CTRI/2025/08/093490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
- 1,395
- 试验地点
- 12
- 主要终点
- Annualized rate of severe asthma exacerbations over 52 weeks.
研究概览
简要总结
This study will be a randomized, double-blind, placebo-controlled, parallel-group study in approximately 1395 participants, aged greater than and equal to 12 years, with severe eosinophilic asthma. This study will evaluate the efficacy, safety, and tolerability of two doses of dexpramipexole (75 mg and 150 mg) administered BID. This will be a global, multicenter study in approximately 300 centers. The primary objective of the study is to demonstrate the efficacy of dexpramipexole in reducing severe asthma exacerbations. Note enrollment of participants of 12 to 17 years of age is closed. This study will assess the efficacy and safety of dexpramipexole as an adjunctive oral therapy in participants with inadequately controlled asthma with an eosinophilic phenotype and a history of asthma exacerbations.
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
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •1.Signed informed consent form and assent form, as appropriate
- •Male or female greater than or equal to eighteen years of age at Screening Visit
- •Asthma-related criteria 3.Documented physician diagnosis of asthma for greater than or equal to 12 months prior to Screening Visit
- •4.Treatment of asthma, participants must satisfy all the below (items a to c) a)Participants who have received asthma controller medication with medium or high dose inhaled corticosteroids (ICS greater than or equal to 500 mcg per day fluticasone propionate dry powder formulation daily or clinically comparable, per Global Initiative for Asthma (GINA) 2021) on a regular basis for at least 12 months prior to Screening Visit 1.b)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 LABA (long acting beta2 agonist) combination product.
- •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
- •b) 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 LABA (long-acting Beta2 agonist) combination product.
- •c)Use of one of more additional daily maintenance asthma controller medications according to standard practice of care is required.
- •Use of a stable dose of any additional asthma controller medications must be documented for at least 3 months prior to Screening Visit
- •Pre-BD FEV1 greater than or equal to 40 percentage and less than 80 percentage of predicted at Screening Visit
- •Variable airflow obstruction documented with at least one of the following criteria:
- •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
- •General medical history
- •WOCBP must use either of the following methods of birth control, from Screening Visit 1 through the End of Study Visit 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 would 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 would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatment.
- •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 intrauterine system, Levonorgestrel Intrauterine system, or oral contraceptive.
排除标准
- •Asthma-related criteria 1.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
- •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.
- •2.Current diagnosis of diseases which may confound interpretation of this studys findings such as allergic bronchopulmonary aspergillosis, eosinophilic granulomatosis with polyangiitis, eosinophilic gastrointestinal diseases, hypereosinophilic syndrome, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis.
- •3.Respiratory infection: Upper or lower respiratory tract, sinus, or middle ear infection within the 4 weeks before Screening Visit
- •4.For participants aged twelve to seventeen years old, AEC of less than 0.15 by 10 mine per L at Screening Visit
- •Note enrollment of participants of twelve to seventeen years of age is closed.
- •Prohibited medications/procedures 5.Treatment with a biologic investigational drug in the last five 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 IL 5) in the past 12 months.
- •6.Treatment with any of the following monoclonal antibody therapies within 120 days prior to Baseline Visit benralizumab, dupilumab, mepolizumab, reslizumab, omalizumab, tezepelumab, or tralokinumab.
- •7.Treatment with pramipexole (Mirapex) within 30 days of Baseline Visit.
- •8.Treatment with selected drugs known to have a substantial risk of neutropenia in the past 30 days prior to Screening Visit
- •9.Bronchial thermoplasty procedure in the past 12 months prior to Screening Visit 1 or planned during the coming year.
- •11.Current smoking within the 12 months prior to Screening Visit 1 or a smoking history of greater than10 pack years.
- •Smoking includes tobacco, vaping, and/or marijuana use.
- •12.Known or suspected alcohol or drug abuse 13.Uncontrolled severe hypertension systolic blood pressure greater than 180 mmHg or diastolic blood pressure greater than110 mmHg prior to the Baseline Visit despite antihypertensive therapy.
