Trial Outcomes & Findings for Efficacy/Safety of Human Plasminogen Eye Drop in Ligneous Conjunctivitis Patients (NCT NCT01554956)

Last Updated: 2023-01-25

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

12 participants

Primary outcome timeframe

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.

Results posted on

2023-01-25

Participant Flow

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.

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.

Unit of analysis: eyes

Participant milestones

Participant milestones
Measure	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).	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.	Continuation Segment One additional patient, who entered directly in the Part 2, without previously completing the first part of the study and 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.
Part 1 (Segment 1 and Segment 2) STARTED	4 8	7 14	0 0
Part 1 (Segment 1 and Segment 2) COMPLETED	4 8	6 12	0 0
Part 1 (Segment 1 and Segment 2) NOT COMPLETED	0 0	1 2	0 0
Part 2 (Continuation Segment) STARTED	4 8	6 12	1 2
Part 2 (Continuation Segment) COMPLETED	2 4	1 2	0 0
Part 2 (Continuation Segment) NOT COMPLETED	2 4	5 10	1 2

Reasons for withdrawal

Reasons for withdrawal
Measure	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).	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.	Continuation Segment One additional patient, who entered directly in the Part 2, without previously completing the first part of the study and 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.
Part 1 (Segment 1 and Segment 2) Withdrawal by Subject	0	1	0
Part 2 (Continuation Segment) Withdrawal by Subject	0	1	1
Part 2 (Continuation Segment) SUBJECT WAS WITHDRAWN BY THE INVESTIGATOR AT THE SITE FOR NON-IMP RELATED REASON	2	4	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group 1A n=4 Participants 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).	Group 1B n=7 Participants 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.	Continuation Segment n=1 Participants 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.	Total n=12 Participants Total of all reporting groups
Age, Categorical <=18 years	3 Participants n=5 Participants	6 Participants n=7 Participants	1 Participants n=5 Participants	10 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	4 Participants n=7 Participants	0 Participants n=5 Participants	7 Participants n=4 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	7 Participants n=7 Participants	1 Participants n=5 Participants	12 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Group 1A_mITT n=4 number of eyes Modified ITT (mITT) population consists of all eyes of subjects assigned to Groups 1A at the start of Study Segment 2, who received at least one dose of the study treatment, and underwent at least one efficacy assessment in Segment 2	Group 1B_mITT n=11 number of eyes Modified ITT (mITT) population consists of all eyes of subjects assigned to Group 1B at the start of Study Segment 2, who received at least one dose of the study treatment, and underwent at least one efficacy assessment in Segment 2	Group 1A_PP n=3 number of eyes Per Protocol population consists of all eyes of Group 1A subjects included in the mITT population, who have completed both Segment 1 and Segment 2 of the study and received at least 80% of the protocol required doses of the study treatment without any major protocol violations or exceptions that could impact the integrity of study data.	Group 1B_PP n=9 number of eyes Per Protocol population consists all eyes of Group 1B subjects included in the mITT population, who have completed both Segment 1 and Segment 2 of the study and received at least 80% of the protocol required doses of the study treatment without any major protocol violations or exceptions that could impact the integrity of study data.
Percentage of Success to Prevent Pseudomembranes Relapse success	75 percentage of eyes Interval 19.4 to 99.4	81.8 percentage of eyes Interval 48.2 to 97.7	100 percentage of eyes Interval 29.2 to 100.0	100 percentage of eyes Interval 66.4 to 100.0
Percentage of Success to Prevent Pseudomembranes Relapse partial success	0 percentage of eyes Interval 0.0 to 60.2	18.2 percentage of eyes Interval 2.3 to 51.8	0 percentage of eyes Interval 0.0 to 70.8	0 percentage of eyes Interval 0.0 to 33.6
Percentage of Success to Prevent Pseudomembranes Relapse failure	25 percentage of eyes Interval 0.6 to 80.6	0 percentage of eyes Interval 0.0 to 28.5	0 percentage of eyes Interval 0.0 to 70.8	0 percentage of eyes Interval 0.0 to 33.6

