Trial Outcomes & Findings for REC 0/0559 Eye Drops for Treatment of Moderate and Severe Neurotrophic Keratitis in Adult Patients (NCT NCT04276558)

Last Updated: 2025-05-14

Results Overview

The primary endpoint of this study is the percentage of patients achieving complete corneal healing of PED or corneal ulcer at Week 8, defined as no corneal fluorescein staining in the area of the PED or corneal ulcer as assessed by an independent central reading centre.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

108 participants

Primary outcome timeframe

At week 8

Results posted on

2025-05-14

Participant Flow

Overall, 108 patients were randomised, and all of them received at least one dose of study drug. A total of 83 patients (76.9%) completed the 8-week treatment period and 88 patients (81.5%) completed the study regardless of the study treatment duration. The drug was instilled in 1 study eye per participant.

Unit of analysis: eye

Participant milestones

Participant milestones
Measure	Dose 1 - 0.5 µg/Day Dose of study drug per day: 0.5 µg/day Study drug concentration: 5 µg/mL MT8 given 1 drop QID Udonitrectag: Eye drop solution in single dose unit. Vehicle: Eye drop solution with no active substance in single dose unit.	Dose 2 - 2.5 µg/Day Dose of study drug per day: 2.5 µg/day Study drug concentration: 25 µg/mL MT8 given 1 drop QID Udonitrectag: Eye drop solution in single dose unit. Vehicle: Eye drop solution with no active substance in single dose unit.	Dose 3 - 5 µg/Day Dose of study drug per day: 5 µg/day Study drug concentration: 50 µg/mL MT8 given 1 drop QID Udonitrectag: Eye drop solution in single dose unit. Vehicle: Eye drop solution with no active substance in single dose unit.	Vehicle Dose of study drug per day: 0 µg/day Study drug concentration: Vehicle given 1 drop QID Vehicle: Eye drop solution with no active substance in single dose unit.
Overall Study STARTED	27 27	26 26	26 26	29 29
Overall Study COMPLETED	23 23	21 21	21 21	23 23
Overall Study NOT COMPLETED	4 4	5 5	5 5	6 6

