NCT04502966已完成2 期
Grass Pollen Sublingual Tablet Immunotherapy Plus Dupilumab for Induction of Tolerance in Adults With Moderate to Severe Seasonal Allergic Rhinitis (ITN084AD)
National Institute of Allergy and Infectious Diseases (NIAID)2 个研究点 分布在 1 个国家目标入组 199 人开始时间: 2020年11月5日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 199
- 试验地点
- 2
- 主要终点
- TNSS Area Under Curve (AUC) Post Nasal Allergen Challenge (NAC) Over the First Hour After the Challenge (0-1 Hour (hr) at Year 3
研究概览
简要总结
The primary objective of this study is to assess whether the combination of grass allergen sublingual immunotherapy (SLIT) and dupilumab for 2 years is more effective than double placebo in suppressing the nasal allergen challenge (NAC) response to grass pollen at 1 year after completion of study medication.
详细描述
This is a double-blind (masked) placebo-controlled trial in adults (N=108 subjects will be enrolled) with moderate to severe seasonal allergic rhinitis and allergic sensitization to grass pollen. Eligible participants who demonstrate a positive response defined by a Total Nasal Symptom Score [TNSS] ≥ 5 (Scale 0-12 in response to a Nasal Allergen Challenge [NAC] with grass pollen extract), will be randomized to one of the following 3 groups in a 1:1:1 ratio:
- Grass allergen sublingual immunotherapy (SLIT) + dupilumab (n=36)
- Grass allergen SLIT +dupilumab placebo (n=36)
- Grass allergen SLIT placebo + dupilumab placebo (n=36)
Grazax® is a sublingual grass allergen immunotherapy product approved for clinical use in the United Kingdom and will be used as SLIT in this study. Grazax (and its matching placebo) will be self-administered daily by participants for a duration of two years.
Dupixent®is the brand name for dupilumab and is a monoclonal antibody against the interleukin 4 (IL-4) receptor. Dupilumab (and its matching placebo) will be administered every two weeks by subcutaneous injection through for a duration of two years, administered by study personnel. The treatment phase of two years will be followed by an observation phase of 1 year.
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
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant must be able to understand and provide informed consent
- •A clinical history of grass pollen-induced allergic rhinoconjunctivitis for at least 2 years, with peak symptoms in May, June, or July
- •A clinical history of moderate to severe rhinoconjunctivitis symptoms for at least 2 years, interfering with usual daily activities or with sleep as defined according to the Allergic Rhinitis and Its Impact on Asthma (ARIA) classification of rhinitis
- •A clinical history of inadequately controlled rhinoconjunctivitis symptoms, despite treatment with antihistamines and/or nasal corticosteroids during the grass pollen season, for at least 2 years
- •Positive skin prick test response at screening, defined as wheal diameter ≥3 mm to Phleum pratense
- •Positive specific immunoglobulin E (IgE) at screening, defined as IgE class 2 (e.g., ≥ 0.7 kilounits per liter [kU/L]) against Phleum pratense
- •A woman of childbearing potential (WOCBP), regardless of birth control history, must:
- •have a negative serum pregnancy test at screening,
- •not be breast-feeding or lactating, and ---is required to consistently use one of the following highly effective methods of contraception throughout the study:
- •hormonal (e.g. oral, transdermal, intravaginal, implant, or injection),
- •intrauterine device (IUD) or system (IUS),
- •vasectomized partner,
- •bilateral tubal occlusion, or
- •sexual abstinence.