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Group 1A_mITT n=15 number of eyes Modified ITT (mITT) population consists of all eyes of subjects assigned to Groups 1A at the start of Study Segment 2, who received at least one dose of the study treatment, and underwent at least one efficacy assessment in Segment 2	Group 1B_mITT n=12 number of eyes Modified ITT (mITT) population consists of all eyes of subjects assigned to Group 1B at the start of Study Segment 2, who received at least one dose of the study treatment, and underwent at least one efficacy assessment in Segment 2	Group 1A_PP Per Protocol population consists of all eyes of Group 1A subjects included in the mITT population, who have completed both Segment 1 and Segment 2 of the study and received at least 80% of the protocol required doses of the study treatment without any major protocol violations or exceptions that could impact the integrity of study data.	Group 1B_PP Per Protocol population consists all eyes of Group 1B subjects included in the mITT population, who have completed both Segment 1 and Segment 2 of the study and received at least 80% of the protocol required doses of the study treatment without any major protocol violations or exceptions that could impact the integrity of study data.
Percentage of Eyes With Regression in Surface Area of Existing Ligneous Pseudomembranes failure	33.3 percentage of eyes Interval 11.8 to 61.6	16.7 percentage of eyes Interval 2.1 to 48.4	—	—
Percentage of Eyes With Regression in Surface Area of Existing Ligneous Pseudomembranes complete success	20 percentage of eyes Interval 4.3 to 48.1	25 percentage of eyes Interval 5.5 to 57.2	—	—
Percentage of Eyes With Regression in Surface Area of Existing Ligneous Pseudomembranes partial success	46.7 percentage of eyes Interval 21.3 to 73.4	58.3 percentage of eyes Interval 27.7 to 84.8	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Group 1A_mITT n=4 Participants Modified ITT (mITT) population consists of all eyes of subjects assigned to Groups 1A at the start of Study Segment 2, who received at least one dose of the study treatment, and underwent at least one efficacy assessment in Segment 2	Group 1B_mITT n=7 Participants Modified ITT (mITT) population consists of all eyes of subjects assigned to Group 1B at the start of Study Segment 2, who received at least one dose of the study treatment, and underwent at least one efficacy assessment in Segment 2	Group 1A_PP n=11 Participants Per Protocol population consists of all eyes of Group 1A subjects included in the mITT population, who have completed both Segment 1 and Segment 2 of the study and received at least 80% of the protocol required doses of the study treatment without any major protocol violations or exceptions that could impact the integrity of study data.	Group 1B_PP Per Protocol population consists all eyes of Group 1B subjects included in the mITT population, who have completed both Segment 1 and Segment 2 of the study and received at least 80% of the protocol required doses of the study treatment without any major protocol violations or exceptions that could impact the integrity of study data.
Number of Subjects Who Experience Signs and Symptoms of Sensitization. Cataract	0 number of subjects	0 number of subjects	1 number of subjects	—
Number of Subjects Who Experience Signs and Symptoms of Sensitization. Conjunctival oedema	0 number of subjects	0 number of subjects	2 number of subjects	—
Number of Subjects Who Experience Signs and Symptoms of Sensitization. Conjunctivitis	0 number of subjects	0 number of subjects	4 number of subjects	—
Number of Subjects Who Experience Signs and Symptoms of Sensitization. Eye swelling	0 number of subjects	0 number of subjects	2 number of subjects	—
Number of Subjects Who Experience Signs and Symptoms of Sensitization. Pinguecula	0 number of subjects	0 number of subjects	1 number of subjects	—
Number of Subjects Who Experience Signs and Symptoms of Sensitization. Number of Subjects with Ocular Adverse Events	1 number of subjects	4 number of subjects	8 number of subjects	—