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

REC 0/0559 Eye Drops for Treatment of Moderate and Severe Neurotrophic Keratitis in Adult Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose 1 - 0.5 µg/Day n=27 Participants Dose of study drug per day: 0.5 µg/day Study drug concentration: 5 µg/mL MT8 given 1 drop QID Udonitrectag: Eye drop solution in single dose unit. Vehicle: Eye drop solution with no active substance in single dose unit.	Dose 2 - 2.5 µg/Day n=26 Participants Dose of study drug per day: 2.5 µg/day Study drug concentration: 25 µg/mL MT8 given 1 drop QID Udonitrectag: Eye drop solution in single dose unit. Vehicle: Eye drop solution with no active substance in single dose unit.	Dose 3 - 5 µg/Day n=26 Participants Dose of study drug per day: 5 µg/day Study drug concentration: 50 µg/mL MT8 given 1 drop QID Udonitrectag: Eye drop solution in single dose unit. Vehicle: Eye drop solution with no active substance in single dose unit.	Vehicle n=29 Participants Dose of study drug per day: 0 µg/day Study drug concentration: Vehicle given 1 drop QID Vehicle: Eye drop solution with no active substance in single dose unit.	Total n=108 Participants Total of all reporting groups
Age, Continuous	70.3 years STANDARD_DEVIATION 14.05 • n=93 Participants	59.6 years STANDARD_DEVIATION 15.30 • n=4 Participants	65.6 years STANDARD_DEVIATION 17.14 • n=27 Participants	67.0 years STANDARD_DEVIATION 16.76 • n=483 Participants	65.7 years STANDARD_DEVIATION 16.12 • n=36 Participants
Sex: Female, Male Female	13 Participants n=93 Participants	11 Participants n=4 Participants	14 Participants n=27 Participants	14 Participants n=483 Participants	52 Participants n=36 Participants
Sex: Female, Male Male	14 Participants n=93 Participants	15 Participants n=4 Participants	12 Participants n=27 Participants	15 Participants n=483 Participants	56 Participants n=36 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants	1 Participants n=36 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=93 Participants	4 Participants n=4 Participants	4 Participants n=27 Participants	5 Participants n=483 Participants	16 Participants n=36 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	24 Participants n=93 Participants	22 Participants n=4 Participants	22 Participants n=27 Participants	23 Participants n=483 Participants	91 Participants n=36 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	0 Participants n=4 Participants	3 Participants n=27 Participants	0 Participants n=483 Participants	3 Participants n=36 Participants
Race (NIH/OMB) White	26 Participants n=93 Participants	21 Participants n=4 Participants	19 Participants n=27 Participants	27 Participants n=483 Participants	93 Participants n=36 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	1 Participants n=36 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=93 Participants	4 Participants n=4 Participants	4 Participants n=27 Participants	2 Participants n=483 Participants	11 Participants n=36 Participants
Region of Enrollment Hungary	1 participants n=93 Participants	1 participants n=4 Participants	0 participants n=27 Participants	3 participants n=483 Participants	5 participants n=36 Participants
Region of Enrollment United States	3 participants n=93 Participants	4 participants n=4 Participants	4 participants n=27 Participants	6 participants n=483 Participants	17 participants n=36 Participants
Region of Enrollment Italy	13 participants n=93 Participants	6 participants n=4 Participants	6 participants n=27 Participants	7 participants n=483 Participants	32 participants n=36 Participants
Region of Enrollment United Kingdom	2 participants n=93 Participants	2 participants n=4 Participants	3 participants n=27 Participants	3 participants n=483 Participants	10 participants n=36 Participants
Region of Enrollment France	1 participants n=93 Participants	1 participants n=4 Participants	2 participants n=27 Participants	2 participants n=483 Participants	6 participants n=36 Participants
Region of Enrollment Germany	6 participants n=93 Participants	10 participants n=4 Participants	9 participants n=27 Participants	4 participants n=483 Participants	29 participants n=36 Participants
Region of Enrollment Spain	1 participants n=93 Participants	2 participants n=4 Participants	2 participants n=27 Participants	4 participants n=483 Participants	9 participants n=36 Participants
Height	166.694 cm STANDARD_DEVIATION 9.5229 • n=93 Participants	171.99 cm STANDARD_DEVIATION 9.5848 • n=4 Participants	169.598 cm STANDARD_DEVIATION 12.1409 • n=27 Participants	167.662 cm STANDARD_DEVIATION 14.8453 • n=483 Participants	168.748 cm STANDARD_DEVIATION 11.7409 • n=36 Participants
Weight	79.051 kg STANDARD_DEVIATION 19.1023 • n=93 Participants	77.379 kg STANDARD_DEVIATION 22.5637 • n=4 Participants	72.377 kg STANDARD_DEVIATION 14.5292 • n=27 Participants	74.718 kg STANDARD_DEVIATION 19.6181 • n=483 Participants	75.889 kg STANDARD_DEVIATION 19.0756 • n=36 Participants

PRIMARY outcome

Timeframe: At week 8

Population: The total patients were divided in subgroups according to disease stage (moderate or severe) and Region (EU or NA)

Outcome measures

Outcome measures
Measure	Dose 1 - 0.5 µg/Day n=27 Participants Dose of study drug per day: 0.5 µg/day Study drug concentration: 5 µg/mL MT8 given 1 drop QID Udonitrectag: Eye drop solution in single dose unit. Vehicle: Eye drop solution with no active substance in single dose unit.	Dose 2 - 2.5 µg/Day n=26 Participants Dose of study drug per day: 2.5 µg/day Study drug concentration: 25 µg/mL MT8 given 1 drop QID Udonitrectag: Eye drop solution in single dose unit. Vehicle: Eye drop solution with no active substance in single dose unit.	Dose 3 - 5 µg/Day n=26 Participants Dose of study drug per day: 5 µg/day Study drug concentration: 50 µg/mL MT8 given 1 drop QID Udonitrectag: Eye drop solution in single dose unit. Vehicle: Eye drop solution with no active substance in single dose unit.	Vehicle n=29 Participants Dose of study drug per day: 0 µg/day Study drug concentration: Vehicle given 1 drop QID Vehicle: Eye drop solution with no active substance in single dose unit.
Corneal Healing Disease stage 3 (Severe) EU · Not healed	11 Participants	9 Participants	9 Participants	7 Participants
Corneal Healing Disease stage 2 (moderate) NA · Not healed	0 Participants	2 Participants	2 Participants	3 Participants
Corneal Healing Disease stage 3 (Severe) NA · Healed	0 Participants	1 Participants	1 Participants	3 Participants
Corneal Healing Disease stage 3 (Severe) NA · Not healed	1 Participants	1 Participants	1 Participants	0 Participants
Corneal Healing Disease stage 2 (moderate) NA · Healed	2 Participants	0 Participants	0 Participants	0 Participants
Corneal Healing Disease stage 2 (moderate) EU · Healed	4 Participants	2 Participants	1 Participants	2 Participants
Corneal Healing Disease stage 2 (moderate) EU · Not healed	6 Participants	9 Participants	9 Participants	9 Participants
Corneal Healing Disease stage 3 (Severe) EU · Healed	3 Participants	2 Participants	3 Participants	5 Participants

