Prospective, Randomised, DBPC Clinical Trial to Evaluate the Efficacy and Safety of Polymerized and Mannan Conjugated Allergen Extract of Dermatophagoides for the Treatment of Allergic Rhinitis/Rhinoconjunctivitis With or Without Asthma
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 90
- 试验地点
- 2
- 主要终点
- Rhinitis/rhinoconjunctivitis Combined Symptom and Medication Score (RCSMS)
研究概览
简要总结
Prospective, randomised, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of polymerized and mannan conjugated allergen extract of Dermatophagoides for the treatment of allergic rhinitis/rhinoconjunctivitis with or without asthma.
The main objective of the clinical trial is to evaluate the clinical efficacy of the investigational medicinal product, administered sublingually, compared to placebo for the treatment of moderate-severe rhinitis/rhinoconjunctivitis with or without mild to moderate asthma and controlled using the Rhinitis/Rhinoconjunctivitis Combined Symptom and Medication Score (R-CSMS).
详细描述
Allergen-specific immunotherapy (AIT) has been shown to be effective in relieving symptoms, reducing medication use, and improving quality of life in patients with respiratory allergies). This is thought to be due to the induction of a state of tolerance to specific allergens with long-lasting effects after discontinuation of treatment. And it is accepted that immunotherapy is the only available method for allergists to improve or cure, partially or definitely, an allergic process The study population of this clinical trial will comprise subjects allergic to mites (Dermatophagoides pteronyssinus and/or D. farinae) with symptoms of moderate-severe rhinitis/rhinoconjunctivitis with or without mild to severe controlled asthma, suitable to allergen immunotherapy.
The primary efficacy endpoint will be the combined rhinitis/rhinoconjunctivitis symptom and medication score.
Every single day from the beginning of the administration of the investigational drug (V2-VF), the subject will be asked to score and register his/her symptoms and record medication consumption in an electronic diary following the instructions of the application. This diary will provide the symptom score and medication consumption for each subject during the trial.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
During the trial, both the investigator and the subjects included will be unaware of the treatment each subject is receiving.
Blinding is intended to minimize potential biases resulting from differences in treatment or assessment of subjects. It is also intended to reduce as much as possible the interpretation of the results that could arise as a consequence of the investigator or the subject knowing the assigned treatment.
The person in charge of data analysis will also not know the treatment assigned to each subject until the database has been closed.
So that neither the subject nor the investigator will know which treatment each subject is receiving, all trial medication will be identical in outer packaging and appearance.
入排标准
- 年龄范围
- 12 Years 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed Informed Consent Form.
- •Male or female, aged between 12 and 60 years, both included.
- •Confirmed clinical history of inhalation allergy with moderate-severe rhinitis/rhinoconjunctivitis according to the ARIA classification with or without controlled mild-moderate intermittent or persistent asthma according to the definition of GEMA 5.0 y GINA caused by allergy to mites (D. pteronyssinus and/or D. farinae). The asthma diagnostic will be valid up to 24 months prior to signing the informed consent form.
- •Combined Symptom and Medication Score for moderate to severe rhinitis/rhinoconjunctivitis (RCSMS) ≥ 1,8 out of
- •Positive skin prick test (wheal major diameter ≥ 5 mm) to a standardized allergen extract of Dermatophagoides pteronyssinus and/or Dermatophagoides farinae. The results will be valid up to 12 months prior to signing the informed consent form.
- •Specific IgE against a complete extract of Dermatophagoides pteronyssinus and/or D. farinae or any the molecular components of allergenic sources with a value ≥ 3.5 kU/L. The results will be valid up to 12 months prior to signing the informed consent form.
- •Subjects shall preferably be monosensitised to the study allergens. In case of subjects sensitised to other aeroallergens, only those with the following characteristics may be included in the study (results will be valid up to 12 months prior to signing the informed consent form):
- •Subjects with a positive skin prick test to Blomia tropicalis and Lepidoglyphus destructor, whose wheal major diameter and specific IgE values do not exceed or equal the values for the study allergens.
- •Subjects with a positive skin prick test for dander if they have occasional exposure and symptoms.
- •Subjects with positive skin prick test to pollens, whose specific IgE values do not exceed or equal the values for the study allergens and who also do not have exacerbations during pollen season. The maximum specific IgE value to theses allergens is 17.5 kU/L.
- •Subjects with negative skin prick test to mold. In case specific IgE determination have been performed, the result must be <0.35 kU/L.
- •Women of childbearing age (since menarche) must present a negative urine pregnancy test at the time of trial enrollment.
- •Women of childbearing age must commit to using and adequate contraception method.
- •Subjects capable of complying with a dosage regimen.
- •Subjects owning a smartphone to register symptoms and medication consumption.
排除标准
- •Subjects polysensitized to other aeroallergens with clinically relevant symptoms.
