Trial Outcomes & Findings for Safety and Efficacy Study on Cenegermin (Oxervate®) vs Vehicle in Severe Sjogren's Dry Eye Disease (PROTEGO-1 Study) (NCT NCT05133180)

Last Updated: 2024-06-07

Results Overview

The Schirmer test type I (without anaesthesia) was performed to measure aqueous tear secretion. The rounded bend end of a sterile strip was inserted into the lower conjunctival sac over the temporal one-third of the lower eyelid margin. After 5 minutes had elapsed, the Schirmer's test strip was removed and the length of the tear absorption on the strip was measured (millimeters/5 minutes). The longer the wetted length, the healthier the status of the eye.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

104 participants

Primary outcome timeframe

at week 4

Results posted on

2024-06-07

Participant Flow

A total of 126 patients ≥ 18 years with severe Sjögren's DE were assessed for eligibility. The enrolled patients (n=104) were randomized 1:1 in the study as follows: 52 patients to cenegermin and 52 to vehicle. A total of 5 patients discontinued the study prematurely: 2 patients from cenegermin group and 3 from vehicle. Regarding treatment discontinuation, a total of 5 patients discontinued the treatment prematurely: 3 patients from cenegermin and 2 from vehicle.

Participant milestones

Participant milestones
Measure	Oxervate One drop of cenegermin 20 mcg/mL (rhNGF 20 mcg/mL) in the pharmaceutical form of ophthalmic sterile solution was instilled in both eyes three times daily (TID), every six hours. Oxervate: Oxervate®, an ophthalmic solution containing cenegermin 20 mcg/mL, which is a recombinant human Nerve Growth Factor (rhNGF); one drop of the test product will be instilled in both eyes three times daily (TID).	Vehicle One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product
Overall Study STARTED	52	52
Overall Study Randomized But Not Treated	0	1
Overall Study Safety Population (SAF)	52	51
Overall Study Full Analysis Set Population (FAS)	52	51
Overall Study Per Protocol Population (PP)	46	47
Overall Study Prematurely Study Discontinued	2	3
Overall Study COMPLETED	50	49
Overall Study NOT COMPLETED	2	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Oxervate One drop of cenegermin 20 mcg/mL (rhNGF 20 mcg/mL) in the pharmaceutical form of ophthalmic sterile solution was instilled in both eyes three times daily (TID), every six hours. Oxervate: Oxervate®, an ophthalmic solution containing cenegermin 20 mcg/mL, which is a recombinant human Nerve Growth Factor (rhNGF); one drop of the test product will be instilled in both eyes three times daily (TID).	Vehicle One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product
Overall Study Withdrawal of consent	1	1
Overall Study Lost to Follow-up	1	1
Overall Study Documented disease progression	0	1

Baseline Characteristics

Safety and Efficacy Study on Cenegermin (Oxervate®) vs Vehicle in Severe Sjogren's Dry Eye Disease (PROTEGO-1 Study)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Oxervate (FAS) n=52 Participants One drop of cenegermin 20 mcg/mL (rhNGF 20 mcg/mL) in the pharmaceutical form of ophthalmic sterile solution was instilled in both eyes three times daily (TID), every six hours. Oxervate: Oxervate®, an ophthalmic solution containing cenegermin 20 mcg/mL, which is a recombinant human Nerve Growth Factor (rhNGF); one drop of the test product will be instilled in both eyes three times daily (TID).	Vehicle (FAS) n=51 Participants One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product	Total n=103 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Categorical Between 18 and 65 years	39 Participants n=99 Participants	34 Participants n=107 Participants	73 Participants n=206 Participants
Age, Categorical >=65 years	13 Participants n=99 Participants	17 Participants n=107 Participants	30 Participants n=206 Participants
Age, Continuous	55.3 years STANDARD_DEVIATION 13.47 • n=99 Participants	58.7 years STANDARD_DEVIATION 14.10 • n=107 Participants	57.0 years STANDARD_DEVIATION 13.83 • n=206 Participants
Sex: Female, Male Female	50 Participants n=99 Participants	47 Participants n=107 Participants	97 Participants n=206 Participants
Sex: Female, Male Male	2 Participants n=99 Participants	4 Participants n=107 Participants	6 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	3 Participants n=107 Participants	3 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) White	43 Participants n=99 Participants	39 Participants n=107 Participants	82 Participants n=206 Participants
Race (NIH/OMB) More than one race	1 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	8 Participants n=99 Participants	7 Participants n=107 Participants	15 Participants n=206 Participants
Region of Enrollment United States	25 participants n=99 Participants	28 participants n=107 Participants	53 participants n=206 Participants
Region of Enrollment Italy	27 participants n=99 Participants	23 participants n=107 Participants	50 participants n=206 Participants

PRIMARY outcome

Timeframe: at week 4

Population: The Full Analysis Set (FAS) population consisted of all patients who were randomized and received at least one dose of the investigational product. The number of participants effectively analyzed was 51 in Cenegermin group and 50 in the Vehicle group. In fact 1 patient in Cenegermin group and 1 patient in vehicle group had imputed values of missing data.

Outcome measures

Outcome measures
Measure	Oxervate (FAS) n=52 Participants One drop of cenegermin 20 mcg/mL (rhNGF 20 mcg/mL) in the pharmaceutical form of ophthalmic sterile solution was instilled in both eyes three times daily (TID), every six hours. Oxervate: Oxervate®, an ophthalmic solution containing cenegermin 20 mcg/mL, which is a recombinant human Nerve Growth Factor (rhNGF); one drop of the test product will be instilled in both eyes three times daily (TID).	Vehicle (FAS) n=51 Participants One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product
Number of Patients Reaching a Value of Schirmer I Test (Without Anaesthesia) >10mm/5min at Week 4	19 Participants	2 Participants

PRIMARY outcome

Timeframe: at week 12

Population: The Full Analysis Set (FAS) population consisted of all patients who were randomized and received at least one dose of the investigational product. Please note that adjusted means are reported.

