CTRI/2024/11/076964尚未招募3 期
A randomized, double-blind, placebo-controlled, parallel-group study to assess the efficacy, safety, and tolerability of dexpramipexole administered orally for 52 weeks in participants with severe eosinophilic asthma
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 930
- 试验地点
- 14
- 主要终点
- The primary objective of the study is to demonstrate the efficacy of dexpramipexole in reducing severe asthma exacerbations. The primary endpoint of this study is the AAER over
研究概览
简要总结
This study will be a randomized, double-blind, placebo-controlled, parallel-group study in approximately 930 participants, aged greater than or equal to 12 years, with severe eosinophilic asthma and a blood eosinophil count of greater than or equal to 0.30x109/L. This study will evaluate the efficacy, safety, and tolerability of two doses of dexpramipexole (75 mg and 150 mg) administered BID. Informed consent (and assent where applicable) will be obtained from participants before the initiation of any study-specific procedures. This will be a global, multicenter study in approximately 200 centers.
At Week 52, participants may choose to continue to the long-term extension study. These participants will transition at the Week 52 Visit and will not complete the Week 56 visit.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 12.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •To be eligible to participate in this study, candidates must meet the following eligibility criteria at Screening Visit 1 or at the timepoint specified in the individual eligibility criterion listed below: Signed informed consent form and assent form, as appropriate.
- •Male or female greater than or equal to 12 years of age at Screening Visit
- •Asthma-related criteria: Documented physician diagnosis of asthma for greater than or equal to 12 months prior to Screening Visit
- •Eosinophil count of greater than or equal to 0.30x109/L at Screening Visit
- •If the initial value is between 0.250x109/L to 0.299x109/L, then this may be repeated once at an unscheduled visit (prior to Screening Visit 2).
- •Treatment of asthma, participants must satisfy all the below (items a to c): Participants who have received asthma controller medication with medium or high dose inhaled corticosteroids (ICS; greater than or equal to 500 μg/day fluticasone propionate dry powder formulation daily or clinically comparable, per GINA 2021) on a regular basis for at least 12 months prior to Screening Visit
- •Equivalent medium and high dose ICS doses are detailed in Appendix C Documented treatment with a stable dose of either medium or high dose ICS for at least 3 months prior to Screening Visit
- •The ICS may be contained within an ICS/long-acting β2 agonist (LABA) combination product.
- •As noted in Section 5.2.2, daily oral corticosteroids are an allowed concomitant medication; participants on daily oral corticosteroids must be on a stable dose for 3 months before Screening Visit
- •Use of one or more additional daily maintenance asthma controller medications according to standard practice of care is required;eg, LABA, leukotriene antagonist, theophylline, long-acting muscarinic antagonists, cromolyn/nedocromil.
- •Pre-BD FEV1 greater than or equal to 40% and less than 80% (less than 90% for participants 12 to 17 years ofage) of predicted at Screening Visit
- •Variable airflow obstruction documented with at least one of the following criteria: Bronchodilator reversibility at Screening Visit 2, as evidenced by greater than or equal to 12% and greater than or equal to 200 mL improvement in FEV1, 15 to 30 minutes following inhalation of 400 μg (four puffs) of albuterol/salbutamol (greater than or equal to 12% and greater than or equal to 160 mL for ages 12 to 17).
- •Participants who do not meet the bronchodilator reversibility inclusion criterion but have greater than or equal to 10% and greater than or equal to 160 mL reversibility, may repeat the reversibility spirometry assessment once during the Screening period, at an unscheduled visit at least 7 days prior to baseline.