- •Subjects who have received previous immunotherapy in the preceding 5 years to any of the tested allergens or a cross-reactive allergen or are currently receiving immunotherapy with any allergen.
- •Patients in whom immunotherapy may be subject to an absolute general contraindication according to the criteria of the Immunotherapy Committee of the Spanish Society of Allergy and Clinical Immunology and the European Allergy and Clinical Immunology Immunotherapy Subcommittee may not be included.
- •Subjects with uncontrolled severe asthma, and/or with FEV1 <80% of baseline despite adequate pharmacological treatment by the time of the enrolment.
- •Subjects on treatment with ß-blockers.
- •Subjects on treatment with immunosuppressive or biological drugs.
- •Subjects who are unstable by the time of enrolment (respiratory infection, febrile process, acute pruritus, etc.).
- •Subjects with chronic urticaria during the last 2 years, severe anaphylaxis or with hereditary angioedema history.
- •Subjects with any pathology in which the administration of adrenaline is contraindicating (hyperthyroidism, hypertension, heart disease, etc.) according to the investigator discretion.
- •Subjects with any other disease not related to moderate rhinoconjunctivitis or asthma, but potentially serious and that could interfere with treatment and follow-up (epilepsy, psychomotor disorders, diabetes, malformations, multi-surgery, nephropathy, etc.), according to the investigator discretion.
- •Subjects with severe autoimmune disease (thyroiditis, lupus, etc.), tumour diseases or diagnosed with immunodeficiencies.
- •Subject whose condition prevents him/her from offering cooperation and/or who presents severe psychiatric disorders, according to the investigator discretion.
- •Subjects with known allergy to the other components of the investigational product other than allergen study.
- •Subjects with lower airway diseases other than asthma such as emphysema or bronchiectasis.
- •Pregnant or breastfeeding women.
- •Subjects who are immediate family members of researchers.
- •Concurrent participation in other clinical trials or previous participation within 30 days prior to inclusion.
- •History of severe systemic reactions, including food, hymenoptera venom, etc.
- •Subjects who have suffered a respiratory tract infection and/or asthma exacerbation within 4 weeks prior to screening.
- •Subjects with a history of significant renal disease or chronic liver disease.
结局指标
主要结局
Rhinitis/rhinoconjunctivitis Combined Symptom and Medication Score (RCSMS)
时间窗: 6 months
Assessment of the number of rhinitis/rhinoconjunctivitis symptoms and medication consumption required to control these symptoms for each subject during the trial, for each group compared to the others, and compared to placebo. Rhinitis/Rhinoconjunctivitis Combined Symptom and Medication Score will be based on the work done by Pfaar et al. The score for each rhinitis/rhinoconjunctivitis symptom will be 0 = No symptoms; 1 = Mild; 2 = Moderate; 3 = Severe. Total daily symptom score = 0-3 The score for Rhinitis/rhinoconjunctivitis medication will be: 0 = No medication; 1 = Oral or topical (eye or nose) non-sedating H1 antihistamines (H1A); 2 = Intranasal corticosteroids (INS) with/without H1A; 3 = Oral corticosteroids with/without (INS), with/without H1A. Total daily medication score = 0-3
次要结局
- Medication free days (rhinitis/rhinoconjunctivitis, asthma)(6 months)
- Visual Analogue Scales (VAS)(7 months)
- Asthma Symptom Score (ASS)(6 months)
- Asthma exacerbations(4 months)
- Immunological parameters in blood(6 months)
- Security parameters(Month 2 and month 7)
- Rhinitis/ Rhinoconjunctivitis Symptom Score (RSS)(6 months)
- Rhinitis/Rhinoconjunctivitis Medication Score (RMS)(6 months)
- Asthma Combined Symptom and Medication Score (ACSMS)(6 months)
- Immunological parameters in nasal mucosa.(Month 2 and month 7)
- Asthma Control Questionnaire (ACQ 6)(4 months)
- Number of Local Adverse Reactions(6 months)
- Asthma and Rhinitis/Rhinoconjunctivitis Symptom Score (ARSS)(6 months)
- Symptom free-days (rhinitis/rhinoconjunctivitis, asthma)(6 months)
- Asthma Medication Score (AMS)(6 months)
- Asthma and Rhinitis/Rhinoconjunctivitis Medication Score (ARMS)(6 months)
- Asthma and Rhinitis/Rhinoconjunctivitis Combined Symptom and Medication Score (ARCSMS)(6 months)
- Clinical benefit(6 months)
- Number of eosinophil(6 months)
- Respiratory function(6 months)
- Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)(6 months)
- Asthma Control Questionnaire (ACQ 7)(6 months)
- Consumption of health resources(7 months)
- Asthma Quality of Life Questionnaire (AQLQ)(Month 2 and month 7)
- Number of Adverse Reactions to any medication(7 months)
- Number of Systemic Adverse Reactions(6 months)
- Compliance of the electronic diary(6 months)
- Treatment adherence(6 months)