Grass Pollen Sublingual Tablet Immunotherapy Plus Dupilumab for Induction of Tolerance in Adults With Moderate to Severe Seasonal Allergic Rhinitis (ITN084AD)
概览
- 阶段
- 2 期
- 干预措施
- Dupixent®
- 疾病 / 适应症
- Allergic Rhinoconjunctivitis
- 发起方
- National Institute of Allergy and Infectious Diseases (NIAID)
- 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
- 状态
- 已完成
- 最后更新
- 5天前
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.
研究者
入排标准
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),
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.
研究组 & 干预措施
Grazax® +Dupixent®
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®
Grazax® Placebo +Dupixent® Placebo
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
Grazax® +Dupixent®
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®
Grazax® + Dupixent® Placebo
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®
Grazax® + Dupixent® Placebo
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
Grazax® Placebo +Dupixent® Placebo
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
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)