排除标准
- •Inability or unwillingness of the Subject to give written informed consent or to comply with study protocol requirements
- •Prebronchodilator forced expiratory volume (FEV1) <70% of predicted value at either Screening Visit or Baseline (Visit 0) Visit
- •A clinical history of asthma requiring regular inhaled corticosteroids for >4 weeks per year, outside of the grass pollen season
- •A clinical history of moderate to severe allergic rhinitis, as defined according to the Allergic Rhinitis and Its Impact on Asthma (ARIA) classification of rhinitis, caused by either:
- •An allergen to which the Subject is regularly exposed, or
- •Tree pollen during tree pollen season, treated with regular antihistamine or intranasal corticosteroids
- •History of emergency visit or hospital admission for asthma in the previous 12 months
- •History of chronic obstructive pulmonary disease
- •History of recurrent acute sinusitis, defined as 2 episodes per year for the last 2 years, all of which required antibiotic treatment
- •History of chronic sinusitis, defined as a sinus symptoms lasting greater than 12 weeks, that includes 2 or more major factors or 1 major factor and 2 minor factors.
- •Major factors are defined as:
- •Facial pain or pressure,
- •Nasal obstruction or blockage,
- •Nasal discharge or purulence or discolored postnasal discharge,
- •Purulence in nasal cavity, or
- •Impaired or loss of smell.
- •Minor factors are defined as:
- •Headache,
- •Halitosis,
- •Dental pain,
- •Cough, and/or
- •Ear pain, pressure, or fullness.
- •History of systemic disease affecting the immune system, such as autoimmune diseases, immune complex disease or immunodeficiency
- •At randomization: Current symptoms of, or treatment for:
- •Upper respiratory tract infection,
- •Acute sinusitis,
- •Acute otitis media, or
- •Other relevant infectious process ---Note: 1.) Serous otitis media is not an exclusion criterion and 2.) Participants may be re-evaluated for eligibility after symptoms resolve.
- •A past history of any malignant disease in the previous 5 years
- •Any tobacco smoking within the last 6 months, or a history of greater than or equal to 10 pack years of cigarette use.
- •Any vaping or electronic cigarette use within the last 6 months
- •Previous immunotherapy with grass pollen allergen within the previous 5 years
- •Previous treatment by dupilumab (Dupixent®)
- •Previous Grade 4 anaphylaxis (World Allergy Organization grading criteria), due to any cause
- •History of anti-IgE, anti-IL-5, anti-IL-5 receptor, anti-IL-4/IL-13 receptor, or other monoclonal antibody treatment
- •Use of tricyclic antidepressants or monoamine oxidase inhibitors
- •Ongoing systemic immunosuppressive treatment
- •History of intolerance to the study therapy, rescue medications, or their excipients
- •For women of childbearing age a positive serum or urine pregnancy test with sensitivity of less than 50 milli-international units per milliliter [mIU/ml] within 72 hours before the scheduled start of study therapy
- •The use of any investigational drug within 30 days of the Screening Visit
- •The presence of any medical condition that the investigator deems incompatible with participation in the trial
- •Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or may impact the quality or interpretation of the data obtained from the study
- •Eosinophilic esophagitis or a diagnosis of any hypereosinophilic syndrome, and/or
- •Administration of live attenuated vaccines within four weeks of dupilumab or dupilumab placebo injections, before the first injection and throughout the treatment period.