The SANDE questionnaire is comprised of two questions: 1) How often do your eyes feel dry and/or irritated? And 2) How severe you feel your symptoms of dryness and/or irritation are? The SANDE questionnaire uses a 100 mm horizontal line for each question to assess the extent of patients' symptoms. In this questionnaire, frequency of symptoms ranges from "rarely" (0) to "all of the time" (100) and the severity of symptoms ranges from "very mild" (0) to "very severe" (100). At each visit, patients were asked to place a mark on the two given lines based on the extent of their symptoms. The locations of the marks made by the patients on the 100 mm horizontal lines were measured in mm from left to right. The global SANDE score is calculated by multiplying the frequency score by the severity score and obtaining the square root. Both for total score and for frequency or severity scores, 0 is the best condition, 100 the worst condition. Please note that adjusted means are reported.

Outcome measures

Outcome measures
Measure	Oxervate (FAS) n=52 Participants One drop of cenegermin 20 mcg/mL (rhNGF 20 mcg/mL) in the pharmaceutical form of ophthalmic sterile solution was instilled in both eyes three times daily (TID), every six hours. Oxervate: Oxervate®, an ophthalmic solution containing cenegermin 20 mcg/mL, which is a recombinant human Nerve Growth Factor (rhNGF); one drop of the test product will be instilled in both eyes three times daily (TID).	Vehicle (FAS) n=51 Participants One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product
Change From Baseline in Symptoms Questionnaire (SANDE) Global Score at Week 12	-29.5 score on a scale Interval -42.126 to -16.93	-25 score on a scale Interval -37.009 to -12.926

SECONDARY outcome

Timeframe: at Week 8

The Schirmer test type I (without anaesthesia) was performed to measure aqueous tear secretion. The rounded bend end of a sterile strip was inserted into the lower conjunctival sac over the temporal one-third of the lower eyelid margin. After 5 minutes had elapsed, the Schirmer's test strip was removed and the length of the tear absorption on the strip was measured (millimeters/5 minutes). The longer and the wetted length, the healthier the status of the eye.

Outcome measures

Outcome measures
Measure	Oxervate (FAS) n=52 Participants One drop of cenegermin 20 mcg/mL (rhNGF 20 mcg/mL) in the pharmaceutical form of ophthalmic sterile solution was instilled in both eyes three times daily (TID), every six hours. Oxervate: Oxervate®, an ophthalmic solution containing cenegermin 20 mcg/mL, which is a recombinant human Nerve Growth Factor (rhNGF); one drop of the test product will be instilled in both eyes three times daily (TID).	Vehicle (FAS) n=51 Participants One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product
Key Secondary Outcome: Number of Patients Reaching a Value of Schirmer I Test (Without Anaesthesia) > 10mm/5min at Week 8	18 Participants	2 Participants

SECONDARY outcome

Timeframe: At week 12

Population: The Full Analysis Set (FAS) population consisted of all patients who were randomized and received at least one dose of the investigational product. The number of participants effectively analyzed was 49 in Cenegermin group and 49 in the Vehicle group. In fact 3 patients in Cenegermin group and 2 patients in vehicle group had imputed values of missing data via a MI approach.

The SANDE questionnaire is comprised of two questions: 1) How often do your eyes feel dry and/or irritated? And 2) How severe you feel your symptoms of dryness and/or irritation are? This questionnaire uses a 100 mm horizontal line for each question to assess ocular discomfort and/or dryness experienced by the patients. In the SANDE questionnaire, frequency of symptoms ranges from "rarely" (0) to "all of the time" (100) and the severity of symptoms ranges from "very mild" (0) to "very severe" (100). At each visit, patients were asked to place a mark on the two given lines based on the extent of their symptoms. The locations of the marks made by the patients on the 100 mm horizontal lines were measured in mm from left to right and recorded. 0 was the best condition and 100 marked the worst condition. Global score from the SANDE questionnaire was calculated by multiplying the frequency score by the severity score and obtaining the square root. Means are adjusted means.

Outcome measures

Outcome measures
Measure	Oxervate (FAS) n=52 Participants One drop of cenegermin 20 mcg/mL (rhNGF 20 mcg/mL) in the pharmaceutical form of ophthalmic sterile solution was instilled in both eyes three times daily (TID), every six hours. Oxervate: Oxervate®, an ophthalmic solution containing cenegermin 20 mcg/mL, which is a recombinant human Nerve Growth Factor (rhNGF); one drop of the test product will be instilled in both eyes three times daily (TID).	Vehicle (FAS) n=51 Participants One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product
Key Secondary Outcome: Change From Baseline in Symptoms Assessment in Dry Eye (SANDE) Score for Frequency at Week 12	-24.546 score on a scale Interval -38.261 to -10.831	-21.793 score on a scale Interval -34.944 to -8.643

SECONDARY outcome

Timeframe: at Week 12

Population: The Full Analysis Set (FAS) population consisted of all patients who were randomized and received at least one dose of the investigational product. The number of participants effectively analyzed was 49 in Cenegermin group and 49 in the Vehicle group at Week 8 and Week 12, and 50 in Cenegermin group and 49 in Vehicle group at Week 16.

The SANDE questionnaire is comprised of two questions: 1) How often do your eyes feel dry and/or irritated? And 2) How severe you feel your symptoms of dryness and/or irritation are? This questionnaire uses a 100 mm horizontal line for each question to assess ocular discomfort and/or dryness experienced by the patients. In the SANDE questionnaire, frequency of symptoms ranges from "rarely" (0) to "all of the time" (100) and the severity of symptoms ranges from "very mild" (0) to "very severe" (100). At each visit, patients were asked to place a mark on the two given lines based on the extent of their symptoms. The locations of the marks made by the patients on the 100 mm horizontal lines were measured in mm from left to right and recorded. 0 was the best condition and 100 marked the worst condition. Global score from the SANDE questionnaire was calculated by multiplying the frequency score by the severity score and obtaining the square root. Means are adjusted means.

Outcome measures

Outcome measures
Measure	Oxervate (FAS) n=52 Participants One drop of cenegermin 20 mcg/mL (rhNGF 20 mcg/mL) in the pharmaceutical form of ophthalmic sterile solution was instilled in both eyes three times daily (TID), every six hours. Oxervate: Oxervate®, an ophthalmic solution containing cenegermin 20 mcg/mL, which is a recombinant human Nerve Growth Factor (rhNGF); one drop of the test product will be instilled in both eyes three times daily (TID).	Vehicle (FAS) n=51 Participants One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product
Key Secondary Outcome: Change From Baseline in Symptoms Assessment in Dry Eye (SANDE) Score for Severity at Week 12	-31.445 score on a scale Interval -43.795 to -19.095	-26.713 score on a scale Interval -38.538 to -14.887

SECONDARY outcome

Timeframe: At Weeks 12 and 4

Population: The Full Analysis Set (FAS) population consisted of all patients randomized, who received at least one dose of IP. 3 patients in Cenegermin group and 2 patients in vehicle group had imputed values of missing data for Impact on Daily Activities and Emotional Impact due to dry eye. For Impact on work due to dry eye the number of participants considered in the model was 30 in Cenegermin group and 34 in the Vehicle group, of which 4 and 6 had imputed values.

