Asthma is a chronic inflammatory bronchial disorder with three distinct components: airway hyper-responsiveness (respiratory hypersensitivity), airway inflammation, and intermittent airway obstruction. One of the characteristics of the disease is an inflammatory reaction of the immune system caused by cytokine production. A substantial number of asthma patients do not satisfactorily respond to steroid therapy and consequently have an unmet medical need for novel targeted therapies with improved specificity, tolerability, and compliance. Novel therapeutic strategies for the treatment of chronic inflammatory diseases by targeting early disease-causing mechanisms are a promising approach for the treatment of asthma. The transcription factor GATA-3 plays a key role in mediating the asthmatic immune response and has been shown to be necessary and sufficient for the production of cytokines interleukin (IL)-4, IL-5, and IL-13. The active drug substance of the investigational medicinal product SB010 is hgd40. SB010 belongs to a new class of antisense oligonucleotide therapeutics, the 10-23 DNA (deoxyribonucleic acid)zymes (antisense oligonucleotide). DNAzymes are catalytically active nucleic acids that cleave complementary RNA (ribonucleic acid) molecules. By cleaving GATA-3 mRNA, hgd40 reduces specific cytokine production and thereby reduces key features of allergic airway inflammation. DNAzymes are generated completely by chemical synthesis and can be produced under Good Manufacturing Practice (GMP) controlled conditions. The DNAzymes are not biological drugs, i.e. they are not generated by use of any living organism including cell culture or bacteria. The molecules are highly water-soluble and will be applied as solution directly in their synthesized form. This proof-of-concept study will evaluate the safety, tolerability, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of multiple doses of inhaled SB010 in male patients with mild asthma.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
38
Charité Research Organisation GmbH
Berlin, Germany
Clinical Research Centre RespiratoryMedicine (IKF)
Frankfurt, Germany
Inamed GmbH
Gauting, Germany
Pulmonary Research Institute (PRI)
Großhansdorf, Germany
Clinical Airway Research Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM)
Hanover, Germany
Johannes Gutenberg University Medical Clinic III for Hematology, Oncology and Pneumology
Mainz, Germany
insaf - Respiratory Research Institute GmbH
Wiesbaden, Germany
Change in late phase response after allergen challenge (AC), following multiple doses of inhaled SB010
After 28 days of treatment with SB010 or placebo, patients will undergo allergen bronchoprovocation \[allergen challenge (AC)\]. The results from AC on Day 28 will be compared to results obtained on Enrolment (Day -1). Allergen for AC will be selected based on skin prick test performed at Screening. The dose of selected allergen will be determined based on skin prick dilution test. After the AC, serial spirometry will be used to assess the influence of inhaled SB010 on the area under the Forced Expiratory Volume in 1 second (FEV1) curve during the late asthma response (LAR, 4 - 7 hours); measurement time points will be at 4, 5, 6, and 7 hours after AC. The spirometric parameters FEV1 and forced vital capacity (FVC), obtained during pulmonary function testing, will be used to derive the primary efficacy variable AUC4-7 FEV1.
Time frame: Day -1 and Day 28 (monitoring for 7 h after AC).
Number of patients with adverse events after multiple doses of inhaled SB010
Investigate occurrence of adverse events.
Time frame: Screening examination (Day -56 to -14 before first drug administration); Study period (Day 1 to 28); Follow-up visit (Day 88±4); Maximum of 149 days for a particular subject.
Number of patients with changes in vital signs after multiple doses of inhaled SB010
Investigate any change in vital signs.
Time frame: Screening examination (Day -56 to -14 before first drug administration); Study period (Day 1 to 28); Follow-up visit (Day 88±4); Maximum of 149 days for a particular subject.
Number of patients with changes in electrocardiogram (ECG) after multiple doses of inhaled SB010
Investigate any change in electrocardiogram (ECG).
Time frame: Screening examination (Day -56 to -14 before first drug administration); Study period (Day 1 to 28); Follow-up visit (Day 88±4); Maximum of 149 days for a particular subject.
Number of patients with changes in safety laboratory tests after multiple doses of inhaled SB010
Investigate any change in safety laboratory tests (clinical chemistry, coagulation, immune monitoring, hematology, urine analysis).
Time frame: Screening examination (Day -56 to -14 before first drug administration); Study period (Day 1 to 28); Follow-up visit (Day 88±4); Maximum of 149 days for a particular subject.
Number of patients with changes in spirometry laboratory tests (FEV1, FVC) after multiple doses of inhaled SB010
Investigate the number of patients with changes in spirometry laboratory tests \[Forced expiratory volume in 1 second (FEV1), Forced vital capacity (FVC)\], after multiple doses of inhaled SB010.
Time frame: Screening examination (Day -56 to -14 before first drug administration); Study period (Day 1 to 28); Follow-up visit (Day 88±4); Maximum of 149 days for a particular subject.
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