Prevention of Asthma Exacerbations Using Dupilumab in Urban Children and Adolescents (PANDA) (CAUSE-01)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 240
- 试验地点
- 8
- 主要终点
- Number of asthma exacerbations during the 12-month treatment period
研究概览
简要总结
This is a multi-center, double-blind, placebo-controlled, randomized trial of dupilumab adjunctive therapy for prevention of asthma exacerbations in urban children and adolescents with T2-high exacerbation-prone asthma.
详细描述
Protocol CAUSE-01 PANDA is a multicenter, double-blind, placebo-controlled, randomized trial of dupilumab adjunctive therapy for the reduction of asthma exacerbations in urban children and adolescents 6 to 17 years with T2-high exacerbation-prone asthma. Approximately 240 participants will be randomized 2:1 to one of two study arms: 1) guidelines-based asthma treatment + dupilumab, or 2) guidelines-based asthma treatment + placebo. Study treatment will continue for 1 year with an additional 3 months of follow-up following completion of study treatment.
An initial Screening Visit will be followed by a 4-week run-in period. After the run-in, participants who continue to meet eligibility criteria will be randomized to one of the 2 treatment arms and receive their first injection. Over the next 2 weeks, participants will return to the clinic for 3 early treatment response visits. Participants will receive injections of dupilumab, or placebo administered subcutaneously every two weeks (Q2W), or every four weeks (Q4W), over 12 months. Each participant will have Evaluation and Management (E&M) visits every 3 months where their asthma and rhinitis will be assessed and adjustments made to their medications based on asthma guidelines.
Participants will be asked to monitor and self-report cold symptoms throughout the treatment period. Participants will be asked to complete up to three paired cold visits. At the time of a cold, participants will be asked to come into the clinic for collection of blood and nasal secretions for associated mechanistic studies. Approximately three days after the clinic visit, participants will complete symptom assessments and will be asked to collect nasal samples at home
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 6 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant and/or parent guardian must be able to understand and provide informed consent and age-appropriate assent
- •Are male and female aged 6-17 years at Visit 0
- •Participant has a primary place of residence in one of the pre-selected recruitment census tracts as outlined in the Protocol CAUSE01 Manual of Operations (MOP). Participants who do not live in the pre-selected census tracts but live within the Office of Management and Budget (OMB) defined Metropolitan Statistical Area and have publicly funded health insurance will qualify for inclusion.
- •Participant has a diagnosis of asthma made > 1 year prior to recruitment. Participants who received an asthma diagnosis by a clinician ≤1 year prior to recruitment must report that their respiratory symptoms were present for more than 1 year prior to recruitment.
- •Participant has had at least two asthma exacerbations in the prior year (defined as a requirement for systemic corticosteroids and/or hospitalization).
- •At Visit 0 (screening), participant must have the following requirement for asthma controller medication:
- •Participants aged 6 to 11 years: treatments with at least fluticasone 250 mcg dry powder inhaler (DPI) one puff twice daily or its equivalent.
- •Participants aged 12 years and older, treatment with at least fluticasone 250 mcg plus long-acting beta agonist (LABA) DPI one puff twice daily or its equivalent.
- •Have peripheral blood eosinophils ≥150 cells/mcl and/or FeNO ≥ 20ppb obtained at Visit 0 or via another CAUSE protocol within 6 months.
- •Are able to perform acceptable and repeatable spirometry per American Thoracic Society (ATS) criteria prior to randomization.
- •Have documentation of current medical insurance with prescription coverage at Visit 0.
排除标准
- •Parent or guardian is not able or willing to give written informed consent or comply with study protocol.
- •Have concurrent medical problems that would require systemic corticosteroids or other immunomodulators during the study.
- •Are currently receiving immunotherapy.
- •Are currently receiving treatment with a biologic therapy or have received a biologic therapy within 3 months prior to randomization.
- •Are currently requiring greater than fluticasone 500 mcg bid plus long-acting beta agonist (LABA) one puff twice daily or its equivalent plus Long-acting muscarinic antagonists (LAMA) and/or individuals using oral corticosteroids daily or every other day for more than 14 days at the time of Visit
- •Are currently pregnant or lactating, or plan to become pregnant during the time of study participation. Participants of child-bearing potential (post-menarche) must be abstinent or use a medically acceptable birth control method throughout the study (i.e., oral subcutaneous, mechanical, or surgical contraception). Males who are sexually active must agree to use an acceptable method of birth control (i.e., barrier methods with vaginal spermicide) or have a partner practicing an approved birth control method.