Number of Subjects Who Experience Signs and Symptoms of Sensitization. Conjunctivitis bacterial	1 number of subjects	0 number of subjects	2 number of subjects	—
Number of Subjects Who Experience Signs and Symptoms of Sensitization. Ectropion	0 number of subjects	1 number of subjects	0 number of subjects	—
Number of Subjects Who Experience Signs and Symptoms of Sensitization. Eye haemorrhage	0 number of subjects	1 number of subjects	0 number of subjects	—
Number of Subjects Who Experience Signs and Symptoms of Sensitization. Eye pain	0 number of subjects	1 number of subjects	1 number of subjects	—
Number of Subjects Who Experience Signs and Symptoms of Sensitization. Eyelid margin crusting	0 number of subjects	1 number of subjects	0 number of subjects	—
Number of Subjects Who Experience Signs and Symptoms of Sensitization. Lacrimation increased	0 number of subjects	1 number of subjects	0 number of subjects	—
Number of Subjects Who Experience Signs and Symptoms of Sensitization. Ocular hyperaemia	0 number of subjects	1 number of subjects	3 number of subjects	—
Number of Subjects Who Experience Signs and Symptoms of Sensitization. Ocular hypertension	0 number of subjects	1 number of subjects	2 number of subjects	—
Number of Subjects Who Experience Signs and Symptoms of Sensitization. Blepharitis	0 number of subjects	0 number of subjects	1 number of subjects	—
Number of Subjects Who Experience Signs and Symptoms of Sensitization. Chalazion	0 number of subjects	0 number of subjects	1 number of subjects	—
Number of Subjects Who Experience Signs and Symptoms of Sensitization. Conjunctival disorder	0 number of subjects	0 number of subjects	1 number of subjects	—
Number of Subjects Who Experience Signs and Symptoms of Sensitization. Eye discharge	0 number of subjects	0 number of subjects	3 number of subjects	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Group 1A_mITT n=4 Participants Modified ITT (mITT) population consists of all eyes of subjects assigned to Groups 1A at the start of Study Segment 2, who received at least one dose of the study treatment, and underwent at least one efficacy assessment in Segment 2	Group 1B_mITT n=7 Participants Modified ITT (mITT) population consists of all eyes of subjects assigned to Group 1B at the start of Study Segment 2, who received at least one dose of the study treatment, and underwent at least one efficacy assessment in Segment 2	Group 1A_PP n=11 Participants Per Protocol population consists of all eyes of Group 1A subjects included in the mITT population, who have completed both Segment 1 and Segment 2 of the study and received at least 80% of the protocol required doses of the study treatment without any major protocol violations or exceptions that could impact the integrity of study data.	Group 1B_PP Per Protocol population consists all eyes of Group 1B subjects included in the mITT population, who have completed both Segment 1 and Segment 2 of the study and received at least 80% of the protocol required doses of the study treatment without any major protocol violations or exceptions that could impact the integrity of study data.
Number of Subjects Who Experience Adverse Events. Number of Subjects with Adverse Events	4 number of subjects	7 number of subjects	10 number of subjects	—
Number of Subjects Who Experience Adverse Events. Number of Subjects with Causally-Related Adverse Events	0 number of subjects	3 number of subjects	6 number of subjects	—
Number of Subjects Who Experience Adverse Events. Number of Subjects Prematurely Withdrawn due to Adverse Events	0 number of subjects	0 number of subjects	3 number of subjects	—
Number of Subjects Who Experience Adverse Events. Number of Subjects with Serious Adverse Events	2 number of subjects	3 number of subjects	0 number of subjects	—
Number of Subjects Who Experience Adverse Events. Number of Subjects with Causally-Related Serious Adverse Events	0 number of subjects	0 number of subjects	2 number of subjects	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

