Ligneous Conjunctivitis
Conditions
Keywords
Plasminogen Deficiency, Ligneous Conjunctivitis, Plasminogen, Ligneous Conjunctivitis in Plasminogen Deficient Patients
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.
Interventions
BIOLOGICALHuman Plasminogen
Eye Drops
Sponsors
Kedrion S.p.A.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Success to Prevent Pseudomembranes Relapse | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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 | The safety parameters were presented descriptively and tabulated for the Group 1A, Group 1B and Continuation Segment safety population. |
| Number of Subjects Who Experience Adverse Events. | AEs were collected from the screening visit and throughout the study up to 7 years | The safety parameters were presented descriptively and tabulated for the Group 1A, Group 1B and Continuation Segment safety population. |
| 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 | The safety parameters were presented descriptively and tabulated for the Group 1A, Group 1B and Continuation Segment safety population. |
| Number of Subjects Who Develop Antibodies Against Human Plasminogen. | The antibody development was detected during the Part 1 and Part 2 of the study, up to 7 years | The safety parameters were presented descriptively and tabulated for the Group 1A, Group 1B and Continuation Segment safety population. |
Countries
Italy, United States
Participant flow
Recruitment details
A total of 13 subjects were screened (11 in Part 1 and 2 in Part 2) of which 12 subjects (24 eyes) were enrolled in the study (11 in Part 1 and 1 in Part 2) and 1 subject who failed screening in Part 2. All subjects enrolled in Part 1 of the study were symptomatic at screening, so all were included in Group 1. No subjects were included in Group 2.
Pre-assignment details
The study was divided in Part 1 (Segment 1 and Segment 2) and Part 2 (Continuation Segment). The screening procedures were performed within a 30-day window prior to receiving the first study IMP administration. A second screening for additional two subjects was performed before entering in the Part 2 of the study.
Participants by arm
| Arm | Count |
|---|---|
| Group 1A Symptomatic subjects with ocular pseudomembranes in one or both eyes at screening who received the IMP for 4 weeks (Segment 1) and with eyes showing complete pseudomembranes regression (defined as \>90%). They have continued to received IMP at a reduced dose for an additional 8 weeks (Segment 2). | 4 |
| Group 1B Symptomatic subjects with ocular pseudomembranes in one or both eyes at screening who received the IMP for 4 weeks (Segment 1) and with eyes showing partial (defined as between 20% and 90%) or no pseudomembranes regression (defined as \<20%). They were to undergo surgery, within 2 weeks from the end of Segment 1, to remove the pseudomembranes. After surgery, subjects were to continue receiving IMP for an additional 8 weeks, at the decreasing frequency. | 7 |
| Continuation Segment Subjects demonstrating complete treatment success (defined as regression of pseudomembranes in Segment 1 and no relapse of pseudomembranes through Segment 2) at the end of the Segment 2 were entered the Continuation Segment and one additional patient, who entered directly in the Part 2, without previously completing the first part of the study. | 1 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Part 1 (Segment 1 and Segment 2) | Withdrawal by Subject | 0 | 1 | 0 |
| Part 2 (Continuation Segment) | SUBJECT WAS WITHDRAWN BY THE INVESTIGATOR AT THE SITE FOR NON-IMP RELATED REASON | 2 | 4 | 0 |
| Part 2 (Continuation Segment) | Withdrawal by Subject | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Group 1A | Group 1B | Continuation Segment | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 3 Participants | 6 Participants | 1 Participants | 10 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 7 Participants | 1 Participants | 12 Participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 0 Participants | 7 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 1 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 7 | 0 / 11 |
| other Total, other adverse events | 4 / 4 | 7 / 7 | 10 / 11 |
| serious Total, serious adverse events | 2 / 4 | 3 / 7 | 3 / 11 |
Outcome results
Primary
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.
