and breath condensates pulmonary function testing FEV1 FVC and PEFR sputum induction for markers of inflammation and a blood sample collection for the measurement of markers of inflammation
Study Treatments Patients will be randomised in a 11 ratio to treatment with infliximab or placebo respectively PRI will provide the randomisation list At t0 weeks patients will either receive 5 mgkg infliximab Group I n20 or placebo Group II n20 Subsequently infliximab or placebo will be infused at weeks 2 and 6 Throughout the study period up to week 12 patients will be allowed to use inhaled corticosteroids at a stable dose regimen Salbutamol a short-acting beta2-agonist will be allowed as necessary to relieve symptoms
During the study the two treatment groups are defined as
Group I Infliximab 5 mgkg short-acting beta2-agonist as needed inhaled corticosteroids equivalent to 400 µg and 2000µg per day beclomethasone diproprionate
Group II Placebo short-acting beta2-agonist as needed inhaled corticosteroids equivalent to 400 µg and 2000µg per day beclomethasone diproprionate
Study Evaluations Throughout the study starting with the baseline run-in period patients will be required to daily record their PEFR and FEV1 morning and evening short-acting beta2-agonist use and clinical symptoms using a diary card Mean weekly scores will be calculated for each parameter starting at week -1 up to week 12 Prior to administration of study drug at week 0 and in addition at weeks 1 8 and 12 the following pharmacodynamic assessments will be made breath NO levels breath condensate leukotriene B4 C4 pulmonary function testing FEV1 FVC and PEFR sputum induction for markers of inflammation weeks 0 1 and 8 only and levels of markers of inflammation in peripheral blood In addition at weeks 2 and 6 breath NO levels will be measured and pulmonary function testing will be performed
Safety Safety evaluations will include measurement of vital signs during and immediately after for 2 hours the infusion of study medications and assessment of adverse events AEs at each of the evaluation visits Additional vital signs and lung function measurements will be performed immediately after each infusion and at t 1 and 2 hours post dose Routine laboratory tests will be performed at screening at day -1 and at weeks 2 6 8 and 12 During the study the medical monitor will regularly review safety data
Follow-up During the last visit in week 12 to the clinical research center a follow-up examination including a physical examination and blood and urine chemistry will be performed
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None