Asthma MedDRA version: 20.0 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Product Name: tralokinumab
Product Code: CAT-354
Pharmaceutical Form: Solution for injection
INN or Proposed INN: tralokinumab
CAS Numbe
Sponsors
AstraZeneca AB R&D Mölndal
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Age 18-75 years of age at the time of screening (Visit 1). 2) Written informed consent 3) Body mass index (BMI) between 16-40 kg/m2 at Visit 1. 4) Documented physician-diagnosed asthma for at least 12 months prior to Visit 1 and EITHER - Proof of postbronchodilator reversibility of FEV1 = 12% and = 200 mL to a SABA documented within 36 months prior to Visit 1; OR - Proof of a positive response (PC20 = 8 mg/mL) to a methacholine or histamine challenge documented within 36 months prior to Visit 1; OR - A postbronchodilator increase in FEV1 = 12% and = 200 mL at Visit 1. 5) Subjects must have received an asthma controller regimen consistent with that described at Step 4 or 5 of the GINA guidelines (GINA, 2009) for at least 6 of the 12 months prior to Visit 1 and must have used physician prescribed high-dose ICS in combination with LABA for at least 30 days prior to Visit 1 6) For subjects receiving an alternative combination of ICS/LABA prior to Visit 1, a willingness to switch to fluticasone/salmeterol either as a DPI at a dose of 500/50 µg, one inhalation twice per day, or as an MDI at a dose of 230 µg/21 µg, 2 inhalations twice per day, once eligibility has been confirmed at Visit 2. 7) Where applicable, the dose of other asthma controller medications (leukotriene modifiers, theophylline, OCS, or cromones) must have been stable for at least 30 days prior to Visit 1. 8) Subjects must have a history of at least 2 but no more than 6 documented asthma exacerbation events within the 12 months prior to Visit 1. 9) At both Visits 1 and 4, subjects must have at least one of the following; a morning prebronchodilator FEV1 value of between 40% and 80% predicted or an ACQ-6 score for the preceding week of = 1.5. 10) A chest x-ray taken during the screening/run-in period or within the 12 months before Visit 1 that, according to the investigator, is normal for an asthmatic subject and excludes significant alternative respiratory disease. 11) Females of childbearing potential who are sexually active with a nonsterilized male partner must use highly effective contraception from screening, and must agree to continue using such precautions through Week 75 of the study. - A highly effective method of contraception is defined as one that results in a low failure rate (ie, less than 1% per year) when used consistently and correctly. 12) Nonsterilized males or sterilized males who are = 1 year post-vasectomy who are sexually active with a female partner of childbearing potential must use a highly effective method of contraception (see Table 4.2.1-1) from Day 1 through Week 75. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 350 F.1.3
Exclusion criteria
Exclusion criteria: 1) Employee of the clinical study site or any other individuals directly involved with the conduct of the study, or immediate family members of such individuals. 2) Pregnant or breastfeeding women. 3) Individuals who are legally institutionalized. 4) Subjects unable to demonstrate acceptable inhaler and peak flow meter/spirometry techniques as judged by the investigator. 5) Any concomitant respiratory disease that in the opinion of the investigator and/or medical monitor will interfere with the evaluation of the investigational product. 6) Concurrent enrollment in another clinical study where the subject is receiving an investigational product. 7) Previous receipt of tralokinumab. 8) Receipt of any marketed or investigational biologic agent within 4 months or 5 half-lives prior to Visit 1, whichever is longer 9) Receipt of any investigational nonbiologic agent within 3 months or 5 half-lives prior to Visit 1, whichever is longer 10) Subjects who have received a live or live attenuated vaccine within 4 weeks prior to Visit 1. 11) Use of systemic immunosuppressive medication within 3 months prior to Visit 1. 12) Current use of any oral or ophthalmic ß-adrenergic antagonist. 