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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1A_mITT | Percentage of Success to Prevent Pseudomembranes Relapse | success | 75 percentage of eyes |
| Group 1A_mITT | Percentage of Success to Prevent Pseudomembranes Relapse | failure | 25 percentage of eyes |
| Group 1A_mITT | Percentage of Success to Prevent Pseudomembranes Relapse | partial success | 0 percentage of eyes |
| Group 1B_mITT | Percentage of Success to Prevent Pseudomembranes Relapse | success | 81.8 percentage of eyes |
| Group 1B_mITT | Percentage of Success to Prevent Pseudomembranes Relapse | failure | 0 percentage of eyes |
| Group 1B_mITT | Percentage of Success to Prevent Pseudomembranes Relapse | partial success | 18.2 percentage of eyes |
| Group 1A_PP | Percentage of Success to Prevent Pseudomembranes Relapse | partial success | 0 percentage of eyes |
| Group 1A_PP | Percentage of Success to Prevent Pseudomembranes Relapse | success | 100 percentage of eyes |
| Group 1A_PP | Percentage of Success to Prevent Pseudomembranes Relapse | failure | 0 percentage of eyes |
| Group 1B_PP | Percentage of Success to Prevent Pseudomembranes Relapse | success | 100 percentage of eyes |
| Group 1B_PP | Percentage of Success to Prevent Pseudomembranes Relapse | failure | 0 percentage of eyes |
| Group 1B_PP | Percentage of Success to Prevent Pseudomembranes Relapse | partial success | 0 percentage of eyes |
Secondary
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.
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)
Population: The first Part of the Study was divided in two segments: Segment 1, where all patients received the same intervention and Segment 2 where, depending on the outcome of Segment 1, patients were assigned to Group 1A (in case of complete pseudomembranes regression) or Group 1B (in case of no or partial pseudomembranes regression), receiving different intervention.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1A_mITT | Percentage of Eyes With Regression in Surface Area of Existing Ligneous Pseudomembranes | complete success | 20 percentage of eyes |
| Group 1A_mITT | Percentage of Eyes With Regression in Surface Area of Existing Ligneous Pseudomembranes | partial success | 46.7 percentage of eyes |
| Group 1A_mITT | Percentage of Eyes With Regression in Surface Area of Existing Ligneous Pseudomembranes | failure | 33.3 percentage of eyes |
| Group 1B_mITT | Percentage of Eyes With Regression in Surface Area of Existing Ligneous Pseudomembranes | complete success | 25 percentage of eyes |
| Group 1B_mITT | Percentage of Eyes With Regression in Surface Area of Existing Ligneous Pseudomembranes | partial success | 58.3 percentage of eyes |
| Group 1B_mITT | Percentage of Eyes With Regression in Surface Area of Existing Ligneous Pseudomembranes | failure | 16.7 percentage of eyes |
Other Pre-specified
Number of Subjects Who Develop Antibodies Against Bovine Aprotinin.
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
Population: All participants enrolled in the study underwent to immunogenicity assessment. Participans in Part 1 was 11: 4 from Group 1A and 7 from Group 1B. Participants analysed in Part 2 was 11: 4 from Part 1-Group 1A, 6 from Part 1-Group 1B and 1 new patient enrolled directly in Part 2.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1A_mITT | Number of Subjects Who Develop Antibodies Against Bovine Aprotinin. | Antibody Decreasing | 0 number of subjects |
| Group 1A_mITT | Number of Subjects Who Develop Antibodies Against Bovine Aprotinin. | Antibody no changes | 0 number of subjects |
| Group 1A_mITT | Number of Subjects Who Develop Antibodies Against Bovine Aprotinin. | Antibody Increasing | 0 number of subjects |
| Group 1A_mITT | Number of Subjects Who Develop Antibodies Against Bovine Aprotinin. | New antibody development | 0 number of subjects |
| Group 1B_mITT | Number of Subjects Who Develop Antibodies Against Bovine Aprotinin. | New antibody development | 3 number of subjects |
| Group 1B_mITT | Number of Subjects Who Develop Antibodies Against Bovine Aprotinin. | Antibody Increasing | 1 number of subjects |
| Group 1B_mITT | Number of Subjects Who Develop Antibodies Against Bovine Aprotinin. | Antibody no changes | 1 number of subjects |
| Group 1B_mITT | Number of Subjects Who Develop Antibodies Against Bovine Aprotinin. | Antibody Decreasing | 1 number of subjects |
| Group 1A_PP | Number of Subjects Who Develop Antibodies Against Bovine Aprotinin. | Antibody no changes | 0 number of subjects |
| Group 1A_PP | Number of Subjects Who Develop Antibodies Against Bovine Aprotinin. | New antibody development | 3 number of subjects |
| Group 1A_PP | Number of Subjects Who Develop Antibodies Against Bovine Aprotinin. | Antibody Increasing | 0 number of subjects |
| Group 1A_PP | Number of Subjects Who Develop Antibodies Against Bovine Aprotinin. | Antibody Decreasing | 0 number of subjects |
Other Pre-specified
Number of Subjects Who Develop Antibodies Against Human Plasminogen.
