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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Change from baseline (prior to visit 4: days -7 to -1) to week 8 (prior to visit 8: days 49-56) in mean morning PEFR from clinical diaries:
研究概览
简要总结
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 mg/kg 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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have a diagnosis of moderate asthma as defined by the American Thoracic Society criteria (NIH, 1997) for > 1 year.
- •Men and women, >/= 18 to </= 60 years of age and within 60-140% of desirable height and weight range established by the 1983 Metropolitan Life Insurance Company standards.
- •Non-smoker for at least 1 year and less than a 10 pack year history of smoking.
- •Screening values for haematology, biochemistry and urinalysis should be within clinically acceptable limits for this patient group.
- •Chest radiograph at screening must show no evidence of malignancy, infection, or fibrosis. The chest radiographs should also show no apical scarring, cavitary lesions, or calcified granulomas, as evidence of past tuberculosis infections.
- •Serological assays for hepatitis B and C must be negative for active infection.
排除标准
- •Are pregnant, nursing, or planning a pregnancy within 12 months of enrolment.
- •Diagnosis of chronic obstructive pulmonary disease, cystic fibrosis or other significant respiratory disorder (excluding asthma).
- •Exacerbation of asthma symptoms requiring hospitalisation within the previous 12 weeks.
- •History of clinically significant seasonal allergies will require that the patient is studied outside the allergy season.
- •Have been previously treated with infliximab or any other therapeutic agent targeted at reducing TNF.
- •Have been treated with any anti-CD-4 antibody.
- •Have been treated with any investigational drug within the previous 3 months or within 5 half-lives, whichever is greater.
- •Have previously used cyclophosphamide, nitrogen mustard, chlorambucil, or other alkylating agents.
- •Have a history of any clinically significant adverse reaction to murine or chimeric proteins, including but not limited to allergic reactions.
- •Have had a serious infection during the previous 2 months.
- •Have a chronic or recurrent infectious disease
- •Have a history of opportunistic infections
- •Have current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease.
- •Have a history of lymphoproliferative disease, including lymphoma
- •Currently have any known malignancy or have a history of malignancy within the previous 5 years.
- •Have had substance abuse (drug or alcohol) problem within the previous 10 years.
- •Use of restricted respiratory medication prior to screening within the following time periods: 1) oral or systemic steroids, 1 month; 2) immunosuppressant therapy, 3 months.
- •Have a history of chronic cough, haemoptysis, weight loss, or pyrexia considered suggestive of possible current tuberculosis infection.
- •Patients with current active tuberculosis (TB) or atypical mycobacterial infection or a previous history of these infections.
- •Be considered at high risk for tuberculosis according to US Centers for Disease Control and Prevention (CDC) criteria,
- •A tuberculin (purified protein derivative, PPD) intradermal skin test > 10mm induration.
- •Have demyelinating disease (multiple sclerosis), autoimmune conditions such as systemic lupus.
结局指标
主要结局
Change from baseline (prior to visit 4: days -7 to -1) to week 8 (prior to visit 8: days 49-56) in mean morning PEFR from clinical diaries:
The morning PEFR for a 7 day period (week 7 to 8) will be compared to the 7 day period prior to first administration (days -7 to -1).
次要结局
- 9. Sputum levels of IL-8, TNF-alpha and eotaxin (in supernatant) and differential white cell count
- 1. Evening PEFR
- 2. FEV1 from clinical diaries and on study visits
- 3. Diurnal variation in PEFR
- 4. Symptoms score
- 5. Short-acting beta2-agonist usage = rescue salbutamol
- 6. Exacerbation's and episode-free days
- 7. Quality of life (St. George's Respiratory Questionnaire)
- 8. Exhaled breath NO and breath condensates
- 11. Expression of mRNA related to inflammation in peripheral blood
- 10. Peripheral blood eosinophil count, and total IgE