研究组 & 干预措施
Grazax® +Dupixent®
Experimental
Participants randomized to this assignment will receive the following during the initial 2-year period of the trial:
- Once daily tablet of Grazax® sublingual immunotherapy and
- Dupixent® administered every other week (e.g., biweekly) by subcutaneous injection
干预措施: Dupixent® (Biological)
Grazax® Placebo +Dupixent® Placebo
Placebo Comparator
Participants randomized to this assignment will receive the following during the initial 2-year period of the trial:
- Once daily tablet of placebo for Grazax® sublingual immunotherapy and
- Placebo for Dupixent® administered every other week (e.g., biweekly) by subcutaneous injection
干预措施: Dupixent® Placebo (Drug)
Grazax® +Dupixent®
Experimental
Participants randomized to this assignment will receive the following during the initial 2-year period of the trial:
- Once daily tablet of Grazax® sublingual immunotherapy and
- Dupixent® administered every other week (e.g., biweekly) by subcutaneous injection
干预措施: Grazax® (Biological)
Grazax® + Dupixent® Placebo
Experimental
Participants randomized to this assignment will receive the following during the initial 2-year period of the trial:
- Once daily tablet of Grazax® sublingual immunotherapy and
- Placebo for Dupixent® administered every other week (e.g., biweekly) by subcutaneous injection
干预措施: Grazax® (Biological)
Grazax® + Dupixent® Placebo
Experimental
Participants randomized to this assignment will receive the following during the initial 2-year period of the trial:
- Once daily tablet of Grazax® sublingual immunotherapy and
- Placebo for Dupixent® administered every other week (e.g., biweekly) by subcutaneous injection
干预措施: Dupixent® Placebo (Drug)
Grazax® Placebo +Dupixent® Placebo
Placebo Comparator
Participants randomized to this assignment will receive the following during the initial 2-year period of the trial:
- Once daily tablet of placebo for Grazax® sublingual immunotherapy and
- Placebo for Dupixent® administered every other week (e.g., biweekly) by subcutaneous injection
干预措施: Grazax® Placebo (Drug)
结局指标
主要结局
TNSS Area Under Curve (AUC) Post Nasal Allergen Challenge (NAC) Over the First Hour After the Challenge (0-1 Hour (hr) at Year 3
时间窗: 0 to 1 hour of the NAC at Year 3 (One Year After Completion of Treatment)
NAC (TNSS Area-under-Curve \[AUC 0-1hr\]), comparing the TNSS AUC 0-1 hr between the referenced treatment arms: a clinical tolerance outcome measure at Year 3, one year after completion of treatment. The Total Nasal Symptom Score (TNSS) is a participant-reported composite symptom assessment of 4 symptoms (rhinorrhea, nasal congestion, nasal itching and sneezing), each scored on a scale from 0 to 3 where 0 = none, 3 = severe. TNSS total score is calculated as the sum of the response for all 4 individual nasal symptom scores and can range from a minimum score of 0 to a maximum score of 12: a higher score indicates more severe symptoms. The primary treatment comparison is between SLIT/Dupilumab and Double-Placebo.
次要结局
- TNSS Area Under Curve (AUC) Post Nasal Allergen Challenge (NAC) Over the First Hour After the Challenge (0-1 Hour (hr) at Years 1 and 2(0 to 1 hour of the NAC at Years 1 and 2)
- Peak Nasal Inspiratory Flow (PNIF) (Delta PNIF Area Under the Curve [AUC] 0-1 hr) at Years 1, 2, and 3(0 to 1 hour of the NAC at Years 1 and Year 2, and at Year 3 (One Year After Completion of Treatment))
- TNSS Peak (Maximum) Value Post Nasal Allergen Challenge (NAC) Over the First Hour After the Challenge (0-1 Hour (hr) at Years 1, 2, and 3(0 to 1 hour of the NAC at Years 1 and Year 2, and at Year 3 (One Year After Completion of Treatment))
- Size of Early Intradermal Skin Test Response at Years 1, 2, and 3(Years 1 and Year 2, and at Year 3 (One Year After Completion of Treatment))
- Size of Late Intradermal Skin Test Response at Years 1, 2, and 3(Years 1 and Year 2, and at Year 3 (One Year After Completion of Treatment))
- Modified Rhinitis Symptom Utility Index (MRSUI) Questionnaire Measured In-Season at Years 1, 2, and 3(Years 1 and Year 2, and at Year 3 (One Year After Completion of Treatment))