IDEEL is a 57-item questionnaire that assesses the impact of dry eye symptoms on everyday life. It is composed of 3 modules (Dry eye Quality of Life, Dry eye Treatment satisfaction \& Bother, Dry eye Symptom Bother). This outcome is about the first module: Quality of Life module (27 items) is composed by 3 dimensions: Dimension 1 - Impact on Daily Activities, calculated by mean of the non-missing item scores 1-6 multiplied by 20. (range 0-100) Dim. 2 - Emotional Impact: calculated by mean of the non-missing item scores 10-20 multiplied by 25. (range 0-100) Dim. 3 - Impact on Work: calculated by mean of the non-missing item scores 23-27 multiplied by 25. (range 0-100) Scores for each dimension of this module ranged from 0 to 100, where higher scores indicated less impact on daily activities, on work and on emotions. No combination of dimensions scores is done.

Outcome measures

Outcome measures
Measure	Oxervate (FAS) n=52 Participants One drop of cenegermin 20 mcg/mL (rhNGF 20 mcg/mL) in the pharmaceutical form of ophthalmic sterile solution was instilled in both eyes three times daily (TID), every six hours. Oxervate: Oxervate®, an ophthalmic solution containing cenegermin 20 mcg/mL, which is a recombinant human Nerve Growth Factor (rhNGF); one drop of the test product will be instilled in both eyes three times daily (TID).	Vehicle (FAS) n=51 Participants One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product
Key Secondary Outcome: Change From Baseline in Quality of Life Module Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 12 and at Week 4 Impact on daily activities - week 12	13.301 score on a scale Interval 6.267 to 20.335	9.223 score on a scale Interval 2.437 to 16.008
Key Secondary Outcome: Change From Baseline in Quality of Life Module Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 12 and at Week 4 Emotional impact due to dry eye - week 12	16.069 score on a scale Interval 7.476 to 24.661	10.519 score on a scale Interval 2.185 to 18.853
Key Secondary Outcome: Change From Baseline in Quality of Life Module Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 12 and at Week 4 Impact on work due to dry eye - week 12	18.619 score on a scale Interval 9.309 to 27.928	15.144 score on a scale Interval 6.371 to 23.916
Key Secondary Outcome: Change From Baseline in Quality of Life Module Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 12 and at Week 4 Impact on daily activities - week 4	11.524 score on a scale Interval 5.207 to 17.842	9.364 score on a scale Interval 3.354 to 15.374
Key Secondary Outcome: Change From Baseline in Quality of Life Module Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 12 and at Week 4 Emotional impact due to dry eye - week 4	14.385 score on a scale Interval 6.84 to 21.93	11.955 score on a scale Interval 4.732 to 19.177
Key Secondary Outcome: Change From Baseline in Quality of Life Module Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 12 and at Week 4 Impact on work due to dry eye - week 4	17.591 score on a scale Interval 8.213 to 26.969	14.291 score on a scale Interval 5.787 to 22.795

SECONDARY outcome

Timeframe: at Weeks 12 and 4

Population: The Full Analysis Set (FAS) population consisted of all patients who were randomized and received at least one dose of the investigational product. 3 patients in Cenegermin group and 4 patients in vehicle group had imputed values of missing data for Satisfaction with Treatment Effectiveness. For Treatment- Related Bother / Inconvenience, 4 patients in Cenegermin group and 3 patients in vehicle group had imputed values of missing data.

IDEEL is a 57-item questionnaire that assesses the impact of dry eye symptoms on everyday life. It is composed of 3 modules (Quality of Life, Treatment satisfaction \& Bother, Symptom Bother). This outcome is about the second module: Treatment Satisfaction \& Bother (8 items). This is composed by 2 dimensions: "Dim. 1" - Satisfaction with Treatment Effectiveness, calculated by mean of the non-missing item scores 2-5 multiplied by 25. (range 0-100) Dim. 2 - Treatment-Related Bother / Inconvenience calculated as the mean of the non-missing item scores 6, 8-10 multiplied by 25. (range 0-100) Scores for each dimension of this module range from 0 to 100, where higher scores indicate a greater satisfaction in treatment effectiveness and less treatment-related bother. No combination of dimension scores is done.

Outcome measures

Outcome measures
Measure	Oxervate (FAS) n=52 Participants One drop of cenegermin 20 mcg/mL (rhNGF 20 mcg/mL) in the pharmaceutical form of ophthalmic sterile solution was instilled in both eyes three times daily (TID), every six hours. Oxervate: Oxervate®, an ophthalmic solution containing cenegermin 20 mcg/mL, which is a recombinant human Nerve Growth Factor (rhNGF); one drop of the test product will be instilled in both eyes three times daily (TID).	Vehicle (FAS) n=51 Participants One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product
Key Secondary Outcome: Change From Baseline in "Treatment Satisfaction & Bother" Module Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Weeks 12 and 4 Satisfaction with Treatment Effectiveness - week 12	12.733 score on a scale Interval 1.18 to 24.285	16.938 score on a scale Interval 5.033 to 28.844
Key Secondary Outcome: Change From Baseline in "Treatment Satisfaction & Bother" Module Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Weeks 12 and 4 Treatment- Related Bother / Inconvenience - week 12	6.482 score on a scale Interval -0.877 to 13.842	4.239 score on a scale Interval -2.942 to 11.42
Key Secondary Outcome: Change From Baseline in "Treatment Satisfaction & Bother" Module Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Weeks 12 and 4 Satisfaction with Treatment Effectiveness - week 4	13.879 score on a scale Interval 2.071 to 25.686	14.428 score on a scale Interval 3.246 to 25.609
Key Secondary Outcome: Change From Baseline in "Treatment Satisfaction & Bother" Module Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Weeks 12 and 4 Treatment- Related Bother / Inconvenience - week 4	9.505 score on a scale Interval 2.772 to 16.237	8.432 score on a scale Interval 1.84 to 15.025

SECONDARY outcome

Timeframe: at Weeks 12 and 4

IDEEL is a 57-item questionnaire that assesses the impact of dry eye symptoms on everyday life. It is composed of 3 modules (Quality of Life, Treatment Satisfaction \& Bother, Symptom Bother). This outcome is about the third module: Symptom Bother (20 items). This is composed by 1 dimension: Dry Eye Symptom-Bother (range 0-100) The Symptom Bother score is calculated if at least 50% (10 items) of the 20 items within the dimension are completed, and non-missing; otherwise the score is set to missing. The Symptom Bother score is calculated as the mean of the non-missing item scores 1-20 multiplied by 25. The higher the score the greater the symptom bother.

