A Phase III, Multicentre, Randomised, Double-blind, Chronic-dosing, Parallel-group, Placebo-controlled Study to Evaluate the Efficacy and Safety of Two Dose Regimens of MEDI3506 in Participants with Symptomatic Chronic Obstructive Pulmonary Disease (COPD) with a History of COPD Exacerbations (TITANIA)
- Conditions
- J449 Chronic obstructive pulmonary disease, unspecifiedChronic obstructive pulmonary disease, unspecifiedJ449
- Registration Number
- PER-001-22
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- In enrollment
- Sex
- All
- Target Recruitment
- 42
Participants are eligible to be included in the study only if all of the following criteria apply:
Age
1Participant must be = 40 years of age at the time of signing the ICF.
Type of Participant and Disease Characteristics
2Documented diagnosis of COPD for at least one year prior to enrolment.
3Post BD FEV1/FVC < 0.70 and post-BD FEV1 >20% of predicted normal value (as assessed by central spirometry at screening).
4Documented history of = 2 moderate or = 1 severe COPD exacerbations within 12 months prior to enrolment:
(a)An exacerbation is considered moderate if it required treatment with systemic corticosteroids and/or antibiotics, and severe if it required hospitalisation. Note: hospitalisation is defined as an inpatient admission = 24 hours in the hospital, in an observation area, emergency department, or other equivalent healthcare facility depending on the country and healthcare system.
(b) At least one qualifying exacerbation should have been treated with systemic corticosteroids.
(c)Events treated with antibiotics alone qualify as a moderate exacerbation only when antibiotic was specifically prescribed for worsening of COPD symptoms.
(d)Previous exacerbations should be confirmed to have occurred while the participant was on stable dual or triple (ICS/LABA/LAMA) maintenance inhaled therapy for COPD and not as a result of a gap or step down in the treatment.
(e)At least one qualifying exacerbation should have occurred while on the most recent stable uninterrupted therapy (see inclusion criterion 5(a) and section 6.5.2) prior to enrolment.
5Documented optimised treatment with COPD inhaled maintenance therapy (ICS/LABA/LAMA triple therapy, or dual therapy if triple is not indicated or contraindicated) and at a stable dose for at least 3 months prior to enrolment. During this period:
(a)Individual component changes or switches between devices are allowed as long as the participant remains on the same class therapies in equivalent doses .
(b)Short-term changes in background treatment regimen during COPD exacerbation are acceptable.
(c)Short-acting muscarinic antagonist taken at regular scheduled interval (at a minimum frequency of 3 times daily) will be considered equivalent to LAMA.
(d)If participant is being treated with any oral COPD maintenance therapy (eg, macrolides, xanthines, roflumilast), these treatments must also be stable for at least 3 months prior to enrolment (see Section 6.5.2).
6Smoking history of = 10 pack-years:
(a)Former smokers will be defined as participants who are currently not smoking and with smoking cessation = 6 months prior to screening with an intention to quit permanently.
(b)Current smokers will be defined as participants who are currently smoking tobacco (at least one cigarette per day on average during the past 7 days) and are not currently participating in smoking cessation.
(c)Electronic cigarette (e-cigarette) use does not contribute to the pack-year count for eligibility.
7CAT total score = 10, with each of the phlegm (sputum) and cough items with a score = 2, at both screening (V1) and randomisation (V2).
8At least 70% daily PRO completion during the entire screening period, with at least 50% daily PRO completion in the 14-day period prior to ra
Diagnostic Assessments
33Any clinically significant abnormal findings in physical examination, vital signs, ECG, or laboratory testing during the screening period, which in the opinion of the investigator may put the participant at risk because of his/her participation in the study, or may influence the results of the study, or the participant’s ability to complete the entire duration of the study. If abnormal findings suggest a transient effect, participants may be retested at the discretion of the investigator prior to randomisation.
Other Exclusions
34Active vaping of any products (eg, nicotine, tetrahydrocannabinol [THC]) within the 6 months prior to randomisation and during the study. Note: active vaping is defined as at least one vape a day on average, over last 7 days.
35History of alcohol or drug abuse within the past year, which may compromise the study data interpretation, as judged by investigator or AstraZeneca study physician.
36Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
37Participants undergoing donation of blood, plasma, or platelets within the past 90 days prior to enrolment.
5.2Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1Clinically important pulmonary disease other than COPD (eg, active lung infection, clinically significant bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung cancer, alpha 1 anti-trypsin deficiency, and primary ciliary dyskinesia).
2Radiological findings suggestive of a respiratory disease other than COPD that is contributing to the participant’s respiratory symptoms. Radiological findings of solitary pulmonary nodules without appropriate follow up and demonstration of stability as per standard of care, or findings suggestive of acute infection.
3Current diagnosis of asthma according to the GINA or other accepted guidelines, prior history of asthma, or asthma-COPD overlap . Childhood history of asthma is allowed and defined as asthma diagnosed and resolved (ie, not requiring the use of any maintenance or rescue medication) before the age of 18.
4Any unstable disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric disorder, major physical and/or cognitive impairment that, in the opinion of the investigator, could:
(a)Affect the safety of the participant throughout the study.
(b)Influence the findings of the study or their interpretation.
(c)Impede the participant’s ability to complete the entire duration of the study and/or comply with the study visit schedule and procedures.
5COPD exacerbation, within 2 weeks prior to randomisation, that was treated with systemic corticosteroids and/or antibiotics, and/or led to hospitalisation (based on last dose of corticosteroids or antibiotics, or last date of hospitalisation, whichever occurred later).
6
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method rate ratio<br> NAME OF THE RESULT: Annualised rate of moderate to severe COPD exacerbations in former smokers.<br> PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE<br> PRIMARY RESULT: while-on-treatment
- Secondary Outcome Measures
Name Time Method