2023-509243-27-00招募中2 期
A Phase 2a, Randomised, Double-Blind, Placebo-Controlled Study to Assess Efficacy and Safety of Atuliflapon Given Orally Once Daily for Twelve Weeks in Adults with Moderate to Severe Uncontrolled Asthma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 431
- 试验地点
- 66
- 主要终点
- Time to first CompEx Asthma event
研究概览
简要总结
To evaluate the clinical efficacy of Atuliflapon as compared to placebo in adult participants with moderate-to-severe uncontrolled asthma
研究设计
- 分配方式
- Randomized
- 主要目的
- Follow-up period
- 盲法
- Double (Carer, Investigator, Subject, Analyst, Monitor)
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Lead-in PK Cohort – Recruitment Completed: Provision of signed informed consent prior to any study-specific procedures
- •Part 1: Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of samples for optional genetic research that supports Genomic Initiative
- •Lead-in PK Cohort – Recruitment Completed: Participant is willing and able to follow study procedures and restrictions
- •Lead-in PK Cohort – Recruitment Completed: Bodyweight 50 to 120 kg (inclusive) and BMI 18 to 32 kg/m2 (inclusive) at Screening (Visit 1)
- •Lead-in PK Cohort – Recruitment Completed: 18 to 55 years of age inclusive at the time of signing the ICF at Screening (Visit 1)
- •Lead-in PK Cohort – Recruitment Completed: Documented evidence of asthma
- •Part 1: Morning pre-BD FEV1 between ≥ 40% and ≤ 85% predicted at Screening (Visit 1) and Visit 3
- •Part 1: Documented history of ≥ 1 severe asthma exacerbation within 1 year prior to Screening (Visit 1)
- •Part 1: Treated with low dose ICS-LABA or medium-high dose ICS alone or in combination with LABA at a stable dose for at least 3 months prior to Screening (Visit 1). (The ICS can be contained within an ICS-LABA fixed dose combination product). -Treatment with additional asthma controller therapies (eg, LAMA) at a stable dose ≥ 3 months prior to Screening (Visit 1) is allowed. Treatment with LTRAs or 5-LO inhibitors is not allowed
- •Part 1: An ACQ-6 score ≥ 1.5 at Screening (Visit 1) and at Visit 3
- •Lead-in PK Cohort – Recruitment Completed: Documented asthma diagnosis ≥ 12 months prior to Screening (Visit 1)
- •Part 1: Body weight ≥ 40 kg and BMI < 35 kg/m2
- •Lead-in PK Cohort – Recruitment Completed: Able to perform acceptable lung function testing for FEV1 according to ATS/ERS 2019 acceptability criteria
- •Part 1: Documented evidence of asthma
- •Lead-in PK Cohort – Recruitment Completed: Morning pre-BD FEV1 ≥ 40% predicted at Screening (Visit 1) and Visit 2
- •Lead-in PK Cohort – Recruitment Completed: Treated with low dose ICS-LABA or medium-high dose ICS alone or in combination with LABA at a stable dose for at least 3 months prior to Screening (Visit 1). (The ICS can be contained within an ICS-LABA fixed dose combination product) -Treatment with additional asthma controller therapies (eg, LAMA) at a stable dose ≥ 3 months prior to Screening (Visit 1) is allowed. Treatment with LTRAs or 5-LO inhibitors is not allowed (see exclusion criteria)
- •Part 1: Participant is willing and able to follow study procedures and restrictions
- •Part 1: Participant must be 18 to 80 years of age inclusive, at the time of signing the ICF
- •Part 1: Able and willing to comply with the requirements of the CSP including ability to read, write, be fluent in the translated language of all participants facing questionnaires used at site, and use electronic devices, eg, eCOA device and spirometry
- •Part 1: At least 80% compliance with usual asthma background medication during run-in period (from Visit 2 to Visit 3) based on the daily asthma ePROs
- •Part 1: Minimum 80% compliance with daily eCOA assessments. Compliance is defined as completing the daily ePRO questions and PEF measurement at least 80% of the time during the run-in period and during the 14 days preceding Visit 3
- •Part 1: For women of childbearing potential, a negative serum pregnancy test at Screening (Visit 1) and negative urine pregnancy test at Visit 3
- •Part 1: Documented physician-diagnosed asthma ≥ 12 months prior to Screening (Visit 1)
- •Part 1: Contraceptive use by female participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. There are no restrictions on male participants or their female partners. Please refer to the protocol for the full list of inclusion criteria
- •Lead-in PK Cohort – Recruitment Completed: Able and willing to comply with the requirements of the CSP including ability to read, write, be fluent in the translated language of all participants facing questionnaires used at site, and use electronic devices (eg, spirometer)
- •Part 1: Able to perform acceptable lung function testing for FEV1 according to ATS/ERS 2019 acceptability criteria
- •Lead-in PK Cohort – Recruitment Completed: Participant's influenza/pneumonia vaccination is up to date as per local guidelines prior to Visit 2
- •Lead-in PK Cohort – Recruitment Completed: For female participants, a negative serum pregnancy test at Screening (Visit 1) and a negative urine pregnancy test prior to administration of study intervention (Visit 2)
- •Lead-in PK Cohort – Recruitment Completed: Contraceptive use by female participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. There are no restrictions on male participants or their female partners
- •Part 1 Capable of giving signed informed consent
排除标准
- •A severe asthma exacerbation within 8 weeks of Screening (Visit 1) or within 12 weeks of randomisation (Visit 3)
- •Participants with a recent history of, or who have a positive test for, infective hepatitis or unexplained jaundice, or participants who have been treated for hepatitis B, hepatitis C, or HIV. For the hepatitis B testing (HBsAg, anti-HBs, and anti-HBc), any of the following would exclude the participant from the study: − Participants positive for HBsAg. − Participants positive for anti-HBc
- •Participants who, as judged by the Investigator, have evidence of active TB, either treated or untreated, or latent TB without completion of an appropriate course of treatment or appropriate ongoing prophylactic treatment. Evaluation will be according to the local standard of care as determined by local guidelines and may consist of medical history and physical examinations, chest X-ray, or TB test (eg, purified protein derivative or QuantiFERON® test).