- •14.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.
- •15.History of human immunodeficiency virus (HIV) infection or chronic infection with hepatitis B or C.
- •16.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.
- •17.Medical or other condition likely to interfere with participants ability to undergo study procedures, adhere to visit schedule, or comply with study requirements.
- •18.Known or suspected noncompliance with medication.
- •19.Unwillingness or inability to follow the procedures outlined in the protocol.
- •Clinical safety labs 20.Absolute neutrophil count (ANC) less than 2.000 by 10 nine per L at Screening Visit 1 or Screening Visit
- •21.Renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) less than60 mL min 1.73m square at Screening Visit 2 (using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula [Levey et al, 2009].
- •22.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 than3x the upper limit of normal (ULN), or total bilirubin greater than2x ULN at Screening Visit 2 confirmed by a repeat abnormal measurement of the relevant value(s), at least 1 week apart.
- •Cardiac safety 23.History of New York Heart Association class IV heart failure or last known left ventricular ejection fraction less than25percentage.
- •24.History of major adverse cardiovascular event (MACE) within 3 months prior to the Baseline Visit.
- •25.History of cardiac arrhythmia within 3 months prior to the Baseline Visit that is not controlled by medication or via ablation.
- •26.History of long QT syndrome.
- •27.Corrected QT interval by Fridericia (QTcF) interval greater than450 ms for males and greater than470 ms for females at Screening Visit 2 or QTcF greater than or equal to 480 ms for participants with bundle branch block.
- •28.Clinically important abnormalities in resting ECG that may interfere with the interpretation of QTcF interval changes at Screening Visit 2, including heart rate less than45 beats per minute (bpm) or greater than100 bpm.
- •Pregnancy/Lactation 29.Pregnant women or women breastfeeding 30.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
Annualized rate of severe asthma exacerbations over 52 weeks.
时间窗: Day 1 (baseline, pre-dose) through Week 52
A severe exacerbation was defined as a deterioration of asthma requiring: use of systemic corticosteroids for greater than=3 days; or hospitalization or emergency room visit because of asthma, requiring systemic corticosteroids; or death due to asthma.
时间窗: Day 1 (baseline, pre-dose) through Week 52
次要结局
- Absolute Change in pre bronchodilator forced expiratory volume (Pre BD FEV)one from Baseline. The absolute change from baseline in pre bronchodilator forced expiratory volume, averaged across visits at Weeks 36, 44, and 52.
- Change From Baseline in Asthma Control Questionnaire 6 (ACQ 6)(Asthma Control Questionnaire-6 (ACQ 6), change from baseline, averaged across visits at Weeks 36, 44, and 52.)
- Change in Standardized version of the Asthma Quality of Life Questionnaire for 12 years and older (AQLQ Plus 12) from baseline to Week 52.(Day 1 (baseline, pre dose) through Week 52)
- Annualized rate of severe exacerbations requiring an emergency department visit or hospitalization over 52 weeks.(Day 1 (baseline, pre dose) through Week 52)
- Annualized Rate of severe exacerbations from Week 4 to Week 52(Week 4 through Week 52)
- Average change in absolute eosinophil count (AEC)(Day 1 (baseline, pre dose) Weeks 36, 44, 52)
- Average change from baseline in forced vital capacity (FVC)(Day 1 (baseline, pre dose), Weeks 36, 44, 52)
- Change from baseline in forced vital capacity (FVC)(Day 1 (baseline, pre dose), Weeks 4, 12, 20,28 36, 44, 52)
- Change from baseline in Postbronchodilator FEVone(Day 1 (baseline, pre-dose) through Week 52)
- Change from baseline in peak expiratory flow (PEF)(Day 1 (baseline, pre dose) through Week 52)
- Time to first severe asthma exacerbation(Up to Week 52)
- Change from baseline in total asthma symptom score(Day 1 (baseline, pre dose) through Week 52)
- Change from baseline in the EuroQol five dimensional questionnaire (EQ 5D 5L)(Day 1 (baseline, pre dose) through Week 52)
研究者
研究点 (12)
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