Ligneous ConjunctivitisPhase 2/3NCT01554956
Efficacy/Safety of Human Plasminogen Eye Drop in Ligneous Conjunctivitis Patients
A Phase 2/3 study testing Human Plasminogen in people with Ligneous Conjunctivitis, run by Kedrion S.p.A. at 3 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Ligneous Conjunctivitis
- What is being tested?
- Human Plasminogen
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 22 May 2013to 4 Dec 2020
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
United States1 site
Indiana Hemophilia & Thrombosis Center
Indianapolis, Indiana, 46260
About this study
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
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)
Read the 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.
- Conditions
- Ligneous Conjunctivitis
- Being tested
- Human Plasminogen
- Keywords
- Plasminogen Deficiency, Ligneous Conjunctivitis, Plasminogen, Ligneous Conjunctivitis in Plasminogen Deficient Patients
- Medical subject headings
- Plasminogen Deficiency, Type I, Congenital Plasminogen Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Human PlasminogenBiological
Eye Drops
| Study group | Role | What they receive |
|---|---|---|
| Human Plasminogen | Experimental | Human Plasminogen Eye Drop treatment Receives: Biological: Human Plasminogen |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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 outcomes (1)
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.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2012 (estimated)
- Study start22 May 2013
- Primary completion25 Apr 2014
- Study completion4 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ligneous ConjunctivitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kedrion S.p.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01554956
- Sponsor's protocol ID
- KB046
- Status last verified
- Jun 2022
- First submitted
- 20 Dec 2011
- Last updated
- 25 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 35346720
Study at a glance
From the registry record, last updated by the sponsor on 25 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01554956
- Acronym / sponsor ID
- KB046
- Conditions
- Ligneous Conjunctivitis
- Keywords
- Plasminogen Deficiency, Ligneous Conjunctivitis, Plasminogen, Ligneous Conjunctivitis in Plasminogen Deficient Patients
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Kedrion S.p.A.Industry (pharma, biotech, devices)
- Study start
- 22 May 2013 (actual)
- Primary completion
- 25 Apr 2014 (actual)
- Study completion
- 4 Dec 2020 (actual)
- First posted
- 15 Mar 2012 (estimated)
- Results
- Posted 25 Jan 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Human Plasminogen | Experimental | Biological: Human PlasminogenHuman Plasminogen Eye Drop treatment |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Human PlasminogenEye Drops | Biological | Human Plasminogen |
Primary outcome
Percentage of Success to Prevent Pseudomembranes Relapse
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.
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.
1 secondary outcome
Percentage of Eyes With Regression in Surface Area of Existing Ligneous Pseudomembranes
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35346720Caputo 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.
Related trials for Ligneous Conjunctivitis
Enrolling by invitationPhase 3
Allogenic Plasma Aliquots in the Treatment of Ligneous Conjunctivitis
Ligneous Conjunctivitis, Left Eye
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Human Plasminogen in people with Ligneous Conjunctivitis, run by Kedrion S.p.A. at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Italy, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Jan 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Success to Prevent Pseudomembranes Relapse (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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01554956, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jan 2023.