- •Have a known, pre-existing clinically important lung condition other than asthma.
- •Have a current malignancy or previous history of cancer in remission for less than 12 months prior to randomization.
- •Is a current smoker or is currently using any electronic cigarette or vaping device (e.g. e-cigarette, e- cig, mod, vape pen, JUUL, e-cigar, e-hookah, e-pipe, vape pods).
- •Have a known immunodeficiency disease.
- •Have a known, active pre-existing parasitic infection or are undergoing treatment for a parasitic infection. Once the participant has been successfully treated, the participant may be reevaluated.
- •Use of investigational drugs within 4 weeks of randomization
- •Have past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the site investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.
- •Will not allow the study clinician, an asthma specialist, to manage their disease for the duration of the study or who is not willing to change their asthma medications to follow the Protocol CAUSE- 01 PANDA.
- •Have a known history of allergic reaction to dupilumab.
- •Have had a life-threatening asthma exacerbation in the last 2 years requiring intubation, mechanical ventilation or resulting in a hypoxic seizure.
- •Have received a live (attenuated) vaccine within 4 weeks of Visit
- •Have an eosinophil count of ≥1500 cells/mcl at Visit
- •Potential participants may be reassessed as outlined in the Protocol CAUSE-01 MOP.
研究组 & 干预措施
Dupilumab
Participants between 12-17 years of age will receive an initial dose of 600 mg (two 300 mg injections) followed by 300 mg given every other week (Q2W).
Participants between 6-11 years of age will not complete a loading dose and will receive injections based on their body weight:
Those weighing 15 kg to less than 30 kg will receive 300 mg every four weeks (Q4W). Participants in this weight category who were randomized before July 1, 2024, were assigned to a 100mg Q2W and will not be transitioned to the Q4W dosing schedule.
Those with a body weight of 30 kg or more will receive 200 mg Q2W.
干预措施: Dupilumab (Drug)
Placebo
Participants between 12-17 years of age will receive an initial dose of placebo (two injections) followed by a placebo injection given every other week (Q2W).
Participants between 6-11 years of age will not receive an initial loading dose of placebo and will receive injections Q2W or Q4W based on their body weight and date of randomization.:
The injection volume of placebo will be matched to the corresponding dupilumab dose based on participant body weight.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of asthma exacerbations during the 12-month treatment period
时间窗: Week 4 (Treatment initiation) - Week 54 (Completion of treatment)
Asthma exacerbation defined as a prescription of a course of systemic steroids by a clinician or initiation of a course of systemic steroids by a participant to prevent a serious asthma outcome. If a participant initiates and completes a course of systemic steroids without clinician involvement, this course will be counted only if it meets the following dosage: the course for prednisone, prednisolone, or methylprednisolone will be at least 20 mg daily dose for 3 of 5 consecutive days. The course for dexamethasone will be at least a 10 mg single daily dose. If a corticosteroid burst for the treatment of an asthma exacerbation is prescribed by a non-CAUSE clinician, it will be counted regardless of dose.
次要结局
- Pulmonary Function Measured by Spirometry: Forced Expiratory Volume in 1 Second (FEV1) % Predicted(Week 4 to Week 68)
- Days with symptoms, nights with symptoms, and day and night albuterol use.(Week 4 to Week 68)
- Asthma control measured by the Asthma Control Questionnaire-5(Week 4 to Week 60)
- Time to first asthma exacerbation(Week 4 to Week 68)
- Quality of life as measured by the PROMIS Asthma Impact Short Forms (Pediatric or Parent Proxy).(Week 4 to Week 68)
- Asthma burden as measured by Combined Asthma Severity Index (CASI)(Week 4 to Week 68)
- Rhinitis symptoms as measured by Modified Rhinitis Symptoms Utility Index (MRSUI)(Week 4 - Week 68)
- Related adverse events and serious adverse events in the course of treatment(Week 4 to Week 68)