Efficacy/Safety of Human Plasminogen Eye Drop in Ligneous Conjunctivitis Patients

NCT01554956 | Completed Phase 2 Results

• 1 other identifier: KB046
• Study Type: interventional
• Target: 12
• Locations: 2 countries
• Sites: 3

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)

Conditions

Ligneous Conjunctivitis

Keywords

Plasminogen Deficiency; Ligneous Conjunctivitis; Plasminogen; Ligneous Conjunctivitis in Plasminogen Deficient Patients

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  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 Outcomes (4)

• Number of Subjects Who Experience Signs and Symptoms of Sensitization.

  Signs and symptoms of sensitization were evaluated during the Part 1 and Part 2 of the study up to 7 years

• Number of Subjects Who Experience Adverse Events.

  AEs were collected from the screening visit and throughout the study up to 7 years

• Number of Subjects Who Develop Antibodies Against Bovine Aprotinin.

  The antibody development was detected during Part 1 and Part 2 of the study up to 7 years

Study Arms (1)

Human Plasminogen

EXPERIMENTAL

Human Plasminogen Eye Drop treatment

Biological: Human Plasminogen

Interventions

Human Plasminogen BIOLOGICAL

Eye Drops

Human Plasminogen

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Kedrion S.p.A.: lead

Study Sites (3)

Indiana Hemophilia & Thrombosis Center

Indianapolis, Indiana, 46260, United States

Location

Meyer Children's Hospital

Florence, Italy

Location

AOU Padova

Padua, Italy

Location

Related Publications (1)

• 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.

  PMID: 35346720 DERIVED

MeSH Terms

Conditions

Plasminogen Deficiency, Type I; Congenital Plasminogen Deficiency

Interventions

Plasminogen

Intervention Hierarchy (Ancestors)

Enzyme Precursors; Enzymes and Coenzymes; Beta-Globulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins; Protein Precursors

Results Point of Contact

• Title: Clinical Trial Manager
• Organization: Kedrion SpA

a.lotti@kedrion.com

+39 05831969231

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2011
• First Posted: March 15, 2012
• Study Start: May 22, 2013
• Primary Completion: April 25, 2014
• Study Completion: December 4, 2020
• Last Updated: January 25, 2023
• Results First Posted: January 25, 2023

Record last verified: 2022-06

Locations

IT (2); US (1)