- •Bronchodilator reversibility, using the criteria above, documented in the past 24 months prior to Screening Visit
- •Peak flow variation of greater than or equal to 20% over a 2-week period, documented in the past 24 months prior to Screening Visit
- •Airflow variability in clinic FEV1 greater than or equal to 20% between two consecutive clinic visits, documented in the past 24 months prior to Screening Visit
- •General medical history: Airway hyperresponsiveness (provocative concentration causing a 20% fall in FEV1 of methacholine less than 8 mg/mL) documented in the past 24 months prior to Screening Visit
- •ACQ-6 greater than or equal to 1.5 at Screening Visit
- •Documented history of at least two asthma exacerbations requiring treatment with systemic corticosteroids (intramuscular, intravenous, or oral) within the past 12-month period prior to Screening Visit
- •Negative urine pregnancy test for women of childbearing potential (WOCBP after menarche) at the Screening and Baseline visits.
- •WOCBP (after menarche) must use either of the following methods of birth control, from Screening Visit 1 through the End of Study Visit: A highly effective form of birth control confirmed by the investigator.
- •Highly effective forms of birth control include true sexual abstinence, a vasectomized sexual partner, Implanon, female sterilization by tubal occlusion, any effective intrauterine device IUD, IUD intrauterine system IUS, Levonorgestrel IUS, or oral contraceptive.
- •Two protocol acceptable methods of contraception in tandem.
- •Women not of childbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) or who are postmenopausal.
- •Women will be considered postmenopausal if they have been amenorrheic for greater than or equal to 12 months prior to the planned date of the Baseline Visit without an alternative medical cause.
- •The following age specific requirements apply: Women less than 50 years old will be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatment and follicle stimulating hormone levels in the postmenopausal range.
- •Women greater than or equal to 50 years old will be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatment.
排除标准
- •Study participant candidates will be excluded from study entry if any of the following exclusion criteria exist at Screening Visit 1 or at the timepoint specified in the individual criterion listed below: Asthma-related criteria: A participant who experiences a severe asthma exacerbation (defined as a deterioration of asthma that results in emergency treatment, hospitalization due to asthma, or treatment with systemic corticosteroids) at any time from 4 weeks prior to Screening Visit 1 up to and including the Baseline Visit.
- •Participants who experience an asthma exacerbation during the Screening/Run-in Period may remain in Screening and proceed with study visits 14 days after they have completed their course of oral steroids or returned to their pre-Screening Visit maintenance dose of oral steroids and the investigator considers participant has returned to baseline status.
- •Current diagnosis of diseases which may confound interpretation of this study’s findings such as allergic bronchopulmonary aspergillosis, eosinophilic granulomatosis with polyangiitis, eosinophilic gastrointestinal diseases, hypereosinophilic syndrome, or lung diseases (eg, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis).
- •Participants in India will have a chest x-ray performed during screening.
- •Participants with evidence of chronic tuberculosis or extensive fibrosis are excluded.
- •Respiratory infection: Upper or lower respiratory tract, sinus, or middle ear infection within the 4 weeks before Screening Visit
- •Prohibited medications/procedures: Treatment with a biologic investigational drug in the last 5 months prior to Screening Visit
- •Treatment with non-biologic investigational drugs in the previous 30 days or five-half-lives prior to Screening Visit 1, whichever is longer.
- •Treatment with GSK3511294 (long-acting anti-interleukin [IL]-5) in the past 12 months.
- •Treatment with any of the following monoclonal antibody therapies within 120 days prior to Baseline: benralizumab, dupilumab, mepolizumab, reslizumab, omalizumab, tezepelumab, or tralokinumab.
- •Treatment with pramipexole (Mirapex®) within 30 days of Baseline.
- •Treatment with selected drugs known to have a substantial risk of neutropenia in the past 30 days prior to Screening Visit 1 (see Appendix A).
- •Bronchial thermoplasty procedure in the past 12 months prior to Screening Visit 1 or planned during the coming year.
- •General medical history Weight less than 40 kg at Screening Visit
- •Current smoking within 12 months prior to Screening Visit 1 or a smoking history of greater than 10 pack-years.
- •Smoking includes tobacco, vaping, and/or marijuana use.
