Clinical Evaluation of Two Different Dosage Groups of Tacrosolv Eye Drops in a Placebo Controlled Crossover Design to Evaluate Safety and Efficacy in Patients Suffering From Grass Pollen Induced Allergic Rhinoconjunctivitis in the Vienna Challenge Chamber.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- Total Ocular Symptom Score
研究概览
简要总结
Allergic conjunctivitis is one of the most common comorbidities of allergic diseases, especially of allergic rhinitis.
Rhinoconjunctivitis is an allergic condition of the nasal mucosa and the eyes. Conjunctivitis is triggered by hypersensitivity to certain pollens and other airborne allergens and causes several symptoms such as reddened eyes, itchy eyes and can cause watery eyes and a scratchy feeling in the eye. Tacrolimus is a well-known immunosuppressiv active substance which is hardly soluble in water. Within Tacrosolv, Tacrolimus is completely dissolves in aqueous solution. The effectiveness of Tacrosolv will be tested for treatment of allergic conjunctivitis. Allergic subjects will be treated with aqueous formulation of tacrolimus 'Tacrosolv 50 micrograms per milliliter, eye drops' for 8 days. On day 1 and day 8 allergic patients will be challenged with grass pollen for a period of 4 hours and subjective allergic symptoms will be assessed.
详细描述
This is a randomized, placebo controlled, crossover, double-blind, single site trial in adult subjects (18-65 years of age) who have demonstrated grass specific Immunglobulin E (IgE) reactivity and have a history of grass pollen induced rhinoconjunctivitis with or without controlled asthma. The crossover design will ensure that individual subjects will receive either one drop Tacrosolv compared to two drops placebo or 2 drops Tacrosolv compared to 1 drop placebo.
The primary objective of the trial is to demonstrate the safety and efficacy of two doses of Tacrosolv on day 8 of treatment. To assure full blinding, two study populations are treated in a crossover design against placebo.
The evaluation will be based on the assessment of ocular symptoms during grass pollen challenge performed in the Vienna Challenge Chamber (environmental exposure chamber).
Secondary objective of the trial is to evaluate the onset of action of either dose of Tacrosolv on day one of treatment as well as efficacy differences between low dose and high dose treatment on day eight.
Visit 1 - Screening:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •A subject will be eligible for inclusion in this study only if all of the following criteria apply:
- •Written informed consent obtained before any trial related procedures are performed
- •Healthy male or female subjects aged 18 to 65 years
- •Female subjects of child-bearing potential must have a negative pregnancy test and be willing to practice appropriate and safe contraceptive methods until the end of treatment visit
- •A documented clinically relevant allergic history of moderate to severe SAR with rhinoconjunctivitis to grass pollen for the previous two years
- •Subjects exhibit a moderate to severe response to approximately 1800 grass pollen grains/m3 within the first 2 hours in the Vienna Challenge Chamber, which is defined as total ocular symptom score (TOSS) of at least 4 (out of 12) with at least one single ocular symptom scored ≥2 ("moderate") at least twice during the first two hours of the screening challenge session using standard VCC grass pollen allergen mixture. Ocular symptom score is the sum of "ocular redness", "ocular itching", "watery eyes", "gritty feeling" each of which have been scored on a categorical scale from 0 to
- •Positive Skin Prick Test (SPT) response (wheal diameter at least 3 mm larger than diluent control) to grass pollen SPT solutions (standard Allergopharma) at screening or within the last 12 months prior to study start.
- •Positive serum specific IgE against recombinant major allergen components of the used grass pollen e.g. g6 (specific CAP IgE ≥0.70 kU/L) at screening or within the last 12 months prior to study start.
- •Non-smoking subjects (smoked <10 packs per year in their lifetime and had not smoked in the last 6 months).
- •Asthma patients only if the asthma condition is mild or intermittent, and if those are not treated with steroids
- •Subject has a forced expiratory volume in 1 second (FEV1) of at least 80% of predicted value (ECCS) at the screening.
- •Subject is capable of understanding the study procedures and potential risks associated with the study, and voluntarily agrees to participate by giving written informed consent.
- •Subject is able to adhere to dose and visit schedules.