13) Occurrence of an asthma exacerbation event requiring a burst of systemic corticosteroids from 30 days prior to Visit 1, up to and including Visit 4. 14) Known history of allergy or reaction to any component of the investigational product formulation or history of anaphylaxis following any biologic therapy. 15) Known exposure to inhaled occupational agents or fumes with an established diagnosis of occupational asthma. 16) Current tobacco smoking or a history of tobacco smoking = 10 pack-years. 17) Previous medical history or evidence of an uncontrolled intercurrent illness that in the opinion of the investigator and/or medical monitor may compromise the safety of the subject in the study or interfere with evaluation of the investigational product or reduce the subject’s ability to participate in the study. 18) Any clinically relevant abnormal findings in physical examination, electrocardiogram (ECG), vital signs, hematology, clinical chemistry, or urinalysis during screening/runin period, which in the opinion of the investigator or medical monitor may compromise the safety of the subject in the study or interfere with evaluation of the investigational product or reduce the subject’s ability to participate in the study. 19) Evidence of active liver disease, including jaundice or aspartate transaminase, alanine transaminase, or alkaline phosphatase greater than twice the upper limit of normal. 20) History of a clinically significant infection from 30 days prior to Visit 1, up to and including Visit 4. 21) Subjects who in the opinion of the investigator have evidence of active TB, either treated or unt
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate two SC treatment regimens of 300 mg tralokinumab compared with placebo by assessing the effect on asthma exacerbation rate over 52 weeks in adults with uncontrolled, severe asthma requiring high-dose ICS and LABA with or without additional asthma controller medications.; Secondary Objective: 1) To evaluate the safety and tolerability of tralokinumab. 2) To evaluate the effect of tralokinumab on pulmonary function: clinic spirometry, including pre- and post-bronchodilator FEV1, forced expiratory volume in 6 seconds (FEV6), FVC, inspiratory capacity (IC); and PEF and FEV1 measured at home. 3) To evaluate the effect of tralokinumab on Patient Reported Outcomes: Asthma Control Questionnaire (6-item version; ACQ-6) score, HRQoL using Asthma Quality of Life Questionnaire Standardised Version (AQLQ[S]), and EQ-5D. 4) To evaluate the effect of tralokinumab on asthma symptoms using the Assessing Symptoms of Moderate-to-severe Asthma (ASMA) diary and use of rescue medication. 5) To describe the pharmacokinetics (PK) and immunogenicity of tralokinumab. ; Primary end point(s): The primary objective of this study is to evaluate the effect of two SC treatment regimens of 300 mg tralokinumab compared with placebo by assessing the asthma exacerbation rate over 52 weeks in adults with uncontrolled, severe asthma requiring high-dose ICS and LABA with or without additional controller medications. ;Timepoint(s) of evaluation of this end point: 52 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) To evaluate the safety and tolerability of tralokinumab. 2) To evaluate the effect of tralokinumab on pulmonary function: clinic spirometry, including pre- and post-bronchodilator FEV1, forced expiratory volume in 6 seconds (FEV6), FVC, inspiratory capacity (IC); and PEF and FEV1 measured at home. 3) To evaluate the effect of tralokinumab on Patient Reported Outcomes: Asthma Control Questionnaire (6-item version; ACQ-6) score, HRQoL using Asthma Quality of Life Questionnaire Standardised Version (AQLQ[S]), and EQ-5D. 4) To evaluate the effect of tralokinumab on asthma symptoms using the Assessing Symptoms of Moderate-to-severe Asthma (ASMA) diary and use of rescue medication. 5) To describe the pharmacokinetics (PK) and immunogenicity of tralokinumab. ;Timepoint(s) of evaluation of this end point: 52 weeks. Safety follow up at 74 weeks. | — |
Countries
Argentina, Brazil, Canada, Chile, Czech Republic, France, Germany, Korea, Republic of, Mexico, Philippines, Poland, Russian Federation, Spain, United Kingdom, United States
Contacts
Public ContactInformation Centre
AstraZeneca AB
Outcome results
None listed