- Global Evaluation Questionnaire Number 1 at Years 1, 2, and 3(Years 1 and Year 2, and at Year 3 (One Year After Completion of Treatment))
- Global Evaluation Questionnaire Number 2 at Years 1, 2, and 3(Years 1 and Year 2, and at Year 3 (One Year After Completion of Treatment))
- Frequency, Severity, and Relatedness of Treatment-Emergent Adverse Events (AEs) by Treatment Arm(Start of study treatment until completion of study participation at year 3, or until 30 days after prematurely withdrawing from the study)
- Size of Skin Prick Test Endpoint Titration Response as Defined by the Provocative Concentration at 5mm (PC5) at Years 1, 2, and 3(Years 1 and Year 2, and at Year 3 (One Year After Completion of Treatment))
- Weekly Seasonal Combined Symptom Medication Score (CSMS) at Years 1, 2, and 3 (In Season Estimates)(Years 1 and Year 2, and at Year 3 (One Year After Completion of Treatment))
- Weekly Seasonal Visual Analogue Scale (VAS) 0-10cm Score at Years 1, 2, and 3 (In Season Estimates)(Years 1 and Year 2, and at Year 3 (One Year After Completion of Treatment))
- Weekly Seasonal Medication Score (WMS) at Years 1, 2, and 3 (In Season Estimates)(Years 1 and Year 2, and at Year 3 (One Year After Completion of Treatment))
- Weekly Rhinitis Quality of Life Score Using the Juniper Mini-Rhinoconjunctivitis Quality of Life Questionnaire (miniRQLQ) at Years 1, 2, and 3 (In Season Estimates)(Years 1 and Year 2, and at Year 3 (One Year After Completion of Treatment))
- TNSS Area Under Curve (AUC) Post Nasal Allergen Challenge (NAC) Over the First Hour After the Challenge (0-1 Hour (hr) at Years 1 and 2(0 to 1 hour of the NAC at Years 1 and 2)
- Peak Nasal Inspiratory Flow (PNIF) (Delta PNIF Area Under the Curve [AUC] 0-1 hr) at Years 1, 2, and 3(0 to 1 hour of the NAC at Years 1 and Year 2, and at Year 3 (One Year After Completion of Treatment))
- TNSS Peak (Maximum) Value Post Nasal Allergen Challenge (NAC) Over the First Hour After the Challenge (0-1 Hour (hr) at Years 1, 2, and 3(0 to 1 hour of the NAC at Years 1 and Year 2, and at Year 3 (One Year After Completion of Treatment))
- Size of Early Intradermal Skin Test Response at Years 1, 2, and 3(Years 1 and Year 2, and at Year 3 (One Year After Completion of Treatment))
- Size of Late Intradermal Skin Test Response at Years 1, 2, and 3(Years 1 and Year 2, and at Year 3 (One Year After Completion of Treatment))
- Size of Skin Prick Test Endpoint Titration Response as defined by the Provocative Concentration at 5mm (PC5) at Years 1, 2, and 3(Years 1 and Year 2, and at Year 3 (One Year After Completion of Treatment))
- Weekly Seasonal Combined Symptom Medication Score (CSMS) at Years 1, 2, and 3(Years 1 and Year 2, and at Year 3 (One Year After Completion of Treatment))
- Weekly Seasonal Visual Analogue Scale (VAS) 0-10 cms Score at Years 1, 2, and 3(Years 1 and Year 2, and at Year 3 (One Year After Completion of Treatment))
- Weekly Seasonal Medication Score (WMS) at Years 1, 2, and 3(Years 1 and Year 2, and at Year 3 (One Year After Completion of Treatment))
- Weekly Rhinitis Quality of Life Score Using the Juniper Mini-Rhinoconjunctivitis Quality of Life Questionnaire (miniRQLQ) at Years 1, 2, and 3(Years 1 and Year 2, and at Year 3 (One Year After Completion of Treatment))
- Modified Rhinitis Symptom Utility Index (MRSUI) Questionnaire Measured In-Season at Years 1, 2, and 3(Years 1 and Year 2, and at Year 3 (One Year After Completion of Treatment))
- Global Evaluation Questionnaire Number 1 at Years 1, 2, and 3(Years 1 and Year 2, and at Year 3 (One Year After Completion of Treatment))
- Global Evaluation Questionnaire Number 2 at Years 1, 2, and 3(Years 1 and Year 2, and at Year 3 (One Year After Completion of Treatment))
- Frequency, Severity, and Relatedness of Treatment-Emergent Adverse Events (AEs) by Treatment Arm(Start of study treatment until completion of study participation at year 3, or until 30 days after prematurely withdrawing from the study)
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研究点 (2)
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