SECONDARY outcome

Timeframe: At week 8

Population: The population was analysed in subgroups according to the location of the PED or corneal ulcer (central versus all locations).

Percentage of patients who achieve a 5-, 10-, and 15-letter mean improvement in best corrected distance visual acuity (BCDVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) chart at Week 8 compared to baseline (in all patients and in patients with a central location of the PED or corneal ulcer, respectively).

Outcome measures

Outcome measures
Measure	Dose 1 - 0.5 µg/Day n=27 Participants Dose of study drug per day: 0.5 µg/day Study drug concentration: 5 µg/mL MT8 given 1 drop QID Udonitrectag: Eye drop solution in single dose unit. Vehicle: Eye drop solution with no active substance in single dose unit.	Dose 2 - 2.5 µg/Day n=26 Participants Dose of study drug per day: 2.5 µg/day Study drug concentration: 25 µg/mL MT8 given 1 drop QID Udonitrectag: Eye drop solution in single dose unit. Vehicle: Eye drop solution with no active substance in single dose unit.	Dose 3 - 5 µg/Day n=26 Participants Dose of study drug per day: 5 µg/day Study drug concentration: 50 µg/mL MT8 given 1 drop QID Udonitrectag: Eye drop solution in single dose unit. Vehicle: Eye drop solution with no active substance in single dose unit.	Vehicle n=29 Participants Dose of study drug per day: 0 µg/day Study drug concentration: Vehicle given 1 drop QID Vehicle: Eye drop solution with no active substance in single dose unit.
Visual Acuity Improvement ≥ 10 letters (all locations) · Not improved	20 Participants	17 Participants	20 Participants	23 Participants
Visual Acuity Improvement ≥ 15 letters (all locations) · Improved	7 Participants	5 Participants	5 Participants	6 Participants
Visual Acuity Improvement ≥ 15 letters (all locations) · Not improved	20 Participants	21 Participants	21 Participants	23 Participants
Visual Acuity Improvement ≥ 5 letters (central PED or central corneal ulcer) · Improved	4 Participants	10 Participants	7 Participants	5 Participants
Visual Acuity Improvement ≥ 5 letters (central PED or central corneal ulcer) · Not improved	17 Participants	14 Participants	12 Participants	14 Participants
Visual Acuity Improvement ≥ 10 letters (central PED or central corneal ulcer) · Improved	3 Participants	8 Participants	5 Participants	4 Participants
Visual Acuity Improvement ≥ 10 letters (central PED or central corneal ulcer) · Not improved	18 Participants	16 Participants	14 Participants	15 Participants
Visual Acuity Improvement ≥ 15 letters (central PED or central corneal ulcer) · Improved	3 Participants	5 Participants	4 Participants	4 Participants
Visual Acuity Improvement ≥ 5 letters (all locations) · Improved	9 Participants	11 Participants	10 Participants	7 Participants
Visual Acuity Improvement ≥ 5 letters (all locations) · Not improved	18 Participants	15 Participants	16 Participants	22 Participants
Visual Acuity Improvement ≥ 10 letters (all locations) · Improved	7 Participants	9 Participants	6 Participants	6 Participants
Visual Acuity Improvement ≥ 15 letters (central PED or central corneal ulcer) · Not improved	18 Participants	19 Participants	15 Participants	15 Participants