Outcome measures

Outcome measures
Measure	Oxervate (FAS) n=52 Participants One drop of cenegermin 20 mcg/mL (rhNGF 20 mcg/mL) in the pharmaceutical form of ophthalmic sterile solution was instilled in both eyes three times daily (TID), every six hours. Oxervate: Oxervate®, an ophthalmic solution containing cenegermin 20 mcg/mL, which is a recombinant human Nerve Growth Factor (rhNGF); one drop of the test product will be instilled in both eyes three times daily (TID).	Vehicle (FAS) n=51 Participants One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product
Key Secondary Outcome: Change From Baseline in "Symptom Bother Module" Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Weeks 12 and 4 week 12	-16.323 score on a scale Interval -23.582 to -9.064	-7.533 score on a scale Interval -14.574 to -0.493
Key Secondary Outcome: Change From Baseline in "Symptom Bother Module" Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Weeks 12 and 4 week 4	-10.241 score on a scale Interval -16.924 to -3.557	-9.435 score on a scale Interval -15.876 to -2.995

SECONDARY outcome

Timeframe: At weeks 4, 8, 12

The examiner compared the overall appearance of the patient's corneal staining with a reference figure, simulating the pattern of staining encountered in dry eye disease. non attempt was made to count the dots or to assess the position or confluence of the dots. The examiner selected the appropriate grade that best represented the state of corneal staining intuitionally. The grading system recommended by NEI divides the cornea into five zones (central, superior, temporal, nasal, and inferior) and for each zone, the severity of the corneal staining is graded on a scale from 0 to 3 based on a reference figure. Therefore the maximum score (worst outcome) was 15, and the minimum (best outcome) was 0.

Outcome measures

Outcome measures
Measure	Oxervate (FAS) n=52 Participants One drop of cenegermin 20 mcg/mL (rhNGF 20 mcg/mL) in the pharmaceutical form of ophthalmic sterile solution was instilled in both eyes three times daily (TID), every six hours. Oxervate: Oxervate®, an ophthalmic solution containing cenegermin 20 mcg/mL, which is a recombinant human Nerve Growth Factor (rhNGF); one drop of the test product will be instilled in both eyes three times daily (TID).	Vehicle (FAS) n=51 Participants One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product
Key Secondary Outcome: Change From Baseline in Cornea and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) at Weeks 4, 8, 12 Week 4	-4.107 score on a scale Interval -5.723 to -2.49	-2.588 score on a scale Interval -4.118 to -1.059
Key Secondary Outcome: Change From Baseline in Cornea and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) at Weeks 4, 8, 12 Week 8	-4.442 score on a scale Interval -6.145 to -2.739	-2.668 score on a scale Interval -4.298 to -1.038
Key Secondary Outcome: Change From Baseline in Cornea and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) at Weeks 4, 8, 12 Week 12	-3.714 score on a scale Interval -5.522 to -1.905	-2.490 score on a scale Interval -4.222 to -0.758

SECONDARY outcome

Timeframe: At weeks 4, 8, 12

TFBUT was measured by determining the time to tear break-up.The TFBUT test was performed after instillation of 5 μl of 2% preservative free sodium fluorescein solution into the lower conjunctival sac of each eye. This measurement was performed within 10 seconds maximum. The TFBUT was measured twice during the first minute of instillation of the fluorescein. If the 2 readings differed by more than 2 sec., a third reading was taken. The TFBUT value was the average of the 2 or 3 measurements. Generally, a TFBUT value of 10-35 sec was considered normal. A value of less than 10 seconds may indicate tear film instability.

Outcome measures

Outcome measures
Measure	Oxervate (FAS) n=52 Participants One drop of cenegermin 20 mcg/mL (rhNGF 20 mcg/mL) in the pharmaceutical form of ophthalmic sterile solution was instilled in both eyes three times daily (TID), every six hours. Oxervate: Oxervate®, an ophthalmic solution containing cenegermin 20 mcg/mL, which is a recombinant human Nerve Growth Factor (rhNGF); one drop of the test product will be instilled in both eyes three times daily (TID).	Vehicle (FAS) n=51 Participants One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product
Key Secondary Outcome: Change From Baseline in Tear Film Break-Up Time (TFBUT) at Week 4, Week 8, Week 12 Week 4	1.808 seconds Interval 0.437 to 3.178	0.167 seconds Interval -1.144 to 1.479
Key Secondary Outcome: Change From Baseline in Tear Film Break-Up Time (TFBUT) at Week 4, Week 8, Week 12 Week 8	2.010 seconds Interval 0.579 to 3.441	0.876 seconds Interval -0.502 to 2.255
Key Secondary Outcome: Change From Baseline in Tear Film Break-Up Time (TFBUT) at Week 4, Week 8, Week 12 Week 12	1.973 seconds Interval 0.588 to 3.358	0.613 seconds Interval -0.715 to 1.941

SECONDARY outcome

Timeframe: Week 4, 8, 12 and 16

Population: The Full Analysis Set (FAS) population consisted of all patients who were randomized and received at least one dose of the investigational product. The actual number of participants effectively analyzed was 51 in the IMP group and 50 in the vehicle group at Week 4, 49 in both IMP and vehicle group at Week 8 and at Week 12, and 50 in the IMP group and 49 in the vehicle group at Week 16.

