Asthma
Conditions
Brief summary
A dose range-finding study to assess the efficacy and safety of multiple dose levels of AZD8630 administered via a dry powder inhaler in adults with uncontrolled asthma at risk of exacerbations, receiving medium -to -high dose inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA).
Detailed description
This is a Phase II, randomised, placebo-controlled, double-blind, dose range-finding, multi-centre study to assess the efficacy and safety of inhaled AZD8630 administered at 3 doses via an inhaler in adult patients with uncontrolled asthma, at risk of an exacerbation. The study duration up to 57 weeks for participants in the optional safety extension study and up to 17 weeks for those not included. The maximal treatment period is up to 52 weeks. This study will be conducted in approximately 220 centres in 20-25 countries. Approximately 516 patients will be randomised globally
Interventions
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Quadruple
Intervention model description
This is a parallel-group treatment study with 4 arms that is patient and Investigator blinded. Patients will be randomly assigned in a 1:1:1:1 ratio to one of the 4 treatment arms.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Principal inclusion criteria (abbreviated): 1. Patient must be 18 to 80 years of age inclusive 2. Documented physician diagnosis of asthma for at least 12 months, with objective evidence of asthma (spirometric, bronchial challenge, exercise challenge or therapeutic response) within the last 5 years 4\. Uncontrolled asthma (i.e. ACQ-6 ≥ 1.5) 5\. Pre-BD FEV1 ≥ 40% 7\. A history of asthma exacerbations within the last 12 months 8\. \& 9. Compliant with asthma background mediation, daily ePROs and daily home spirometry. 10\. BMI within the range 18-37 kg/m2 (inclusive) 11\. Female patients of child bearing potential must not be pregnant and agree to use highly effective contraception. 12\. Male patients and their female partners of childbearing potential must agree to use highly effective contraception. 13\. Capable of giving signed informed consent. Principal
Exclusion criteria
(abbreviated): 1. History of life-threatening asthma 2. Recently completed treatment for respiratory infection and/or asthma exacerbation 3. Clinically important pulmonary disease other than asthma; including but not limited to those with co-existent chronic obstructive pulmonary disease. 4. Any disorder that is not stable in the opinion of the Investigator and could: 1. Affect the safety of the patient throughout the study 2. Influence the findings of the study or their interpretation 3. Impede the patient's ability to complete the entire duration of study 5. Patients who, in the opinion of the Investigator, have evidence of active TB or are currently on treatment for active or latent TB. 6. Medical history of or treatment for hepatitis B or hepatitis C, except for cured hepatitis C 7. Patients with history of HIV infection or who test positive for HIV. 8. Congenital long QT syndrome or prolonged QTcF \> 470 ms or history of QT prolongation associated with other medications that required discontinuation of that medication. 9. Current untreated or uncontrolled arrhythmia. 10. Patients with recent myocardial infarction, unstable angina pectoris, stroke, percutaneous coronary intervention or coronary artery bypass grafting. 11. A helminth parasitic infection diagnosed that has not been treated, or has not responded to SoC therapy. 12. Current smokers, former smokers with \> 10 pack-years history, or former smokers who stopped smoking \< 6 months ago. 13. Known history of drug or alcohol abuse within 12 months, that in the Investigator's opinion would preclude participation in the study. 14. Current diagnosis of cancer or unresectable cancer that has not been in complete remission for at least 5 years. 15. Any other clinically relevant abnormal findings that in the opinion of the Investigator or medical monitor might compromise the safety of the patient in the study or interfere with evaluation of the study intervention. 16. Treatment with marketed or investigational biologics within 4 months or a minimum of 5 half-lives. 17. Treatment with Systemic steroids within 4 weeks. 18. Chronic oral or systemic CS use for asthma or for any other indication (with the exception of stable replacement therapy in adrenal insufficiency).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to first CompEx Asthma event | 12 weeks | The CompEx Asthma is a composite endpoint for exacerbations that captures asthma-worsening episodes based on combination of diary events (worsening in daily PEF, asthma symptoms and rescue medication use) plus severe asthma exacerbation events. Diary events are defined by threshold and slope criteria using the following morning/evening diary variables: * PEF * Asthma symptom score (0 to 3) * Use of rescue medication |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pre-BD FEV1 | 12 weeks | Change from baseline in pre-bronchodilator forced expiratory volume in 1 second. |
| ACQ-6: | 12 weeks | Change from baseline in the Asthma Control Questionnaire 6 (ACQ-6). The ACQ-6 has 6 questions (regarding asthma symptoms and rescue bronchodilator use). Answering the questions results in a score out of 6. A Score of 0 indicates complete control and 6 reflects severely uncontrolled disease |
| AQLQ12+ | 12 weeks | Change from baseline in the Asthma Quality of Life Questionnaire for 12 Years and Older. The AQLQ12+ includes 32 questions grouped into four domains: symptoms; activity limitations; emotional function; and, environmental stimuli. Each question is scored on a seven-point Likert scale, which ranges from 7 (no impairment) to 1 (severe impairment). The overall score is calculated as the mean of all questions, and the four domain scores are the means of the scores for the questions in the respective domains |
| SGRQ | 12 weeks | Change from baseline in the St. George's Respiratory Questionnaire. The SGRQ includes 50 questions grouped into two parts: Part 1 : Symptoms component (frequency \& severity) with a 1, 3 or 12-month recall (best performance with 3- and 12-month recall); Part 2: Activities that cause or are limited by breathlessness; Impact components (social functioning, psychological disturbances resulting from airways disease) refer to current state as the recall. |
| FeNO | 12 weeks | Change from baseline to: FeNO: Weeks 1, 2, 4, 8, and 12 |
Countries
Argentina, Belgium, Chile, China, Czechia, Denmark, France, Germany, Hong Kong, Israel, Italy, Japan, Mexico, Netherlands, Slovakia, South Africa, South Korea, Spain, Taiwan, Turkey (Türkiye), Ukraine, United Kingdom, United States
Contacts
PRINCIPAL_INVESTIGATORNjira Lugogo
Univeristy of Michigan Hospital, Ann Arbor, MI, US
Outcome results
None listed