An exploratory, randomized, double-blind, placebo controlled study to assess the efficacy of multiple doses of omalizumab (Xolair) in cystic fibrosis complicated by allergic bronchopulmonary aspergillosis - ND

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2007-006648-23-IT
• Date of registration: 22/05/2009
• Prospective Registration: Yes
• Primary sponsor: NOVARTIS FARMA
• Public title: An exploratory, randomized, double-blind, placebo controlled study to assess the efficacy of multiple doses of omalizumab (Xolair) in cystic fibrosis complicated by allergic bronchopulmonary aspergillosis - ND
• Scientific title: An exploratory, randomized, double-blind, placebo controlled study to assess the efficacy of multiple doses of omalizumab (Xolair) in cystic fibrosis complicated by allergic bronchopulmonary aspergillosis - ND
• Date of first enrolment: 06/08/2009
• Target sample size: 60
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-006648-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: Lo studio prevede un periodo di trattamento in cieco e un periodo di 6 mesi di trattamento in aperto If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Belgium, Germany, Ireland, Italy, Netherlands, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
-Males/females age&#8805;12 years -Cystic Fibrosis diagnosed by either gene profiling and/or sweat test -ABPA previously diagnosed according to the Cystic Fibrosis Foundation Consensus Conference recommendations ? minimal diagnostic criteria for diagnosis of ABPA in cystic fibrosis defined as:i)Acute or sub-acute clinical deterioration(cough,wheeze,exercise intolerance,exercise-induced asthma,change in pulmonary function,or increased sputum production)not attributable to another etiology. ii)Total serum IgE concentration of >500IU/mL(1200 ng/mL).iii)Immediate cutaneous reactivity to Aspergillus(prick skin test wheal>3mm in diameter with surrounding erythema,while the patient is not being treated with systemic antihistamines)or in vitro demonstration of IgE antibody to A.fumigatus.iv)One of the following: a)precipitans to A.fumigatus or in vitro demonstration of IgG antibody to A.fumigatus or b)new or recent abnormalities on chest radiography(infiltrates or mucus plugging)or chest CT(bronchiectasis)that has not cleared with antibiotics and standard physiotherapy.-Total serum IgE level of>500IU/ml(will be measured locally at Screening Visit).Screening IgE levels will determine the dose throughout the study.-Patients who are being treated for ABPA by any oral corticosteroid(for at least 8 weeks prior to the first dose of study treatment ?with an OCS entry dose of minimum 5mg/maximum 40mg per day in prednisolone equivalence).Patients must have a history of at least one unsuccessful attempt to taper steroids defined as in the clinician?s judgment,an ABPA exacerbation during taper(chronic ABPA group)or Patients who present with an acute episode of ABPA,either as a first presentation or as a recurrence,and who were taking a maximum dose of prednisolone of 20mg/day(or equivalent)prior to the ABPA flare(acute ABPA group)-Patients must have an FEV1,as measured at the Baseline Visit, of no lower than 90% of their previous best FEV1 as measured at Screening Visit.-FEV1>40% of predicted in patients aged<16years old,and FEV1 of >30% of predicted is acceptable in patients aged &#8805;16 years old as measured after 12 hour washout of LABA\6 hours of SABA. -Female subjects of childbearing potential must be advised that systemic corticosteroids pose a known risk to mother and fetus. Xolair is FDA pregnancy category B. This medication is not expected to be harmful to an unborn.However,patients are advised to use adequate methods of contraception,from the time of screening and for the duration of the study,through study completion. Periodic abstinence(e.g., calendar, ovulation, symptothermal, post-ovulation methods)and withdrawal are not adequate methods of contraception. -Female subjects who report surgical sterilization must have had the procedure at least six (6)months prior to initial dosing.Surgical sterilization procedures should be supported with clinical documentation made available to the sponsor and noted in the Relevant Medical History/Current Medical Conditions section of the CRF.-Postmenopausal females must have had no regular menstrual bleeding for at least one(1)year prior to initial dosing.Menopause will be confirmed by a plasma FSH level of>40IU/L at screening. -Prior to administration of any study procedures,eligible patients(and parents for patients below age 16)must provide written informed consent. -Subjects must be able to communicate well with the investigator;understand and comply with the requirements of th
Exclusion criteria:
-History of cancer in the past 10 years (except surgically-cured basal cell or squamous cell skin cancer). -Any previous history of anaphylaxis. -Any other medical condition that in the opinion of the investigator may cause the patient to be unsuitable for completion of the study or place the patient at potential risk from being in the study. -Pregnant and lactating women. -Prior Xolair exposure. -Lung or other transplant. -Participation in any clinical trial within four (4) weeks prior to initial dosing or longer if required by local regulations, and for any other limitation of participation based on local regulations. -Hemoglobin levels below 10.0 g/dl at screening. -History of immunodeficiency diseases. -Significant illness other than CF/ABPA within two (2) weeks prior to initial dosing. -A past medical history of clinically significant ECG abnormalities.12. Patients who are known to be positive for chronic atypical Mycobacteria and Burkholderia cepacia including subspecies.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients with cystic fibrosis complicated by allergic bronchopulmonary aspergillosis
MedDRA version: 9.1 Level: LLT Classification code 10011763 Term: Cystic fibrosis lung

Intervention(s)

Trade Name: XOLAIR
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: Omalizumab
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-
Pharmaceutical form of the placebo: Powder and solvent for solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Primary end point(s): To assess the efficacy ogf Xolair in adolescent and audult patients with cystic fibrosis (CF) complicated by acute or chronic allergic bronchopulmonary aspergillosis (ABPA) -as measured by the proportion of patient requiring rescue with corticosteroids following 6 months of study treatment -as measured by time to deviation from the protocol pescribed steroid tapering regime

Secondary Objective: -To assess the ABPA exacerbation rates during treatment periods -To assess the changes in FEV1 from baseline, measured after 3 and 6 months of study treatment,and in particular the changes between FEV1 measured pre and post first dose in both the blinded and open label treatment periods -To assess the proportion of patients responding to Xolair treatment,where a responder is defined by a reduction in systemic corticosteroid dose of 50% or more compared to baseline -To measure the time to steroid free state -To assess the change from baseline over time in the average dose of rescue corticosteroid -To assess the proportion of patients in each treatment group(Xolair/placebo)whose steroid dose has reduced to 5mg following 6 months of treatment -To measure the number of steps needed to reduce the steroid dose to zero(or to 5mg or less)following 6 months of treatment -To measure Immunogenicity(anti-omalizumab antibodies) -To measure PK/PD:Total omalizumab levels,Free & Total IgE

Main Objective: To assess the efficacy of Xolair in adolescent and adult patients with cystic fibrosis (CF) complicated by chronic or acute allergic bronchopulmonary aspergillosis (ABPA); as measured by the proportion of patients requiring rescue with corticosteroids following 6 months of study treatment as measured by time to deviation from the protocol prescribed steroid tapering regime

Secondary ID(s)

2007-006648-23-DE

CIGE025A2437