The Schirmer test type I (without anaesthesia) was performed to measure aqueous tear secretion. The rounded bend end of a sterile strip was inserted into the lower conjunctival sac over the temporal one-third of the lower eyelid margin. After 5 minutes had elapsed, the Schirmer's test strip was removed and the length of the tear absorption on the strip was measured (millimeters/5 minutes). The longer, the wetted length, the healthier the status of the eye.

Outcome measures

Outcome measures
Measure	Oxervate (FAS) n=52 Participants One drop of cenegermin 20 mcg/mL (rhNGF 20 mcg/mL) in the pharmaceutical form of ophthalmic sterile solution was instilled in both eyes three times daily (TID), every six hours. Oxervate: Oxervate®, an ophthalmic solution containing cenegermin 20 mcg/mL, which is a recombinant human Nerve Growth Factor (rhNGF); one drop of the test product will be instilled in both eyes three times daily (TID).	Vehicle (FAS) n=51 Participants One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product
Change From Baseline in Schirmer I Test (Without Anaesthesia) [Time Frame: Week 4, 8, 12 and 16]. week 4	5.4 millimeters Standard Deviation 6.6	0.8 millimeters Standard Deviation 2.7
Change From Baseline in Schirmer I Test (Without Anaesthesia) [Time Frame: Week 4, 8, 12 and 16]. week 8	4.9 millimeters Standard Deviation 6.6	1.4 millimeters Standard Deviation 2.9
Change From Baseline in Schirmer I Test (Without Anaesthesia) [Time Frame: Week 4, 8, 12 and 16]. week 12	3.8 millimeters Standard Deviation 5.2	1.4 millimeters Standard Deviation 4.1
Change From Baseline in Schirmer I Test (Without Anaesthesia) [Time Frame: Week 4, 8, 12 and 16]. week 16	3.6 millimeters Standard Deviation 5.1	1.7 millimeters Standard Deviation 4.8

SECONDARY outcome

Timeframe: at Week 16

Population: The Full Analysis Set (FAS) population consisted of all patients who were randomized and received at least one dose of the investigational product. The number of participants effectively analyzed at weeks 8 and 12 was 49 in Cenegermin group and 49 in the Vehicle group. At week 4 the participants analyzed were 51 in Cenegermin and 50 in Vehicle group. At week 16, the number of participants analyzed were 50 in Cenegermin and 49 in Vehicle group.

Outcome measures

Outcome measures
Measure	Oxervate (FAS) n=50 Participants One drop of cenegermin 20 mcg/mL (rhNGF 20 mcg/mL) in the pharmaceutical form of ophthalmic sterile solution was instilled in both eyes three times daily (TID), every six hours. Oxervate: Oxervate®, an ophthalmic solution containing cenegermin 20 mcg/mL, which is a recombinant human Nerve Growth Factor (rhNGF); one drop of the test product will be instilled in both eyes three times daily (TID).	Vehicle (FAS) n=49 Participants One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product
Change From Baseline in Cornea and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) at Week 16	-3.3 score on a scale Standard Deviation 4.6	-2.7 score on a scale Standard Deviation 5.8

SECONDARY outcome

Timeframe: at week 16

Population: The Full Analysis Set (FAS) population consisted of all patients who were randomized and received at least one dose of the investigational product. he number of participants effectively analyzed at weeks 8 and 12 was 49 in Cenegermin group and 49 at the Vehicle group. At week 4 the participants analyzed were 51 in Cenegermin and 50 in Vehicle group. At week 16, the number of participants analyzed were 50 in Cenegermin group and 49 in the Vehicle group.

Outcome measures

Outcome measures
Measure	Oxervate (FAS) n=50 Participants One drop of cenegermin 20 mcg/mL (rhNGF 20 mcg/mL) in the pharmaceutical form of ophthalmic sterile solution was instilled in both eyes three times daily (TID), every six hours. Oxervate: Oxervate®, an ophthalmic solution containing cenegermin 20 mcg/mL, which is a recombinant human Nerve Growth Factor (rhNGF); one drop of the test product will be instilled in both eyes three times daily (TID).	Vehicle (FAS) n=49 Participants One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product
Change From Baseline in Tear Film Break-Up Time (TFBUT) at Week 16	1.3 seconds Standard Deviation 3.1	0.4 seconds Standard Deviation 2.8

SECONDARY outcome

Timeframe: at Week 8, Week 12, Week 16

Population: The Full Analysis Set (FAS) population consisted of all patients who were randomized and received at least one dose of the investigational product. The number of participants effectively analyzed was 49 in Cenegermin group and 49 in the Vehicle group at Week 8 and Week 12, and 50 in Cenegermin group and 49 in Vehicle group at Week 16.

The SANDE questionnaire is comprised of two questions: 1) How often do your eyes feel dry and/or irritated? And 2) How severe you feel your symptoms of dryness and/or irritation are? This questionnaire uses a 100 mm horizontal line for each question to assess ocular discomfort and/or dryness experienced by the patients. In the SANDE questionnaire, frequency of symptoms ranges from "rarely" (0) to "all of the time" (100) and the severity of symptoms ranges from "very mild" (0) to "very severe" (100). At each visit, patients were asked to place a mark on the two given lines based on the extent of their symptoms. The locations of the marks made by the patients on the 100 mm horizontal lines were measured in mm from left to right and recorded. 0 was the best condition and 100 marked the worst condition. Global score from the SANDE questionnaire was calculated by multiplying the frequency score by the severity score and obtaining the square root.