- •Subject is able to read, understand and complete questionnaires and diaries.
排除标准
- •A subject meeting any of the exclusion criteria listed below must be excluded from participating in the trial:
- •Pregnant, lactating or sexually active women with childbearing potential who are not using a medically accepted and safe birth control method (pregnancy to be controlled by a pregnancy dipstick test).
- •Contact lens users
- •A clinical history of uncontrolled asthma within 3 months prior to screening.
- •Subjects with asthma requiring treatment with inhaled or oral corticosteroids on a regular basis judged by the investigator
- •Previous successful immunotherapy to grass pollen, a grass pollen allergen or a cross-reacting allergen within the past 3 years
- •Ongoing treatment with any allergen-specific immunotherapy product
- •Subjects with a current oral candidiasis infection or treatment for oral candidiasis during the last 30 days before starting the study.
- •Subjects with history of tuberculosis.
- •Subjects with any fungal/viral/bacterial respiratory or systemic infections during the last 30 days.
- •Symptoms of or treatment for upper respiratory tract infection, acute sinusitis, acute otitis media or other relevant infectious process (at randomization)
- •Subjects with uveitis, prior chemical burn to the ocular surface, pemphigoid, Mooren's ulcer, ulcerative keratitis, bacterial/fungal/viral infection of the eye
- •Subjects using any ophthalmic steroids during the last 30 days
- •Subjects treated with nasal, inhaled or systemic immunosuppressants during the last 30 days
- •History of anaphylaxis with cardiorespiratory symptoms (immunotherapy, exercise induced, food allergy, drugs or an idiopathic reaction).
- •Any clinically relevant chronic disease judged by the investigator.
- •Systemic or ocular disease involving the immune system judged by the investigator.
- •Use of an investigational drug within 30 days/5 half-lives of the drug (which ever longest) prior to screening.
- •History of allergy, hypersensitivity or intolerance to any ingredients of the IMP.
- •History of alcohol or drug abuse
- •Being immediate family of the investigator or trial staff, defined as the investigator's/staff's spouse, parent, child, grandparent or grandchild.
- •Subjects treated with topical anti-allergy or cyclosporin-containing eyedrops within 2 weeks before study start
- •Subjects treated with leukotriene antagonists (1 month before study start), long- lasting anti-histamines, like cetirizine, fexofenadine, loratadine, desloratadine, hydroxyzine (5 to 10 days before study start), mast cell stabilizer (2 weeks before study start) or nasal decongestant (3 days before study start)
- •Subjects with hypersensitivity to immunosuppressants judged by the investigator.
- •Presence or history of any ocular infection or clinically significant inflammation
- •Ocular surgery in the 3 months preceding the study
- •Treatment with corticosteroids in the 4 weeks preceding the study
- •Is currently being treated with a medication that induces or inhibits CYP3A4 or 5
研究组 & 干预措施
Placebo low dose
Application of 2 placebo eye drops once daily for 8 days.
干预措施: Eye Drops, Solution in Single-Dose Container (Drug)
Tacrosolv low dose
Application of 1 Tacrosolv eye drop once daily for 8 days.
干预措施: Eye Drops, Solution in Single-Dose Container (Drug)
Placebo high dose
Application of 1 placebo eye drop once daily for 8 days.
干预措施: Eye Drops, Solution in Single-Dose Container (Drug)
Tacrosolv high dose
Application of 2 Tacrosolv eye drops once daily for 8 days.
干预措施: Eye Drops, Solution in Single-Dose Container (Drug)
结局指标
主要结局
Total Ocular Symptom Score
时间窗: 0-4 hours of allergen challenge
The total ocular symptom score is the sum of four eye symptoms 'red eyes', 'itchy eyes', and 'watery eyes' and 'gritty feeling' scored every 15 minutes on a categorical scale from 0 (none) to 3 (severe) on challenge day at the times described in the Time and Events Schedule
次要结局
- Total respiratory symptom score (TRSS)(0-4 hours of allergen challenge)
- Nasal airflow (AAR)(0-4 hours of allergen challenge)
- Total nasal symptom score (TNSS)(0-4 hours of allergen challenge)
- change in ocular redness image score(0-4 hours of allergen challenge)