- •Abnormal findings identified on physical examination, ECG, or laboratory testing include, but are not limited to: − ALT or AST ≥ 2 × ULN. − TBL ≥ 1.5 × ULN (unless due to Gilbert's disease). − Evidence of chronic liver disease. − Abnormal vital signs, after 5 minutes of supine or sitting rest (confirmed by one controlled measurement), defined as any of the following: o SBP < 80 mmHg or ≥ 150 mmHg. o DBP < 50 mmHg or ≥ 95 mmHg. o Pulse < 45 or > 100 beats per minute. − Signs of pulmonary oedema or volume overload. − Any clinically significant rhythm, conduction, or morphology abnormalities in the ECG including but not limited to QTcF > 450 ms. Please refer to the protocol for the full list of exclusion criteria
- •A positive test result of an approved antigen test (confirmed by a positive RT-PCR test) or a positive RT-PCR test for SARS-CoV-2, the virus responsible for COVID-19
- •Participants with a significant COVID-19 illness within 6 months of enrolment: − Participants with a diagnosis of COVID-19 pneumonia based on radiological assessment. − Participants with a diagnosis of COVID-19 requiring hospitalization and/or oxygen supplementation therapy
- •Clinically important pulmonary disease other than asthma eg, active lung infection, COPD, bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung cancer, history or planned lung lobectomy, alpha-1 anti-trypsin deficiency, primary ciliary dyskinesia, Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis and hyper-eosinophilic syndrome
- •Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric, or major physical impairment that is not stable in the opinion of the investigator and could: − Affect the safety of the participant throughout the study. − Influence the findings of the study or the interpretation. − Impede the participant's ability to complete the entire duration of study
- •Any clinically significant cardiac disease: − Acute coronary syndrome (acute myocardial infarction, unstable angina) or coronary intervention with percutaneous coronary intervention/coronary artery bypass surgery within 6 months. − Heart failure NYHA II-IV. − Untreated high degree atrioventricular-block (≥ 3:1 conduction rate/Grade III block)/ significant sinus node dysfunction/pause or therapy requiring tachyarrhythmia. − History or family history of long QT-syndrome. − History of QT prolongation associated with other medications that required discontinuation of that medication. − Hypertrophic cardiomyopathy or clinically significant valvular heart disease. − Stroke within 3 months of Screening (Visit 1)
- •History of severe renal disease (CKD stage 4 or 5) or history of creatinine clearance < 30 mL/min × m2 calculated using Cockcroft-Gault equation
- •Severe hepatic impairment (Child-Pugh class C)
- •Previous hepatotoxicity related to zileuton or LTRAs (eg, montelukast)
结局指标
主要结局
Time to first CompEx Asthma event
Time to first CompEx Asthma event
次要结局
- Clinical efficacy endpoints: Change from baseline in: 1 pre-BD FEV1: Week 4, and Week 12 2 SGRQ: Week 4, and Week 12
- Clinical efficacy endpoints: Change from Baseline in: 1 ACQ-6: Week 4, 8, 12, and average over the 12-weeks 2 average morning and average evening PEF: Week 4, 8, 12, and average over 12-weeks 3 daily asthma symptom score (total, daytime, and night-time): Week 4, 8, 12, and average over the 12-weeks
- Clinical efficacy endpoints: 1 time to first severe asthma exacerbation 2 event status (CompEx Asthma event yes/no)
- To evaluate the PK of Atuliflapon: 1 Atuliflapon plasma concentrations and PK parameters 2 Atuliflapon plasma concentrations: pre-dose samples at Baseline, Week 4, and Week 12
- Safety Endpoints: Safety and tolerability evaluations using AEs, vital sign measures, clinical laboratory assessments, ECG and C-SSRS. For full information please refer to the protocol
研究者
AstraZeneca Clinical Study Information Centre
Scientific
AstraZeneca AB
研究点 (66)
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