Outcome measures

Outcome measures
Measure	Oxervate (FAS) n=52 Participants One drop of cenegermin 20 mcg/mL (rhNGF 20 mcg/mL) in the pharmaceutical form of ophthalmic sterile solution was instilled in both eyes three times daily (TID), every six hours. Oxervate: Oxervate®, an ophthalmic solution containing cenegermin 20 mcg/mL, which is a recombinant human Nerve Growth Factor (rhNGF); one drop of the test product will be instilled in both eyes three times daily (TID).	Vehicle (FAS) n=51 Participants One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product
Change From Baseline in Symptoms Questionnaire (SANDE) Global Score at Week 8, Week 12, Week 16 week 8	-26.0 score on a scale Standard Deviation 20.1	-15.2 score on a scale Standard Deviation 22.1
Change From Baseline in Symptoms Questionnaire (SANDE) Global Score at Week 8, Week 12, Week 16 week 12	-20.4 score on a scale Standard Deviation 22.0	-15.7 score on a scale Standard Deviation 26.7
Change From Baseline in Symptoms Questionnaire (SANDE) Global Score at Week 8, Week 12, Week 16 week 16	-15.2 score on a scale Standard Deviation 20.5	-16.0 score on a scale Standard Deviation 25.2

SECONDARY outcome

Timeframe: at Week 8, Week 12, Week 16

Population: The Full Analysis Set (FAS) population consisted of all patients who were randomized and received at least one dose of the investigational product. The number of participants effectively analyzed was 49 in Cenegermin group and 49 in the Vehicle group at Week 8 and Week 12, and 50 in Cenegermin group and 49 in Vehicle group at Week 16

The SANDE questionnaire is comprised of two questions: 1) How often do your eyes feel dry and/or irritated? And 2) How severe you feel your symptoms of dryness and/or irritation are? This questionnaire uses a 100 mm horizontal line for each question to assess ocular discomfort and/or dryness experienced by the patients. In the SANDE questionnaire, frequency of symptoms ranges from "rarely" (0) to "all of the time" (100) and the severity of symptoms ranges from "very mild" (0) to "very severe" (100). At each visit, patients were asked to place a mark on the two given lines based on the extent of their symptoms. The locations of the marks made by the patients on the 100 mm horizontal lines were measured in mm from left to right and recorded. 0 was the best condition and 100 marked the worst condition. Global score from the SANDE questionnaire was calculated by multiplying the frequency score by the severity score and obtaining the square root.

Outcome measures

Outcome measures
Measure	Oxervate (FAS) n=52 Participants One drop of cenegermin 20 mcg/mL (rhNGF 20 mcg/mL) in the pharmaceutical form of ophthalmic sterile solution was instilled in both eyes three times daily (TID), every six hours. Oxervate: Oxervate®, an ophthalmic solution containing cenegermin 20 mcg/mL, which is a recombinant human Nerve Growth Factor (rhNGF); one drop of the test product will be instilled in both eyes three times daily (TID).	Vehicle (FAS) n=51 Participants One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product
Change From Baseline in Symptoms Questionnaire (SANDE) Score for Frequency at Week 8, Week 12, Week 16 week 8	-27.1 score on a scale Standard Deviation 22.5	-15.9 score on a scale Standard Deviation 24.4
Change From Baseline in Symptoms Questionnaire (SANDE) Score for Frequency at Week 8, Week 12, Week 16 week 12	-17.9 score on a scale Standard Deviation 23.4	-15.7 score on a scale Standard Deviation 28.2
Change From Baseline in Symptoms Questionnaire (SANDE) Score for Frequency at Week 8, Week 12, Week 16 week 16	-12.5 score on a scale Standard Deviation 21.2	-16.1 score on a scale Standard Deviation 25.6

SECONDARY outcome

Timeframe: at Week 8, week 12 and week 16

Population: The Full Analysis Set (FAS) population consisted of all patients who were randomized and received at least one dose of the investigational product. The number of participants effectively analyzed was 49 in Cenegermin group and 49 in the Vehicle group at Week 8 and Week 12, and 50 in Cenegermin group and 49 in Vehicle group at Week 16

The SANDE questionnaire is comprised of two questions: 1) How often do your eyes feel dry and/or irritated? And 2) How severe you feel your symptoms of dryness and/or irritation are? This questionnaire uses a 100 mm horizontal line for each question to assess ocular discomfort and/or dryness experienced by the patients. In the SANDE questionnaire, frequency of symptoms ranges from "rarely" (0) to "all of the time" (100) and the severity of symptoms ranges from "very mild" (0) to "very severe" (100). At each visit, patients were asked to place a mark on the two given lines based on the extent of their symptoms. The locations of the marks made by the patients on the 100 mm horizontal lines were measured in mm from left to right and recorded. 0 was the best condition and 100 marked the worst condition. Global score from the SANDE questionnaire was calculated by multiplying the frequency score by the severity score and obtaining the square root.

Outcome measures

Outcome measures
Measure	Oxervate (FAS) n=52 Participants One drop of cenegermin 20 mcg/mL (rhNGF 20 mcg/mL) in the pharmaceutical form of ophthalmic sterile solution was instilled in both eyes three times daily (TID), every six hours. Oxervate: Oxervate®, an ophthalmic solution containing cenegermin 20 mcg/mL, which is a recombinant human Nerve Growth Factor (rhNGF); one drop of the test product will be instilled in both eyes three times daily (TID).	Vehicle (FAS) n=51 Participants One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product
Change From Baseline in Symptoms Assessment in Dry Eye (SANDE) Score for Severity at Week 8, Week 12 and Week 16 week 8	-23.7 score on a scale Standard Deviation 20.8	-14.4 score on a scale Standard Deviation 21.6
Change From Baseline in Symptoms Assessment in Dry Eye (SANDE) Score for Severity at Week 8, Week 12 and Week 16 week 12	-21.2 score on a scale Standard Deviation 23.5	-15.7 score on a scale Standard Deviation 26.5
Change From Baseline in Symptoms Assessment in Dry Eye (SANDE) Score for Severity at Week 8, Week 12 and Week 16 week 16	-16.6 score on a scale Standard Deviation 23.6	-16.1 score on a scale Standard Deviation 25.9

SECONDARY outcome

Timeframe: at week 4

Population: The Full Analysis Set (FAS) population consisted of all patients who were randomized and received at least one dose of the investigational product.

Symptoms Scores (SANDE) and/or NEI Score were punctually described in the previous outcome descriptions. For Sande score, the scale ranges from 0 to 100 for both severity and frequency, where 0 was the best condition and 100 marked the worst condition. Hence the higher the score, the worse the outcome. For NEI score, the maximum score (worst outcome) was 15, and the minimum (best outcome) was 0; hence the higher the score, the worse the outcome.