- •Known or suspected alcohol or drug abuse Uncontrolled severe hypertension: systolic blood pressure greater than 180 mmHg or diastolic blood pressure greater than 110 mmHg prior to the Baseline Visit despite anti-hypertensive therapy.
- •History of malignancy that required surgery (excluding local and wide-local excision), radiation therapy and/or systemic therapy during the 5 years prior to the Baseline Visit.
- •History of human immunodeficiency virus (HIV) infection or chronic infection with hepatitis B or C.
- •A helminth parasitic infection diagnosed within 24 weeks prior to Screening Visit 1 that has not been treated with or has failed to respond to standard of care (SoC) therapy.
- •Medical or other condition likely to interfere with participant’s ability to undergo study procedures, adhere to visit schedule, or comply with study requirements.
- •Known or suspected noncompliance with medication.
- •Unwillingness or inability to follow the procedures outlined in the protocol.
- •Clinical safety labs Absolute neutrophil count less than 2.000x109/L at Screening Visit 1 or Screening Visit
- •Renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73m2 at Screening Visit 2 (using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula [Levey et al, 2009] for age greater than or equal to 18 years at screening; using the Bedside Schwartz [Schwartz and Work, 2009] eGFR formula for age less than 18).
- •Active liver disease defined as any known current infectious, neoplastic, or metabolic pathology of the liver or unexplained elevations in alanine aminotransferase (ALT), aspartate aminotransferase (AST), greater than 3x the upper limit of normal (ULN), or total bilirubin greater than 2x ULN at Screening Visit 2 confirmed by a repeat abnormal measurement of the relevant value(s), at least 1 week apart.
- •Cardiac safety History of New York Heart Association class IV heart failure or last known left ventricular ejection fraction less than 25%.
- •History of major adverse cardiovascular event (MACE) within 3 months prior to the Baseline Visit.
- •History of cardiac arrhythmia within 3 months prior to the Baseline Visit that is not controlled by medication or via ablation.
- •History of long QT syndrome.
- •Corrected QT interval by Fridericia (QTcF) interval greater than 450 ms for males and greater than 470 ms for females at Screening Visit 2 or QTcF greater than or equal to 480 ms for participants with bundle branch block.
- •Clinically important abnormalities in resting ECG that may interfere with the interpretation of QTcF interval changes at Screening Visit 2, including resting heart rate less than 45 beats per minute (bpm) or greater than 100 bpm.
- •Pregnancy/Lactation Pregnant women or women breastfeeding.
- •Males who are unwilling to use an acceptable method of birth control during the entire study period (ie, condom with spermicide).
结局指标
主要结局
The primary objective of the study is to demonstrate the efficacy of dexpramipexole in reducing severe asthma exacerbations. The primary endpoint of this study is the AAER over
时间窗: 52 weeks
次要结局
- To demonstrate the efficacy of dexpramipexole on pulmonary function(Pre-BD FEV1, absolute change from baseline, averaged across visits)
- To demonstrate the efficacy of dexpramipexole on asthma control & quality of life(Asthma Control Questionnaire-6 ACQ-6, change from baseline, averaged across visits)
- To evaluate the effect of dexpramipexole on blood eosinophils(Standardized version of the Asthma Quality of Life Questionnaire for 12 years & older AQLQ Plus 12 change from baseline)
- Annualized rate over of severe exacerbations requiring an emergency department ED visit or hospitalization.(52 weeks)
- AAER
- AEC, change from baseline(Week 52)
- Forced vital capacity FVC, change from baseline, averaged over(Weeks 36, 44, & 52)
- FVC, change from baseline
- Post bronchodilator FEV1, change from baseline to
- Peak expiratory flow PEF, change from baseline to(Week 52)
- Time to first severe asthma exacerbation. Total asthma symptom score, change from baseline to(Week 52)
- The EuroQol 5-dimensional questionnaire EQ 5D 5L, change from baseline to(Week 52)
研究者
研究点 (14)
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