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1A_mITT | Number of Subjects Who Develop Antibodies Against Human Plasminogen. | 0 number of subjects |
| Group 1B_mITT | Number of Subjects Who Develop Antibodies Against Human Plasminogen. | 1 number of subjects |
| Group 1A_PP | Number of Subjects Who Develop Antibodies Against Human Plasminogen. | 1 number of subjects |
Other Pre-specified
Number of Subjects Who Experience Adverse Events.
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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1A_mITT | Number of Subjects Who Experience Adverse Events. | Number of Subjects with Serious Adverse Events | 2 number of subjects |
| Group 1A_mITT | Number of Subjects Who Experience Adverse Events. | Number of Subjects Prematurely Withdrawn due to Adverse Events | 0 number of subjects |
| Group 1A_mITT | Number of Subjects Who Experience Adverse Events. | Number of Subjects with Adverse Events | 4 number of subjects |
| Group 1A_mITT | Number of Subjects Who Experience Adverse Events. | Number of Subjects with Causally-Related Adverse Events | 0 number of subjects |
| Group 1A_mITT | Number of Subjects Who Experience Adverse Events. | Number of Subjects with Causally-Related Serious Adverse Events | 0 number of subjects |
| Group 1B_mITT | Number of Subjects Who Experience Adverse Events. | Number of Subjects Prematurely Withdrawn due to Adverse Events | 0 number of subjects |
| Group 1B_mITT | Number of Subjects Who Experience Adverse Events. | Number of Subjects with Adverse Events | 7 number of subjects |
| Group 1B_mITT | Number of Subjects Who Experience Adverse Events. | Number of Subjects with Causally-Related Adverse Events | 3 number of subjects |
| Group 1B_mITT | Number of Subjects Who Experience Adverse Events. | Number of Subjects with Serious Adverse Events | 3 number of subjects |
| Group 1B_mITT | Number of Subjects Who Experience Adverse Events. | Number of Subjects with Causally-Related Serious Adverse Events | 0 number of subjects |
| Group 1A_PP | Number of Subjects Who Experience Adverse Events. | Number of Subjects with Causally-Related Serious Adverse Events | 2 number of subjects |
| Group 1A_PP | Number of Subjects Who Experience Adverse Events. | Number of Subjects with Serious Adverse Events | 0 number of subjects |
| Group 1A_PP | Number of Subjects Who Experience Adverse Events. | Number of Subjects with Adverse Events | 10 number of subjects |
| Group 1A_PP | Number of Subjects Who Experience Adverse Events. | Number of Subjects Prematurely Withdrawn due to Adverse Events | 3 number of subjects |
| Group 1A_PP | Number of Subjects Who Experience Adverse Events. | Number of Subjects with Causally-Related Adverse Events | 6 number of subjects |
Other Pre-specified
Number of Subjects Who Experience Signs and Symptoms of Sensitization.