Outcome measures

Outcome measures
Measure	Oxervate (FAS) n=52 Participants One drop of cenegermin 20 mcg/mL (rhNGF 20 mcg/mL) in the pharmaceutical form of ophthalmic sterile solution was instilled in both eyes three times daily (TID), every six hours. Oxervate: Oxervate®, an ophthalmic solution containing cenegermin 20 mcg/mL, which is a recombinant human Nerve Growth Factor (rhNGF); one drop of the test product will be instilled in both eyes three times daily (TID).	Vehicle (FAS) n=51 Participants One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product
Number of Patients Who Experienced a Worsening in Symptoms Scores (SANDE) and/or NEI Score > = 50% at Week 4	4 Participants	11 Participants

SECONDARY outcome

Timeframe: At weeks 8 and 16

Population: The Full Analysis Set (FAS) consisted of all patients randomized and dosed with at least one dose of the IP. The # of pts actually analyzed for Impact on Daily Activities and Emotional Impact due to Dry Eye was: Week 4: n=51 Cenegermin (C) n=50 Vehicle (V); Weeks 8 and 12: n=49 in both groups Week 16: n=50 C n=49 V. For Impact on work due to dry eye the No of pts actually analyzed was: Weeks 4 and 8 n= 24 C n= 30 V Week 12 n=23 C n=28 V Week 16: n= 23 C n=29 V

Outcome measures

Outcome measures
Measure	Oxervate (FAS) n=52 Participants One drop of cenegermin 20 mcg/mL (rhNGF 20 mcg/mL) in the pharmaceutical form of ophthalmic sterile solution was instilled in both eyes three times daily (TID), every six hours. Oxervate: Oxervate®, an ophthalmic solution containing cenegermin 20 mcg/mL, which is a recombinant human Nerve Growth Factor (rhNGF); one drop of the test product will be instilled in both eyes three times daily (TID).	Vehicle (FAS) n=51 Participants One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product
Change From Baseline in Quality of Life Module Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Weeks 8 and 16 Impact on Daily Activities - week 8	14.6 score on a scale Standard Deviation 18.8	6.5 score on a scale Standard Deviation 23.2
Change From Baseline in Quality of Life Module Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Weeks 8 and 16 Emotional Impact due to Dry Eye - week 8	18.4 score on a scale Standard Deviation 21.9	10.3 score on a scale Standard Deviation 22.9
Change From Baseline in Quality of Life Module Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Weeks 8 and 16 Impact on Work due to Dry Eye - week 8	17.7 score on a scale Standard Deviation 25.7	9.5 score on a scale Standard Deviation 25.9
Change From Baseline in Quality of Life Module Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Weeks 8 and 16 Impact on Daily Activities - week 16	15.1 score on a scale Standard Deviation 20.8	9.7 score on a scale Standard Deviation 21.1
Change From Baseline in Quality of Life Module Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Weeks 8 and 16 Emotional Impact due to Dry Eye - week 16	19.0 score on a scale Standard Deviation 23.1	11.5 score on a scale Standard Deviation 23.3
Change From Baseline in Quality of Life Module Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Weeks 8 and 16 Impact on Work due to Dry Eye - week 16	20.9 score on a scale Standard Deviation 24.2	9.3 score on a scale Standard Deviation 26.7

SECONDARY outcome

Timeframe: at Week 8 and Week 16

Population: The Full Analysis Set (FAS) population consisted of all patients who were randomized and received at least one dose of the investigational product. The number of participants effectively analyzed was 51 in Cenegermin group and 50 in the Vehicle group at Week 4, 49 in both treatment groups at Week 8 and Week 12, 50 in Cenegermin group and 49 in Vehicle group at Week 16.

Outcome measures

Outcome measures
Measure	Oxervate (FAS) n=52 Participants One drop of cenegermin 20 mcg/mL (rhNGF 20 mcg/mL) in the pharmaceutical form of ophthalmic sterile solution was instilled in both eyes three times daily (TID), every six hours. Oxervate: Oxervate®, an ophthalmic solution containing cenegermin 20 mcg/mL, which is a recombinant human Nerve Growth Factor (rhNGF); one drop of the test product will be instilled in both eyes three times daily (TID).	Vehicle (FAS) n=51 Participants One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product
Change From Baseline in "Symptom Bother Module" Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 8 and Week 16 week 8	-19.5 score on a scale Standard Deviation 20.3	-6.9 score on a scale Standard Deviation 19.2
Change From Baseline in "Symptom Bother Module" Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 8 and Week 16 week 16	-18.6 score on a scale Standard Deviation 19.4	-11.1 score on a scale Standard Deviation 22.3

SECONDARY outcome

Timeframe: at Week 8 and Week 16

Population: The FAS consisted of all patients randomized and dosed with at least one dose of the IP. The # of pts effectively analyzed for Impact on Daily Activities and Emotional Impact due to Dry Eye was: for Satisfaction with Treatment Effectiveness section: Wk 4: n=48 C n=44 V; Wk 8: n=47 C n=44 V Wk 12 n=48 C n=44 V Wk 16: n=48 C n=42 V. For T-Related Bother / Inconvenience section: Wk 4 n= 48 C n= 44 V Wk 8: n=46 both groups Wk 12 n=47 C n=46 V Wk 16: n= 48 C n=46 V

IDEEL is a 57-item questionnaire that assesses the impact of dry eye symptoms on everyday life. It is composed of 3 modules (Quality of Life, Treatment satisfaction \& Bother, Symptom Bother). This outcome is about the second module: Treatment Satisfaction \& Bother (8 items). This is composed by 2 dimensions: Dim. 1 - Satisfaction with Treatment Effectiveness, calculated by mean of the non-missing item scores 2-5 multiplied by 25. (range 0-100) Dim. 2 - Treatment-Related Bother / Inconvenience calculated as the mean of the non-missing item scores 6, 8-10 multiplied by 25. (range 0-100) Scores for each dimension of this module range from 0 to 100, where higher scores indicate a greater satisfaction in treatment effectiveness and less treatment-related bother. No combination of dimension scores is done.

