A study to test how well a new medicine called sirukumab works in patients with Severe Uncontrolled Asthma

Phase 1

• Conditions: subjects with severe, poorly controlled asthma; MedDRA version: 19.0Level: PTClassification code 10003553Term: AsthmaSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

• Registration Number: EUCTR2016-001244-19-ES
• Lead Sponsor: GlaxoSmithKline, S.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-07-15
• Last Update Posted: 28 August 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 175

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 <300 cells/micro-L at screening
3. Body mass index 18-45 kg/m2
4. Male or Female
Male subjects with female partners of child bearing potential must comply with the following contraception requirements from the time of first dose of study medication until a cycle of spermatogenesis following five terminal half- lives after the last dose of study medication.
a. Vasectomy with documentation of azoospermia.
b. Male condom plus partner use of one of the contraceptive options below:
-Contraceptive subdermal implant
-Intrauterine device or intrauterine system
-Combined estrogen and progestogen oral contraceptive
-Injectable progesterone
-Contraceptive vaginal ring
-Percutaneous contraceptive patches
This is an all-inclusive list of those methods that meet the following GSK definition of highly effective: having a failure rate of less than 1% per year when used consistently and correctly and, when applicable, in accordance with the product label. For non-product methods (e.g., male sterility), the investigator determines what is consistent and correct use. The GSK definition is based on the definition provided by the ICH [ICH, M3 (R2) 2009].”
The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.
A female subject is eligible to participate if she is of non-child bearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as age greater than 60 or 12 months of spontaneous amenorrhea with an appropriate clinical profile [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 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

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified