Treatment of Ligneous Conjunctivitis in Children With Plasminogen Deficiency

NCT05404932 | Unknown

• 1 other identifier: USASK0511ST
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

Congenital plasminogen deficiency causes impaired wound healing and growth of pseudomembranous lesions over multiple parts of the body. The most common lesions involve eyes and are known as Ligneous conjunctivitis. These can cause scarring of the sclera, vision loss and even blindness. These pseudomembranous lesions are recur after surgical excisions, administration of intra-ocular cyclosporine, autologous serum drops or corticosteroids. Clinical data shows that these growths do not worsen and do not recur after administration of plasminogen (either as concentrate or as plasma) in the eyes, locally or intravenously. As plasminogen is not available as concentrate, we are using aliquoted allogenic plasma provided by Canadian Blood Services for intra-ocular application. These will be applied to eyes multiple times a day for a period of 2 to 6 months depending on disease severity and patient response. These may be used again if ligneous conjunctivitis recurs. The patient will be followed for a period of 2 years at least. All serious adverse events will be reported to Canadian Blood Services and Health Canada as appropriate.

Conditions

Plasminogen Deficiency

Outcome Measures

Primary Outcomes (4)

• Mean difference in the size of pseudomembranous conjunctival lesion after 2 months of local administration of aliquoted plasma (reported as mean difference and percent difference from pre-administration size of pseudomembranous lesions )

  The size of pseudomembranous lesions will be measured before intervention and after 4 weeks of topical administration of aliquoted plasma in patient's conjunctiva (with/without surgical excision) 8 weeks of topical administration of plasma (with/without surgical excision). This size will be compared to the size of pseudomembranes prior to intervention. The results will be reported as mean difference and percent.

  24 months

• Time to change in the size of pseudomembranous lesions by 50% or greater with topical administration of aliquoted allogenic plasma in the affected conjunctiva.

  The presence and size of pseudomembranous lesions on the patient's conjunctiva will be assessed via ophthalmologic examination every 2-7 days for first 2 months of topical application of aliquoted plasma in affected conjunctiva. The ophthalmologic assessment will then occur at increasing intervals based on the response of patient's ligneous conjunctivitis (pseudomembranous lesions) to this therapy. Time interval to the outcome measure (change in size of pseudomembranes) will be reported as number of days from the start of administration of aliquoted plasma.

  24 months. This knowledge will be aggregated in the patient data collection form

• Difference in the visual acuity of affected eye after topical administration of aliquoted allogenic plasma into affected conjunctiva.

  The visual acuity in the affected eye will be assessed via ophthalmologic assessment using age-appropriate measures before intervention and on a periodic basis after the start of intervention. The difference in visual acuity before and after intervention will be reported as percent difference

  24 months. This information will be aggregated in data collection form

• Number of participants with development of strabismus or other visual defects in affected eye

  Assessed via clinical ophthalmologic assessment on a periodic basis after start of administration of aliquoted plasma in patient's conjunctiva

  24 months. Information will be aggregated in data collection form

Secondary Outcomes (2)

• Number of participants with recurrence of pseudomembranous lesions

  24 months

• Time to development of recurrence of pseudomembranous lesions in the eye undergoing intervention.

  24 months

Study Arms (1)

Intervention arm (aliquoted plasma application into the conjunctiva)

EXPERIMENTAL

This is the only arm of the study. The intervention is administration of aliquoted plasma provided by Canadian Blood Services in eye droppers (3 ml aliquots in 7 ml vials) in the patient's conjunctiva. The duration of therapy can be 2 to 6 months depending on response The intra-ocular drops will be administered every 1-5 hours daily in the affected eye based on disease severity and may be repeated

Drug: Aliquoted allogeneic donor plasma in patient's conjunctiva

Interventions

Aliquoted allogeneic donor plasma in patient's conjunctiva DRUG

1-2 drops of allogenic aliquoted plasma to affected eye every 1-5 hours per day based on disease severity to be weaned down based on clinical response Administration period: Two to Six months. This may be repeated based on recurrence/worsening of conjunctivitis

Intervention arm (aliquoted plasma application into the conjunctiva)

Eligibility Criteria

• Age: 1 Month - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients under the age of 18 years
• Diagnosis of plasminogen deficiency (Definition: clinical presence of pseudomembranous lesions and serum plasminogen level \< 50%)
• Ocular involvement (Ligneous Conjunctivitis) due to plasminogen deficiency

You may not qualify if:

• Patient is 18 years or older
• Patients with no plasminogen deficiency
• Patients with no ocular manifestations of plasminogen deficiency

Sponsors & Collaborators

• University of Saskatchewan: lead
• Canadian Blood Services: collaborator

Study Sites (1)

University of Saskatchewan

Saskatoon, Saskatchewan, S7N0W8, Canada

RECRUITING

Related Publications (20)

• Mehta R, Shapiro AD. Plasminogen deficiency. Haemophilia. 2008 Nov;14(6):1261-8. doi: 10.1111/j.1365-2516.2008.01825.x.

  PMID: 19141167 BACKGROUND

• Schuster V, Hugle B, Tefs K. Plasminogen deficiency. J Thromb Haemost. 2007 Dec;5(12):2315-22. doi: 10.1111/j.1538-7836.2007.02776.x. Epub 2007 Sep 26.

  PMID: 17900274 BACKGROUND

• Babcock MF, Bedford RF, Berry FA. Ligneous tracheobronchitis: an unusual cause of airway obstruction. Anesthesiology. 1987 Nov;67(5):819-21. No abstract available.

  PMID: 3674489 BACKGROUND

• Tefs K, Gueorguieva M, Klammt J, Allen CM, Aktas D, Anlar FY, Aydogdu SD, Brown D, Ciftci E, Contarini P, Dempfle CE, Dostalek M, Eisert S, Gokbuget A, Gunhan O, Hidayat AA, Hugle B, Isikoglu M, Irkec M, Joss SK, Klebe S, Kneppo C, Kurtulus I, Mehta RP, Ornek K, Schneppenheim R, Seregard S, Sweeney E, Turtschi S, Veres G, Zeitler P, Ziegler M, Schuster V. Molecular and clinical spectrum of type I plasminogen deficiency: A series of 50 patients. Blood. 2006 Nov 1;108(9):3021-6. doi: 10.1182/blood-2006-04-017350. Epub 2006 Jul 18.

  PMID: 16849641 BACKGROUND

• Bateman JB, Pettit TH, Isenberg SJ, Simons KB. Ligneous conjunctivitis: an autosomal recessive disorder. J Pediatr Ophthalmol Strabismus. 1986 May-Jun;23(3):137-40. doi: 10.3928/0191-3913-19860501-09.

  PMID: 3723296 BACKGROUND

• Schuster V, Seregard S. Ligneous conjunctivitis. Surv Ophthalmol. 2003 Jul-Aug;48(4):369-88. doi: 10.1016/s0039-6257(03)00056-0.

  PMID: 12850227 BACKGROUND

• Watts P, Agha SH, Mameesh M, Conor P, Ganesh A, Al-Mujaini A, Jewsbury H, Pathare A, Al-Rawas A. Fresh frozen plasma (Octaplas) and topical heparin in the management of ligneous conjunctivitis. J AAPOS. 2019 Feb;23(1):42-45.e1. doi: 10.1016/j.jaapos.2018.05.011. Epub 2018 Aug 27.

  PMID: 30165199 BACKGROUND

• Ku JY, Lichtinger A, Yeung SN, Kim P, Cserti-Gazdewich C, Slomovic AR. Topical fresh frozen plasma and heparin treatment of ligneous conjunctivitis in a Canadian hospital setting. Can J Ophthalmol. 2012 Oct;47(5):e27-8. doi: 10.1016/j.jcjo.2012.03.025. Epub 2012 Jul 13. No abstract available.

  PMID: 23036559 BACKGROUND

• Pergantou H, Likaki D, Fotopoulou M, Katsarou O, Xafaki P, Platokouki H. Management of ligneous conjunctivitis in a child with plasminogen deficiency. Eur J Pediatr. 2011 Oct;170(10):1333-6. doi: 10.1007/s00431-011-1483-9. Epub 2011 May 31.

  PMID: 21625933 BACKGROUND

• Suzuki T, Ikewaki J, Iwata H, Ohashi Y, Ichinose A. The first two Japanese cases of severe type I congenital plasminogen deficiency with ligneous conjunctivitis: successful treatment with direct thrombin inhibitor and fresh plasma. Am J Hematol. 2009 Jun;84(6):363-5. doi: 10.1002/ajh.21402.

  PMID: 19373890 BACKGROUND

• Shapiro AD, Menegatti M, Palla R, Boscarino M, Roberson C, Lanzi P, Bowen J, Nakar C, Janson IA, Peyvandi F. An international registry of patients with plasminogen deficiency (HISTORY). Haematologica. 2020 Mar;105(3):554-561. doi: 10.3324/haematol.2019.241158. Epub 2020 Jan 30.

  PMID: 32001536 BACKGROUND

• Khandelwal A. Allogenic plasma aliquots for use as eye drops. Information for sponsor

  BACKGROUND

• Hangul M, Tuzuner AB, Somekh I, Klein C, Patiroglu T, Unal E, Kose M. Type 1 Plasminogen Deficiency With Pulmonary Involvement: Novel Treatment and Novel Mutation. J Pediatr Hematol Oncol. 2021 May 1;43(4):e558-e560. doi: 10.1097/MPH.0000000000001951.

  PMID: 32941296 BACKGROUND

• Rouatbi A, Chebbi A, Bouguila H. Ligneous conjunctivitis due to plasminogen deficit: Diagnostic and therapeutic approach. With literature review. J Fr Ophtalmol. 2018 Dec;41(10):916-919. doi: 10.1016/j.jfo.2018.03.012. Epub 2018 Nov 12.

  PMID: 30442487 BACKGROUND

• Conforti FM, Di Felice G, Bernaschi P, Bartuli A, Bianco G, Simonetti A, Buzzonetti L, Valente P, Corsetti T. Novel plasminogen and hyaluronate sodium eye drop formulation for a patient with ligneous conjunctivitis. Am J Health Syst Pharm. 2016 Apr 15;73(8):556-61. doi: 10.2146/ajhp150395.

  PMID: 27045067 BACKGROUND

• Tu Y, Gonzalez-Gronow M, Kolomeyer AM, Cohen A, Pruzon J, Milman T, Chu DS. Adult-Onset Ligneous Conjunctivitis with Detection of a Novel Plasminogen Gene Mutation and Anti-Plasminogen IgA Antibody: A Clinicopathologic Study and Review of Literature. Semin Ophthalmol. 2016;31(6):526-31. doi: 10.3109/08820538.2015.1005319. Epub 2015 Feb 12.

  PMID: 25674820 BACKGROUND

• Ang MJ, Papageorgiou KI, Chang SH, Kohn J, Chokron Garneau H, Goldberg RA. Topical Plasminogen as Adjunctive Treatment in Recurrent Ligneous Conjunctivitis. Ophthalmic Plast Reconstr Surg. 2017 Mar/Apr;33(2):e37-e39. doi: 10.1097/IOP.0000000000000694.

  PMID: 27065432 BACKGROUND

• Heidemann DG, Williams GA, Hartzer M, Ohanian A, Citron ME. Treatment of ligneous conjunctivitis with topical plasmin and topical plasminogen. Cornea. 2003 Nov;22(8):760-2. doi: 10.1097/00003226-200311000-00009.

  PMID: 14576528 BACKGROUND

• Kizilocak H, Ozdemir N, Dikme G, Koc B, Atabek AA, Cokugras H, Iskeleli G, Donmez-Demir B, Christiansen NM, Ziegler M, Ozdag H, Schuster V, Celkan T. Treatment of plasminogen deficiency patients with fresh frozen plasma. Pediatr Blood Cancer. 2018 Feb;65(2). doi: 10.1002/pbc.26779. Epub 2017 Sep 6.

  PMID: 28876531 BACKGROUND

• Park, Benjamin J., et al.

  BACKGROUND

MeSH Terms

Conditions

Congenital Plasminogen Deficiency

Central Study Contacts

Sarah Tehseen, MBBS MSc.

CONTACT

639-998-3972; sarah.tehseen@saskhealthauthority.ca

Simona Meier, BSc, ACRP-CP.

CONTACT

306-978-8302; simona.meier@usask.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator, Assistant Professor of Pediatric Hematology and transfusion medicine

Model Details: Only one patient (and their family) with laboratory diagnosis of plasminogen deficiency and ligneous conjunctivitis will be enrolled in this study.

Study Record Dates

• First Submitted: May 12, 2022
• First Posted: June 3, 2022
• Study Start: December 15, 2022
• Primary Completion: September 30, 2024
• Study Completion: December 31, 2024
• Last Updated: December 15, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: After 12 months for 5 years
• Access Criteria: Individual physicians and research groups interested in plasminogen deficiency

Locations

CA (1)