The safety parameters were presented descriptively and tabulated for the Group 1A, Group 1B and Continuation Segment safety population.

Outcome measures

Outcome measures
Measure	Group 1A_mITT n=4 Participants Modified ITT (mITT) population consists of all eyes of subjects assigned to Groups 1A at the start of Study Segment 2, who received at least one dose of the study treatment, and underwent at least one efficacy assessment in Segment 2	Group 1B_mITT n=7 Participants Modified ITT (mITT) population consists of all eyes of subjects assigned to Group 1B at the start of Study Segment 2, who received at least one dose of the study treatment, and underwent at least one efficacy assessment in Segment 2	Group 1A_PP n=11 Participants Per Protocol population consists of all eyes of Group 1A subjects included in the mITT population, who have completed both Segment 1 and Segment 2 of the study and received at least 80% of the protocol required doses of the study treatment without any major protocol violations or exceptions that could impact the integrity of study data.	Group 1B_PP Per Protocol population consists all eyes of Group 1B subjects included in the mITT population, who have completed both Segment 1 and Segment 2 of the study and received at least 80% of the protocol required doses of the study treatment without any major protocol violations or exceptions that could impact the integrity of study data.
Number of Subjects Who Develop Antibodies Against Bovine Aprotinin. New antibody development	0 number of subjects	3 number of subjects	3 number of subjects	—
Number of Subjects Who Develop Antibodies Against Bovine Aprotinin. Antibody Increasing	0 number of subjects	1 number of subjects	0 number of subjects	—
Number of Subjects Who Develop Antibodies Against Bovine Aprotinin. Antibody Decreasing	0 number of subjects	1 number of subjects	0 number of subjects	—
Number of Subjects Who Develop Antibodies Against Bovine Aprotinin. Antibody no changes	0 number of subjects	1 number of subjects	0 number of subjects	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Group 1A_mITT n=4 Participants Modified ITT (mITT) population consists of all eyes of subjects assigned to Groups 1A at the start of Study Segment 2, who received at least one dose of the study treatment, and underwent at least one efficacy assessment in Segment 2	Group 1B_mITT n=7 Participants Modified ITT (mITT) population consists of all eyes of subjects assigned to Group 1B at the start of Study Segment 2, who received at least one dose of the study treatment, and underwent at least one efficacy assessment in Segment 2	Group 1A_PP n=11 Participants Per Protocol population consists of all eyes of Group 1A subjects included in the mITT population, who have completed both Segment 1 and Segment 2 of the study and received at least 80% of the protocol required doses of the study treatment without any major protocol violations or exceptions that could impact the integrity of study data.	Group 1B_PP Per Protocol population consists all eyes of Group 1B subjects included in the mITT population, who have completed both Segment 1 and Segment 2 of the study and received at least 80% of the protocol required doses of the study treatment without any major protocol violations or exceptions that could impact the integrity of study data.
Number of Subjects Who Develop Antibodies Against Human Plasminogen.	0 number of subjects	1 number of subjects	1 number of subjects	—

