subjects with severe, poorly controlled asthma MedDRA version: 19.0 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Product Name: Sirukumab
Product Code: GSK2973327
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: SIRUKUMAB
CAS Number: N/A
Current Sponsor code: GSK2973327
Other
Sponsors
GlaxoSmithKline, S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A subject will be eligible for inclusion in this study only if all of the following criteria apply: 1. 18 – 75 years, inclusive. 2. Severe, uncontrolled asthma according to the following criteria: a. Physician-diagnosed asthma for = 12 months, and b. Treatment for at least 3 months with =880 micro-g per day of fluticasone propionate (FP) dry powder for inhalation (DPI) or its equivalent, plus a LABA, and c. ACQ-7 score =1.5, and d. A documented history (e.g., medical record verification) in the 12 months prior to Visit 2 of = 1 exacerbation resulting in prescription for systemic oral corticosteroids or hospitalisation or extended observation in a hospital emergency room or outpatient centre. [For subjects on maintenance systemic corticosteroids, at least double the existing maintenance dose for at least 3 days is required] and e. Pre-bronchodilator FEV1 35-80% inclusive, with evidence of =12% (and 200mL) reversibility in FEV1 measured 15-30 minutes following 4 actuations of salbutamol (100 micro-g/actuation) or albuterol (90 micro-g/actuation) via pMDI. This reversibility criterion should have been documented in the 12-months prior to Screening. If no prior data are available this should be demonstrated either at Screening (Visit 2) or at the Randomization visit (Visit 3) f. Blood eosinophil count 40 MlU/ml and estradiol < 40 pg/ml (<140 pmol/L) is confirmatory] or if of child-bearing potential is using a highly effective method for avoidance of pregnancy (refer to Appendix 5) for the duration of dosing and until 4 months post last-dose. 5. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.
Exclusion criteria
Exclusion criteria: 1. Presence of a known pre-existing, clinically important lung condition other than asthma. This includes chronic obstructive pulmonary disease, bronchiectasis, pulmonary fibrosis, bronchopulmonary aspergillosis, or a history of lung cancer. 2. Lower respiratory tract infection or asthma exacerbation requiring antibiotics or systemic corticosteroids within 6 weeks of screening 3. Evidence of respiratory infection at screening 4. Has a history of chronic or recurrent infectious disease or ongoing infection including, but not limited to, chronic renal infection, chronic chest infection, recurrent urinary tract infection, or open, draining skin wound or an ulcer 5. Serious infection within 8 weeks of enrolment, including, but not limited to hepatitis, pneumonia, sepsis, or pyelonephritis; or has been hospitalized for an infection; or has been treated with IV antibiotics for an infection, within 8 weeks prior to the first administration of study drug 6. Opportunistic infection, e.g., a nontuberculous mycobacterial infection or cytomegalovirus, pneumocystosis, aspergillosis within 6 months prior to screening 7. Evidence of poorly controlled chronic medical conditions other than asthma, e.g., patients with known, pre-existing, clinically significant endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, and haematological or any other system abnormalities that are uncontrolled with standard treatment. 8. Current history of suicidal ideation or a past history of suicide attempt. 9. Lactating, pregnant, or planning to become pregnant during the study. 10. Malignancy within 5 years 11. Has a history of known demyelinating diseases such as multiple sclerosis or optic neuritis 12. Has a history of gastrointestinal perforation or currently has active diverticulitis 13. QTc> 450 msec or QTc >480 msec in subjects with Bundle Branch Block 14. ALT >1.5xULN and bilirubin >ULN 15. Laboratory abnormalities: -Neutrophils <1.95 x 109/L -Platelet count <140 × 109/L. -Hemoglobin <8.5g/dL. -WBC count <3.5 × 109/L. 16. Use of systemic corticosteroids within 6 weeks of screening. The only exception is patients who take =10 mg prednisolone orally per day for chronic maintenance therapy, and who have been maintained on this regimen for =12 weeks. 17. The subject has received an investigational drug within 30 days or 5-half-lives prior to the first dose of study drug 18. Use of other monoclonal antibodies within 3 months of screening. 19. Live virus or bacterial vaccine from 30 days before screening. 20. Immunomodulatory/suppressive agents including but not limited to cyclophosphamide, a cytotoxic agent, cyclosporine A, azathioprine, tacrolimus, mycophenolate mofetil, oral or parenteral gold, or D-penicillamine within 3 months of screening. 21. Bronchial thermoplasty within 12 months of screening 22. =10 pack years smoking history (pack years = number of cigarettes smoked per day / 20 * number of years smoked). Note: Patients who are current smokers, or ex-smokers (having given up smoking for =6 months), are eligible for the study if their smoking history is <10 pack years. 23. History of alcohol or illegal substance abuse consumption within 2 years of the study start. 24. History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation. Has any condition that, in
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of sirukumab compared to placebo in patients with severe, uncontrolled asthma.;Secondary Objective: -To evaluate the safety of sirukumab compared to placebo in patients with severe uncontrolled asthma. -To evaluate the efficacy of sirukumab compared to placebo in patients with severe uncontrolled asthma. -To evaluate the population PK of subcutaneously administered sirukumab in patients with severe, uncontrolled asthma. -To evaluate the effects of sirukumab compared to placebo on systemic PD biomarkers of inflammation in patients with severe, uncontrolled asthma. -To evaluate immunogenicity of subcutaneously administered sirukumab in patients with severe, uncontrolled asthma.;Primary end point(s): Change from baseline in Asthma Control Questionnaire (ACQ)-7 at week 24.;Timepoint(s) of evaluation of this end point: Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Incidence of adverse events (AEs) and serious adverse events (SAEs), changes in vital signs; electrocardiograms (ECGs), clinical laboratory parameters. -Change from baseline in ACQ-7 during the treatment period. -Change from baseline in ACQ-5 during the treatment period. -Proportion of patients who achieve an ACQ-7 response. -Change from baseline in pre-bronchodilator FEV1 during the treatment period. -Change from baseline in average a.m. peak expiratory flow rate (PEFR) -Change from baseline in St. George’s Respiratory Questionnaire (SGRQ) -Proportion of patients who achieve a SGRQ response. -Change from baseline in daily salbutamol/albuterol use. -Annualized rate of clinically significant exacerbations during the treatment period. -Serum concentrations of sirukumab and derived population pharmacokinetic (PK parameters). -Change from baseline in blood or serum PD biomarkers including but not limited to IL-6 and C-reactive protein (CRP). -Incidence and titres of serum anti-sirukumab antibodies post-dosing;Timepoint(s) of evaluation of this end point: Endpoints will be assessed at various times during the study: •At Week 24 •At the end of the treatment period (Week 48) •After the drug wash-out period (Week 60) | — |
Countries
France, Germany, Poland, Spain, United States
Contacts
Public ContactCentro de Información
GlaxoSmithKline
Outcome results
None listed