Topical rVA576 for Treatment of Atopic Keratoconjunctivitis: a Randomised Placebo-controlled Double Masked Parallel Trial (TRACKER)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 12
- 试验地点
- 9
- 主要终点
- Incidence of Ocular TEAE
研究概览
简要总结
Topical rVA576 for treatment of atopic keratoconjunctivitis (AKC), vernal keratoconjunctivitis (VKC),and severe allergic conjunctivitis (seasonal (SAC) or perennial (PAC)): a randomised placebo-controlled double masked parallel trial (TRACKER)
详细描述
Recombinant rVA576 is a small protein (16.7kDa) which has two independent actions. It inhibits the activation and cleavage of complement C5 and it binds and inactivates leukotriene B4 (LTB4). It acts on the complement system by preventing the cleavage of C5 by C5 convertase into C5a and C5b and so is effective in inhibiting terminal complement activity irrespective of the activating pathway.
Atopic keratoconjunctivitis (AKC) is a type of allergic conjunctivitis which involves mast cell activation due to the predominance of inflammatory mediators such as eosinophils and Th2-generated cytokines (Mishra et al. 2011).
Recombinant rVA576 eye drops solution is the investigational medicinal product. It is intended for ophthalmic use by topical administration to the eye.
Recombinant rVA576 is a compact small protein molecule with a lipocalin-like structure consisting of alpha helices and a beta barrel. There is a surface-active site which binds to the complement C5 molecule with a high affinity (KD 1.85 x 10-8 M) and an internalised active site which binds the small eicosinoid molecule leukotriene B4 (Hepburn et al. 2007).
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
- Double (Participant, Investigator)
盲法说明
Randomised, double-masked, placebo-controlled parallel group comparison with open-label sentinel group.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 18 and above
- •Diagnosis of moderate to severe AKC, VKC, or severe allergic conjunctivitis (seasonal or perennial). Defined as:
- •AKC, VKC - a composite symptom/sign score from one eye of ≥ 18 out of 33
- •Severe allergic conjunctivitis (SAC or PAC) - a composite symptom/sign score from one eye of ≥ 15 out of 27
- •Will have had received some topical therapy during the last 3 months without improvement but will not currently be receiving systemic immunotherapy. Topical therapy may be topical calcineurin inhibitors, antihistamines or corticosteroids alone or in combination. Lubricants or artificial tears will not a count as topical therapy for these purposes.
- •Will have had at least 7 days without topical ocular corticosteroids prior to entry
- •Willing to give informed consent
- •Willing to use highly effective contraceptive precautions for the duration of the study and for 90 days after the last dose of IMP
- •Willing to avoid prohibited medications for duration of study (see list of prohibited medications)
排除标准
- •Eye surface disease other than AKC, VKC or severe allergic conjunctivitis (SAC or PAC)
- •Contact lens use during the study
- •Complete or partial tarsorrhaphy. If such a procedure becomes necessary during the course of the trial patients may remain in the trial providing that at least 50% of the eye surface remains visible to slit lamp examination
- •Ankyloblepharon of any degree at entry to the trial
- •Known or suspected ocular malignancy
- •Active ocular infection at entry to the trial. Patients with eye surface bacterial, viral, fungal or protozoal infection may enter the trial after elimination of the infection as confirmed by eye swabs
- •Known or suspected uveitis
- •Participation in any other clinical trial within 1 month of enrolment
- •Use of any of the following prohibited medications:
- •Eculizumab
- •Any other investigational complement inhibitor whether systemic or topical (e.g. RA101495)
- •Montelukast
- •Zafirlukast
- •Pranlukast
- •Hypericum perforatum (St John's wort)
- •Corneal perforation
- •Uncontrolled glaucoma (increase in dose of glaucoma medication or surgical intervention for glaucoma within 3 months prior to entry)
- •Pregnancy (females)
- •Breast feeding (females)
- •Known allergy to ticks or severe reaction to arthropod venom (e.g. bee or wasp venom)
- •Use of topical ocular steroids within 7 days of the Screening visit
- •Failure to satisfy the PI of suitability to participate for any other reason
研究组 & 干预措施
rVA576 - Open-label period
Part 1: The first 3 patients selected for the study will be treated with the active drug in an open-label manner at intervals of 1 week and will have weekly clinic visits until Day 14, after which the visit will be every two weeks. When the first 3 patients have completed two weeks of treatment and the safety and tolerability data has been reviewed by the PI and an independent clinician, provided the data is favourable the randomisation process will begin (Part 2). The first 3 patients will continue treatment for a total of 8 weeks and will be assessed throughout the trial by the Principal Investigator according to the Schedule of Events
干预措施: rVA576 (Drug)
Placebo - Double-blind period
Part 2: Sixteen patients will be randomised 1:1. between active and placebo and patients allocated to either group will receive the appropriate product throughout the trial.
干预措施: Placebo (Other)
rVA576 - Double-blind period
Part 2: Sixteen patients will be randomised 1:1. between active and placebo and patients allocated to either group will receive the appropriate product throughout the trial.
干预措施: rVA576 (Drug)
结局指标
主要结局
Incidence of Ocular TEAE
时间窗: 56 days
Incidence of ocular treatment-emergent adverse events (TEAE) during the treatment period which have occurred during the 56 days following randomisation.
次要结局
- Post-instillation Comfort(Day 1 to 56)
- Visual Acuity(Day 1 to 56)
- Clinical Scores(Day 1 to 56)
- MMP-9 Positive(Day 1 to 56)
- Tear Film Break up Time(Change from Day 1 at Day 14, 28, 42 and 56)