Adverse Events

Group 1A

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

Group 1B

Serious events: 3 serious events

Other events: 7 other events

Deaths: 0 deaths

Continuation Segment

Serious events: 3 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Group 1A n=4 participants at risk Patients with eyes showing complete pseudomembranes regression (defined as \>90%) who have received IMP at a dose of 2 drops/eye 6 times/day for 8 weeks.	Group 1B n=7 participants at risk Patients with eyes showing partial (defined as between 20% and 90%) or no pseudomembranes regression (defined as \<20%) were to undergo surgery, within 2 weeks from the end of Segment 1, to remove the pseudomembranes. After surgery, patients were to continue receiving IMP (2 drops/eye) for an additional 8 weeks, at the decreasing frequency.	Continuation Segment n=11 participants at risk 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 part 1 and one additional patient, who entered directly, without previously completing the first part of the study were to receive IMP at a dosage regimen of 2 drops/eye 4 to 6 times/day at Investigator's discretion.
Investigations Blood alkaline phosphatase increased	25.0% 1/4 • AEs were collected from the screening visit and throughout the study up to 7 years AEs were collected by spontaneous reporting by the patient, by review of the Subject Diaries, and, during the visits at site, by asking the patient non-leading questions about how they felt since their last study visit	14.3% 1/7 • AEs were collected from the screening visit and throughout the study up to 7 years AEs were collected by spontaneous reporting by the patient, by review of the Subject Diaries, and, during the visits at site, by asking the patient non-leading questions about how they felt since their last study visit	0.00% 0/11 • AEs were collected from the screening visit and throughout the study up to 7 years AEs were collected by spontaneous reporting by the patient, by review of the Subject Diaries, and, during the visits at site, by asking the patient non-leading questions about how they felt since their last study visit
Investigations Drug specific antibody present	0.00% 0/4 • AEs were collected from the screening visit and throughout the study up to 7 years AEs were collected by spontaneous reporting by the patient, by review of the Subject Diaries, and, during the visits at site, by asking the patient non-leading questions about how they felt since their last study visit	14.3% 1/7 • AEs were collected from the screening visit and throughout the study up to 7 years AEs were collected by spontaneous reporting by the patient, by review of the Subject Diaries, and, during the visits at site, by asking the patient non-leading questions about how they felt since their last study visit	9.1% 1/11 • AEs were collected from the screening visit and throughout the study up to 7 years AEs were collected by spontaneous reporting by the patient, by review of the Subject Diaries, and, during the visits at site, by asking the patient non-leading questions about how they felt since their last study visit
Eye disorders Conjunctivitis	0.00% 0/4 • AEs were collected from the screening visit and throughout the study up to 7 years AEs were collected by spontaneous reporting by the patient, by review of the Subject Diaries, and, during the visits at site, by asking the patient non-leading questions about how they felt since their last study visit	0.00% 0/7 • AEs were collected from the screening visit and throughout the study up to 7 years AEs were collected by spontaneous reporting by the patient, by review of the Subject Diaries, and, during the visits at site, by asking the patient non-leading questions about how they felt since their last study visit	9.1% 1/11 • AEs were collected from the screening visit and throughout the study up to 7 years AEs were collected by spontaneous reporting by the patient, by review of the Subject Diaries, and, during the visits at site, by asking the patient non-leading questions about how they felt since their last study visit
Hepatobiliary disorders Autoimmune hepatitis	25.0% 1/4 • AEs were collected from the screening visit and throughout the study up to 7 years AEs were collected by spontaneous reporting by the patient, by review of the Subject Diaries, and, during the visits at site, by asking the patient non-leading questions about how they felt since their last study visit	0.00% 0/7 • AEs were collected from the screening visit and throughout the study up to 7 years AEs were collected by spontaneous reporting by the patient, by review of the Subject Diaries, and, during the visits at site, by asking the patient non-leading questions about how they felt since their last study visit	0.00% 0/11 • AEs were collected from the screening visit and throughout the study up to 7 years AEs were collected by spontaneous reporting by the patient, by review of the Subject Diaries, and, during the visits at site, by asking the patient non-leading questions about how they felt since their last study visit
Metabolism and nutrition disorders Diabetic ketoacidosis	0.00% 0/4 • AEs were collected from the screening visit and throughout the study up to 7 years AEs were collected by spontaneous reporting by the patient, by review of the Subject Diaries, and, during the visits at site, by asking the patient non-leading questions about how they felt since their last study visit	0.00% 0/7 • AEs were collected from the screening visit and throughout the study up to 7 years AEs were collected by spontaneous reporting by the patient, by review of the Subject Diaries, and, during the visits at site, by asking the patient non-leading questions about how they felt since their last study visit	9.1% 1/11 • AEs were collected from the screening visit and throughout the study up to 7 years AEs were collected by spontaneous reporting by the patient, by review of the Subject Diaries, and, during the visits at site, by asking the patient non-leading questions about how they felt since their last study visit
Infections and infestations Varicella	0.00% 0/4 • AEs were collected from the screening visit and throughout the study up to 7 years AEs were collected by spontaneous reporting by the patient, by review of the Subject Diaries, and, during the visits at site, by asking the patient non-leading questions about how they felt since their last study visit	14.3% 1/7 • AEs were collected from the screening visit and throughout the study up to 7 years AEs were collected by spontaneous reporting by the patient, by review of the Subject Diaries, and, during the visits at site, by asking the patient non-leading questions about how they felt since their last study visit	0.00% 0/11 • AEs were collected from the screening visit and throughout the study up to 7 years AEs were collected by spontaneous reporting by the patient, by review of the Subject Diaries, and, during the visits at site, by asking the patient non-leading questions about how they felt since their last study visit

Other adverse events

Additional Information

Clinical Trial Manager

Kedrion SpA

Phone: +39 05831969231

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Any results communication will be examined by the PIs and Sponsor 60 days before the submission. Sponsor should receive one copy of each publication proposed. The comments of Sponsor should be issued not beyond 60 days. PI cannot publish data which are considered to be common to such a study without the consent of the other PIs and previous review of Sponsor. In case of disagreement between the PIs, the the senior author and the Sponsor will discuss to find a common position.
Publication restrictions are in place

Restriction type: OTHER