Back to resultsEfficacy/Safety of Human Plasminogen Eye Drop in Ligneous Conjunctivitis Patients
Primary Purpose
Ligneous Conjunctivitis
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Human Plasminogen
Sponsored by
About this trial
This is an interventional treatment trial for Ligneous Conjunctivitis focused on measuring Plasminogen Deficiency, Ligneous Conjunctivitis, Plasminogen, Ligneous Conjunctivitis in Plasminogen Deficient Patients
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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
Sites / Locations
- Indiana Hemophilia & Thrombosis Center
- Meyer Children's Hospital
- AOU Padova
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Human Plasminogen
Arm Description
Human Plasminogen Eye Drop treatment
Outcomes
Primary Outcome Measures
Percentage of Success to Prevent Pseudomembranes Relapse
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.
Secondary Outcome Measures
Percentage of Eyes With Regression in Surface Area of Existing Ligneous Pseudomembranes
The secondary endpoint was presented descriptively based on the predefined success levels: complete success (defined as regression of PSAs >90%), partial success (defined as regression of PSAs between 20% and 90%) or failure (defined as regression of PSAs <20%). The responses were tabulated for the mITT and the Per Protocol populations.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01554956
Brief Title
Efficacy/Safety of Human Plasminogen Eye Drop in Ligneous Conjunctivitis Patients
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
May 22, 2013 (Actual)
Primary Completion Date
April 25, 2014 (Actual)
Study Completion Date
December 4, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kedrion S.p.A.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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)
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ligneous Conjunctivitis
Keywords
Plasminogen Deficiency, Ligneous Conjunctivitis, Plasminogen, Ligneous Conjunctivitis in Plasminogen Deficient Patients
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Human Plasminogen
Arm Type
Experimental
Arm Description
Human Plasminogen Eye Drop treatment
Intervention Type
Biological
Intervention Name(s)
Human Plasminogen
Intervention Description
Eye Drops
Primary Outcome Measure Information:
Title
Percentage of Success to Prevent Pseudomembranes Relapse
Description
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.
Time Frame
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.
Secondary Outcome Measure Information:
Title
Percentage of Eyes With Regression in Surface Area of Existing Ligneous Pseudomembranes
Description
The secondary endpoint was presented descriptively based on the predefined success levels: complete success (defined as regression of PSAs >90%), partial success (defined as regression of PSAs between 20% and 90%) or failure (defined as regression of PSAs <20%). The responses were tabulated for the mITT and the Per Protocol populations.
Time Frame
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)
Other Pre-specified Outcome Measures:
Title
Number of Subjects Who Experience Signs and Symptoms of Sensitization.
Description
The safety parameters were presented descriptively and tabulated for the Group 1A, Group 1B and Continuation Segment safety population.
Time Frame
Signs and symptoms of sensitization were evaluated during the Part 1 and Part 2 of the study up to 7 years
Title
Number of Subjects Who Experience Adverse Events.
Description
The safety parameters were presented descriptively and tabulated for the Group 1A, Group 1B and Continuation Segment safety population.
Time Frame
AEs were collected from the screening visit and throughout the study up to 7 years
Title
Number of Subjects Who Develop Antibodies Against Bovine Aprotinin.
Description
The safety parameters were presented descriptively and tabulated for the Group 1A, Group 1B and Continuation Segment safety population.
Time Frame
The antibody development was detected during Part 1 and Part 2 of the study up to 7 years
Title
Number of Subjects Who Develop Antibodies Against Human Plasminogen.
Description
The safety parameters were presented descriptively and tabulated for the Group 1A, Group 1B and Continuation Segment safety population.
Time Frame
The antibody development was detected during the Part 1 and Part 2 of the study, up to 7 years
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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
Facility Information:
Facility Name
Indiana Hemophilia & Thrombosis Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46260
Country
United States
Facility Name
Meyer Children's Hospital
City
Florence
Country
Italy
Facility Name
AOU Padova
City
Padova
Country
Italy
12. IPD Sharing Statement
Citations:
PubMed Identifier
35346720
Citation
Caputo R, Shapiro AD, Sartori MT, Leonardi A, Jeng BH, Nakar C, Di Pasquale I, Price FW Jr, Thukral N, Suffredini AL, Pino L, Crea R, Mathew P, Calcinai M. Treatment of Ligneous Conjunctivitis with Plasminogen Eyedrops. Ophthalmology. 2022 Aug;129(8):955-957. doi: 10.1016/j.ophtha.2022.03.019. Epub 2022 Mar 26. No abstract available.
Results Reference
derived
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Efficacy/Safety of Human Plasminogen Eye Drop in Ligneous Conjunctivitis Patients
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