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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group 1A_mITT | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Conjunctival disorder | 0 number of subjects |
| Group 1A_mITT | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Eye pain | 0 number of subjects |
| Group 1A_mITT | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Conjunctival oedema | 0 number of subjects |
| Group 1A_mITT | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Conjunctivitis | 0 number of subjects |
| Group 1A_mITT | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Eye discharge | 0 number of subjects |
| Group 1A_mITT | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Eyelid margin crusting | 0 number of subjects |
| Group 1A_mITT | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Eye swelling | 0 number of subjects |
| Group 1A_mITT | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Pinguecula | 0 number of subjects |
| Group 1A_mITT | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Blepharitis | 0 number of subjects |
| Group 1A_mITT | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Lacrimation increased | 0 number of subjects |
| Group 1A_mITT | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Ectropion | 0 number of subjects |
| Group 1A_mITT | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Ocular hyperaemia | 0 number of subjects |
| Group 1A_mITT | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Ocular hypertension | 0 number of subjects |
| Group 1A_mITT | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Number of Subjects with Ocular Adverse Events | 1 number of subjects |
| Group 1A_mITT | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Eye haemorrhage | 0 number of subjects |
| Group 1A_mITT | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Cataract | 0 number of subjects |
| Group 1A_mITT | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Chalazion | 0 number of subjects |
| Group 1A_mITT | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Conjunctivitis bacterial | 1 number of subjects |
| Group 1B_mITT | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Number of Subjects with Ocular Adverse Events | 4 number of subjects |
| Group 1B_mITT | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Conjunctival disorder | 0 number of subjects |
| Group 1B_mITT | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Cataract | 0 number of subjects |
| Group 1B_mITT | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Lacrimation increased | 1 number of subjects |
| Group 1B_mITT | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Conjunctival oedema | 0 number of subjects |
| Group 1B_mITT | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Eye pain | 1 number of subjects |
| Group 1B_mITT | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Blepharitis | 0 number of subjects |
| Group 1B_mITT | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Conjunctivitis | 0 number of subjects |
| Group 1B_mITT | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Conjunctivitis bacterial | 0 number of subjects |
| Group 1B_mITT | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Eye haemorrhage | 1 number of subjects |
| Group 1B_mITT | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Eye discharge | 0 number of subjects |
| Group 1B_mITT | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Ocular hyperaemia | 1 number of subjects |
| Group 1B_mITT | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Ectropion | 1 number of subjects |
| Group 1B_mITT | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Eye swelling | 0 number of subjects |
| Group 1B_mITT | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Eyelid margin crusting | 1 number of subjects |
| Group 1B_mITT | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Chalazion | 0 number of subjects |
| Group 1B_mITT | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Pinguecula | 0 number of subjects |
| Group 1B_mITT | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Ocular hypertension | 1 number of subjects |
| Group 1A_PP | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Pinguecula | 1 number of subjects |
| Group 1A_PP | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Number of Subjects with Ocular Adverse Events | 8 number of subjects |
| Group 1A_PP | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Conjunctivitis bacterial | 2 number of subjects |
| Group 1A_PP | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Ectropion | 0 number of subjects |
| Group 1A_PP | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Eye haemorrhage | 0 number of subjects |
| Group 1A_PP | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Eye pain | 1 number of subjects |
| Group 1A_PP | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Eyelid margin crusting | 0 number of subjects |
| Group 1A_PP | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Lacrimation increased | 0 number of subjects |
| Group 1A_PP | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Ocular hyperaemia | 3 number of subjects |
| Group 1A_PP | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Ocular hypertension | 2 number of subjects |
| Group 1A_PP | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Blepharitis | 1 number of subjects |
| Group 1A_PP | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Cataract | 1 number of subjects |
| Group 1A_PP | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Chalazion | 1 number of subjects |
| Group 1A_PP | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Conjunctival disorder | 1 number of subjects |
| Group 1A_PP | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Conjunctival oedema | 2 number of subjects |
| Group 1A_PP | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Conjunctivitis | 4 number of subjects |
| Group 1A_PP | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Eye discharge | 3 number of subjects |
| Group 1A_PP | Number of Subjects Who Experience Signs and Symptoms of Sensitization. | Eye swelling | 2 number of subjects |