A Historically Controlled Phase II/III Study to Evaluate Efficacy and Safety of Kedrion Human Plasminogen Eye Drop Preparation in Patients Diagnosed With Ligneous Conjunctivitis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 12
- 试验地点
- 4
- 主要终点
- Percentage of Success to Prevent Pseudomembranes Relapse
研究概览
简要总结
Kedrion Human Plasminogen, a sterile human plasma-derived plasminogen preparation for topical ocular use will be evaluated for the indication of treatment of ligneous conjunctivitis.
KB046 will be an open-label, historically controlled clinical trial. At least 10 subjects with ligneous conjunctivitis, for approximately 20 eyes, will be treated and assessed. All subjects will receive the investigational medicinal product (IMP) for 12 to 48 weeks, with a possibility for extended treatment (Continuation segment)
详细描述
Kedrion Human Plasminogen, a sterile human plasma-derived plasminogen preparation for topical ocular use will be evaluated for the indication of treatment of ligneous conjunctivitis.
KB046 will be an open-label, historically controlled clinical trial. At least 10 subjects with ligneous conjunctivitis, for approximately 20 eyes, will be treated and assessed. All subjects will receive the investigational medicinal product (IMP) for 12 to 48 weeks, with a possibility for extended treatment (Continuation segment).
The study will be divided into 3 segments: segments 1 and 2 for assessment of efficacy and safety and segment 3 (continuation segment) assessing long-term safety. For each enrolled patient, both eyes will be treated regardless of unilateral or bilateral involvement. Treatment of the unaffected eyes provided data for the safety assessment. To assess efficacy, comparisons will be made against individual patient historical data.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects should be diagnosed with ligneous conjunctivitis associated with Type I plasminogen deficiency, confirmed by the central laboratory and documented at pre-enrollment screening. The concomitant presence of other ligneous pseudomembranes at different sites will not constitute an exclusion criterion.
- •Subjects should have documented historical records of disease course available for a period of at least 6 months surrounding an episode of LC, even if asymptomatic in the past for a newly diagnosed subject , including but not limited to age of LC onset, diagnosis of Plasminogen 1 deficiency, history of pseudomembrane lesions, disease duration, past treatment for LC, response to treatment and/or surgery (including regression and recurrence), before study entrance. If more history than 6 months surrounding an LC episode is available it will be included.
- •Subjects, or their legally authorized representative, in the case of study participants < 18 years of age, should have been informed of the nature of the study, agreed to its provision, signed and dated the informed consent approved by the investigational review board (IRB) or ethics committee (EC).
- •Subjects available for the duration of the study will be included. The Investigator will make sure that there is no plan for the subject to leave the area of the study site before the end of the study period. If they come from another center, they must agree to be compliant with the protocol mandated study visits and return for follow-up.
排除标准
- •Subjects presenting ligneous conjunctivitis not associated with Type 1 plasminogen deficiency.
- •Subjects with no history of LC lesions for Group 2, for Group 1 the entry lesions could be the first and included as history.
- •Subject presenting antibodies against plasminogen at screening.
- •Subjects with any condition which, in the opinion of the Investigator, might interfere with the evaluation of the study objectives, or participation in this trial.
- •Subjects unwilling to give written informed consent or assent to participation.
- •Subjects who have participated in another clinical trial within 1 month before study initiation, i.e. they have received any test drug within 30 days prior the study.
- •Females of childbearing potential who are either pregnant or not using an adequate method of birth control
- •Females who are breastfeeding.
- •Subjects being treated with FFP or Laboratory Grade Plasminogen will undergo a washout period of at least 15 days before being considered for this study. This information will be disseminated to subjects ahead of their Screening Visit and will only occur following signing of the Informed Consent
结局指标
主要结局
Percentage of Success to Prevent Pseudomembranes Relapse
时间窗: The prevention of pseudomembranes relapse was assessed during Segment 2, after initial total regression at the end of Segment 1 (Group 1A) or after surgical excision (Group 1B) up to 21 weeks from the study start.
The primary endpoint (prevention of pseudomembrane relapse) was presented descriptively based on the predefined success levels: complete success (defined as no relapse by the end of Segment 2), partial success(defined as relapse appearing 2 weeks or longer after the start of Segment 2, or if following the 3 rd cycle of Segment 2 for Group 1A no relapse occurred while maintaining the higher dose) or failure (defined as relapse within 2 weeks of the start of Segment 2 or if at repeat cycles of Segment 1 for Group 1A, the pseudomembranes did not regress after Segment 1). Ninety-five percent confidence intervals for the relapse rate (complete success, and complete plus partial success) were calculated on the assumption of a binomial distribution. The responses were tabulated for the mITT and Per Protocol populations.
次要结局
- Percentage of Eyes With Regression in Surface Area of Existing Ligneous Pseudomembranes(Regression of pseudomembranes surface area (PSA) was assessed from baseline to the end of Segment 1, up to 5 weeks (one subject was assessed after 9 weeks due to the occurrence of a not related SAE - Varicella - between Visit 0 and Visit 1))