Outcome measures

Outcome measures
Measure	Oxervate (FAS) n=52 Participants One drop of cenegermin 20 mcg/mL (rhNGF 20 mcg/mL) in the pharmaceutical form of ophthalmic sterile solution was instilled in both eyes three times daily (TID), every six hours. Oxervate: Oxervate®, an ophthalmic solution containing cenegermin 20 mcg/mL, which is a recombinant human Nerve Growth Factor (rhNGF); one drop of the test product will be instilled in both eyes three times daily (TID).	Vehicle (FAS) n=51 Participants One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product
Change From Baseline in "Treatment Satisfaction & Bother" Module Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 8 and Week 16 Satisfaction with Treatment Effectiveness - week 8	17.7 score on a scale Standard Deviation 31.0	7.7 score on a scale Standard Deviation 36.4
Change From Baseline in "Treatment Satisfaction & Bother" Module Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 8 and Week 16 Satisfaction with Treatment Effectiveness - week 16	13.4 score on a scale Standard Deviation 28.7	1.2 score on a scale Standard Deviation 35.9
Change From Baseline in "Treatment Satisfaction & Bother" Module Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 8 and Week 16 Treatment- Related Bother / Inconvenience - week 16	13.3 score on a scale Standard Deviation 23.6	5.3 score on a scale Standard Deviation 27.3
Change From Baseline in "Treatment Satisfaction & Bother" Module Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 8 and Week 16 Treatment- Related Bother / Inconvenience - week 8	16.6 score on a scale Standard Deviation 21.1	2.7 score on a scale Standard Deviation 28.1

OTHER_PRE_SPECIFIED outcome

Timeframe: From Screening to Visit 7 (follow-up, week 24)

Population: The SAF population consisted of all randomized patients who received at least one dose of the investigational product. SAF set was analysed according to the actual treatment received. The SAF population was used to present results on safety data.

TEAE=any AE started on or after the date of the first dose of study medication or started prior to first dose and worsened in severity after the first dose.

Outcome measures

Outcome measures
Measure	Oxervate (FAS) n=52 Participants One drop of cenegermin 20 mcg/mL (rhNGF 20 mcg/mL) in the pharmaceutical form of ophthalmic sterile solution was instilled in both eyes three times daily (TID), every six hours. Oxervate: Oxervate®, an ophthalmic solution containing cenegermin 20 mcg/mL, which is a recombinant human Nerve Growth Factor (rhNGF); one drop of the test product will be instilled in both eyes three times daily (TID).	Vehicle (FAS) n=51 Participants One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product
Incidence and Frequency of TEAEs, Assessed Throughout the Study. Severe TEAE - Non Opthalmic	2 Participants	1 Participants
Incidence and Frequency of TEAEs, Assessed Throughout the Study. Serious TEAE - Ophtalmic	1 Participants	0 Participants
Incidence and Frequency of TEAEs, Assessed Throughout the Study. Serious TEAE - Non Ophtalmic	2 Participants	1 Participants
Incidence and Frequency of TEAEs, Assessed Throughout the Study. TEAE - Ophtalmic	35 Participants	13 Participants
Incidence and Frequency of TEAEs, Assessed Throughout the Study. TEAE - Non Ophtalmic	16 Participants	9 Participants
Incidence and Frequency of TEAEs, Assessed Throughout the Study. Severe TEAE - Ophtamic	5 Participants	1 Participants
Incidence and Frequency of TEAEs, Assessed Throughout the Study. non-serious TEAE	37 Participants	15 Participants
Incidence and Frequency of TEAEs, Assessed Throughout the Study. Adverse Drug Reaction (ADR) - Ophtalmic	34 Participants	8 Participants
Incidence and Frequency of TEAEs, Assessed Throughout the Study. Adverse Drug Reaction - Non Ophtalmic	4 Participants	2 Participants
Incidence and Frequency of TEAEs, Assessed Throughout the Study. Serious ADR	1 Participants	0 Participants
Incidence and Frequency of TEAEs, Assessed Throughout the Study. TEAE leading to IMP discontinuation	2 Participants	1 Participants
Incidence and Frequency of TEAEs, Assessed Throughout the Study. TEAE leading to study discontinuation	0 Participants	1 Participants
Incidence and Frequency of TEAEs, Assessed Throughout the Study. TEAE leading to death	0 Participants	0 Participants

Adverse Events

Oxervate (SAF)

Serious events: 2 serious events

Other events: 37 other events

Deaths: 0 deaths

Vehicle (SAF)

Serious events: 1 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Oxervate (SAF) n=52 participants at risk One drop of cenegermin 20 mcg/mL (rhNGF 20 mcg/mL) in the pharmaceutical form of ophthalmic sterile solution was instilled in both eyes three times daily (TID), every six hours. Oxervate: Oxervate®, an ophthalmic solution containing cenegermin 20 mcg/mL, which is a recombinant human Nerve Growth Factor (rhNGF); one drop of the test product will be instilled in both eyes three times daily (TID).	Vehicle (SAF) n=51 participants at risk One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product
Eye disorders Visual acuity reduced	1.9% 1/52 • Number of events 1 • Adverse events were collected from screening visit (Day -8) to follow up (Day 168+/- 7 days) Adverse Event (AE) was defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.	0.00% 0/51 • Adverse events were collected from screening visit (Day -8) to follow up (Day 168+/- 7 days) Adverse Event (AE) was defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Gastrointestinal disorders Pancreatitis acute	1.9% 1/52 • Number of events 1 • Adverse events were collected from screening visit (Day -8) to follow up (Day 168+/- 7 days) Adverse Event (AE) was defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.	0.00% 0/51 • Adverse events were collected from screening visit (Day -8) to follow up (Day 168+/- 7 days) Adverse Event (AE) was defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Hepatobiliary disorders Hypertransaminasaemia	1.9% 1/52 • Number of events 1 • Adverse events were collected from screening visit (Day -8) to follow up (Day 168+/- 7 days) Adverse Event (AE) was defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.	0.00% 0/51 • Adverse events were collected from screening visit (Day -8) to follow up (Day 168+/- 7 days) Adverse Event (AE) was defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Infections and infestations Bacteraemia	1.9% 1/52 • Number of events 1 • Adverse events were collected from screening visit (Day -8) to follow up (Day 168+/- 7 days) Adverse Event (AE) was defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.	0.00% 0/51 • Adverse events were collected from screening visit (Day -8) to follow up (Day 168+/- 7 days) Adverse Event (AE) was defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Musculoskeletal and connective tissue disorders Arthropathy	0.00% 0/52 • Adverse events were collected from screening visit (Day -8) to follow up (Day 168+/- 7 days) Adverse Event (AE) was defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.	2.0% 1/51 • Number of events 1 • Adverse events were collected from screening visit (Day -8) to follow up (Day 168+/- 7 days) Adverse Event (AE) was defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.

Other adverse events

Additional Information

Clinical Development & Operations

Dompé farmaceutici SpA

Phone: +39 02 583831

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place