Adverse Events

Dose 1 - 0.5 µg/Day

Serious events: 4 serious events

Other events: 18 other events

Deaths: 0 deaths

Dose 2 - 2.5 µg/Day

Serious events: 3 serious events

Other events: 17 other events

Deaths: 1 deaths

Dose 3 - 5 µg/Day

Serious events: 7 serious events

Other events: 18 other events

Deaths: 0 deaths

Vehicle

Serious events: 4 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Beatrice Martin, Clinical study Manager

Recordati Rare Diseases Sarl

Phone: +33 1 47 73 64 58

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Dose 1 - 0.5 µg/Day n=27 participants at risk Dose of study drug per day: 0.5 µg/day Study drug concentration: 5 µg/mL MT8 given 1 drop QID Udonitrectag: Eye drop solution in single dose unit. Vehicle: Eye drop solution with no active substance in single dose unit.	Dose 2 - 2.5 µg/Day n=26 participants at risk Dose of study drug per day: 2.5 µg/day Study drug concentration: 25 µg/mL MT8 given 1 drop QID Udonitrectag: Eye drop solution in single dose unit. Vehicle: Eye drop solution with no active substance in single dose unit.	Dose 3 - 5 µg/Day n=26 participants at risk Dose of study drug per day: 5 µg/day Study drug concentration: 50 µg/mL MT8 given 1 drop QID Udonitrectag: Eye drop solution in single dose unit. Vehicle: Eye drop solution with no active substance in single dose unit.	Vehicle n=29 participants at risk Dose of study drug per day: 0 µg/day Study drug concentration: Vehicle given 1 drop QID Vehicle: Eye drop solution with no active substance in single dose unit.
Eye disorders Ulcerative keratitis	3.7% 1/27 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	3.8% 1/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	11.5% 3/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	3.4% 1/29 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)
Eye disorders Corneal epithelium defect	3.7% 1/27 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/29 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)
Eye disorders Corneal erosion	0.00% 0/27 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	3.8% 1/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/29 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)
Eye disorders Corneal perforation	0.00% 0/27 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	3.8% 1/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/29 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)
Eye disorders Sudden visual loss	0.00% 0/27 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	3.4% 1/29 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)
Infections and infestations Herpes ophthalmic	0.00% 0/27 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	3.8% 1/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/29 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)
Infections and infestations Hypopyon	0.00% 0/27 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	3.8% 1/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/29 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)
Infections and infestations Ophthalmic herpes zoster	3.7% 1/27 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/29 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)
Infections and infestations Pneumonia	0.00% 0/27 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	3.8% 1/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	3.8% 1/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/29 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)
Infections and infestations Coronavirus infection	0.00% 0/27 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	3.8% 1/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/29 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)
Infections and infestations Postoperative wound infection	0.00% 0/27 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	3.4% 1/29 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)
Infections and infestations Sepsis	0.00% 0/27 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	3.8% 1/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/29 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)
Infections and infestations Wound sepsis	3.7% 1/27 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/29 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)
Cardiac disorders Myocardial infarction	0.00% 0/27 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	3.8% 1/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	3.4% 1/29 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)
Cardiac disorders Bradycardia	0.00% 0/27 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	3.4% 1/29 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)
Metabolism and nutrition disorders Dehydration	0.00% 0/27 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	3.4% 1/29 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)
Metabolism and nutrition disorders Iron deficiency	0.00% 0/27 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	3.4% 1/29 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)
Renal and urinary disorders Acute kidney injury	0.00% 0/27 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	3.8% 1/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/29 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)
Renal and urinary disorders Renal impairment	0.00% 0/27 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	3.4% 1/29 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	0.00% 0/27 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	3.8% 1/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/29 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)
Immune system disorders Corneal graft rejection	0.00% 0/27 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	3.8% 1/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/29 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/27 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	3.4% 1/29 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)
Nervous system disorders Intracranial pressure increased	3.7% 1/27 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/29 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)
Vascular disorders Hypertension	0.00% 0/27 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	0.00% 0/26 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)	3.4% 1/29 • Safety assessments were conducted for all patients from the Screening Visit (upon the signature of the ICF) to the end of the study (8 weeks)