Trial Outcomes & Findings for Study to Evaluate Safety and Efficacy of Cenegermin (Oxervate®) vs Vehicle in Severe Sjogren's Dry Eye Disease (NCT NCT05136170)

Last Updated: 2025-11-26

Results Overview

The Schirmer test was used in ophthalmic examination to measure tear production for the diagnosis of conditions such as keratoconjunctivitis sicca and dry eye. Without previously instilling anesthetic drops, the Schirmer strip was inserted into the lower conjunctival sac at the junction of the lateral and middle thirds, avoiding touching the cornea, and the length of wetting strips in millimeters was recorded after 5 minutes. 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). Cutoff values: \<5 mm - pathologic dry eye 5-10 mm - marginal dry eye \>10 and \<30 mm - normal secretion The longer, the wetted length, the healthier the status of the eye. No units other than participants were assigned.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

85 participants

Primary outcome timeframe

At Week 4 (Visit 3)

Results posted on

2025-11-26

Participant Flow

Three sites in Italy out of the four opened, and 7 sites in US enrolled patients. A total of 97 adult patients (≥ 18 years) with a diagnosis of severe Sjögren's DED was assessed for eligibility. There were 12 screening failures. The remaining patients (n=85) were randomized 1:1 as follows: 44 to cenegermin and 41 to vehicle. One patient in the vehicle group did not receive study medication and was excluded from the SAF and FAS.

No units other than participants were assigned.

Participant milestones

Participant milestones
Measure	Cenegermin Oxervate®, an ophthalmic solution containing cenegermin 20 mcg/mL, which is a recombinant human Nerve Growth Factor (rhNGF). In this arm one drop of cenegermin 20 mcg/mL was instilled in both eyes TID for 28 consecutive days. Cenegermin: One drop of the test product was instilled in both eyes TID	Vehicle In this arm one drop of vehicle was a instilled in both eyes TID for 28 consecutive days. Vehicle: One drop of the placebo was instilled in both eyes TID
Overall Study STARTED	44	41
Overall Study Randomized But Not Treated	0	1
Overall Study Safety Population (SAF)	44	40
Overall Study Full Analysis Set Population (FAS)	44	40
Overall Study Per Protocol Set (PP)	38	33
Overall Study COMPLETED	41	39
Overall Study NOT COMPLETED	3	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Cenegermin Oxervate®, an ophthalmic solution containing cenegermin 20 mcg/mL, which is a recombinant human Nerve Growth Factor (rhNGF). In this arm one drop of cenegermin 20 mcg/mL was instilled in both eyes TID for 28 consecutive days. Cenegermin: One drop of the test product was instilled in both eyes TID	Vehicle In this arm one drop of vehicle was a instilled in both eyes TID for 28 consecutive days. Vehicle: One drop of the placebo was instilled in both eyes TID
Overall Study Withdrawal by Subject	2	2
Overall Study Can no longer make office visits	1	0

Baseline Characteristics

Study to Evaluate Safety and Efficacy of Cenegermin (Oxervate®) vs Vehicle in Severe Sjogren's Dry Eye Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cenegermin - FAS n=44 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. Cenegermin: 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=40 Participants In this arm one drop of vehicle was instilled in both eyes TID for 28 consecutive days. Vehicle: Vehicle was instilled with the same scheme of the test product	Total n=84 Participants Total of all reporting groups
Race (NIH/OMB) White	37 Participants n=492 Participants	30 Participants n=492 Participants	67 Participants n=984 Participants
Race (NIH/OMB) More than one race	0 Participants n=492 Participants	0 Participants n=492 Participants	0 Participants n=984 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=492 Participants	2 Participants n=492 Participants	5 Participants n=984 Participants
Region of Enrollment United States	21 participants n=492 Participants	21 participants n=492 Participants	42 participants n=984 Participants
Region of Enrollment Italy	23 participants n=492 Participants	19 participants n=492 Participants	42 participants n=984 Participants
Age, Categorical <=18 years	0 Participants n=492 Participants	0 Participants n=492 Participants	0 Participants n=984 Participants
Age, Categorical Between 18 and 65 years	35 Participants n=492 Participants	27 Participants n=492 Participants	62 Participants n=984 Participants
Age, Categorical >=65 years	9 Participants n=492 Participants	13 Participants n=492 Participants	22 Participants n=984 Participants
Age, Continuous	55.0 years STANDARD_DEVIATION 13.93 • n=492 Participants	58.1 years STANDARD_DEVIATION 12.84 • n=492 Participants	56.5 years STANDARD_DEVIATION 13.43 • n=984 Participants
Sex: Female, Male Female	38 Participants n=492 Participants	35 Participants n=492 Participants	73 Participants n=984 Participants
Sex: Female, Male Male	6 Participants n=492 Participants	5 Participants n=492 Participants	11 Participants n=984 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=492 Participants	2 Participants n=492 Participants	5 Participants n=984 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	41 Participants n=492 Participants	38 Participants n=492 Participants	79 Participants n=984 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=492 Participants	0 Participants n=492 Participants	0 Participants n=984 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=492 Participants	0 Participants n=492 Participants	0 Participants n=984 Participants
Race (NIH/OMB) Asian	0 Participants n=492 Participants	4 Participants n=492 Participants	4 Participants n=984 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=492 Participants	0 Participants n=492 Participants	0 Participants n=984 Participants
Race (NIH/OMB) Black or African American	4 Participants n=492 Participants	4 Participants n=492 Participants	8 Participants n=984 Participants

PRIMARY outcome

Timeframe: At Week 4 (Visit 3)

Population: Full Analysis set The FAS population consisted of all randomized patients who received at least one dose of the investigational product. The FAS population was used for the primary analysis of the study and to present results on efficacy data. While at baseline FAS patients were n=44 for IMP and 40 for Vehicle, at week 4 patients analyzed were n=43 in the IMP group and n=39 in the Vehicle arm.

Outcome measures

Outcome measures
Measure	Cenegermin - FAS n=43 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. Cenegermin: 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=39 Participants In this arm one drop of vehicle was instilled in both eyes TID for 28 consecutive days. Vehicle: Vehicle was instilled with the same scheme of the test product
Number of Patients With Schirmer I Test (Without Anesthesia) >10mm/5min in the Eligible Eye at Week 4	19 Participants	4 Participants

PRIMARY outcome

Timeframe: At Week 12 (Visit 5 - Follow up)

Population: Full Analysis set (FAS): The FAS population consisted of all randomized patients who received at least 1 dose of the IMP. The FAS population was used for the primary analysis of the study and to present results on efficacy data. No units other than participants were assigned. While at baseline FAS patients were n=44 for IMP and 40 for Vehicle, at week 12 patients analyzed were n=40 in the IMP group and n=39 in the Vehicle arm. Please note that mean is an adjusted mean.

SANDE was a short questionnaire to evaluate both dry eye intensity and frequency. It uses a 100 mm horizontal line (Visual Analogue Scale - VAS), for each of the 2 questions, to assess ocular discomfort and/or dryness. Frequency of symptoms ranged from "rarely" (best outcome) to "all of the time" (worst outcome), while the severity of symptoms ranged from "very mild" (best outcome) to "very severe" (worst outcome). Patients had to place a mark on the two given lines based on the extent of their symptoms. The locations of the marks was measured in mm from left to right and recorded as frequency and severity scores, respectively. The SANDE lines for intensity and for severity ranged from 0, being the minimal amount of dry eye symptoms (best outcome) to 100, being the maximal amount of dry eye symptoms (worst outcome). The total SANDE score was calculated by multiplying the frequency score by the severity score and obtaining the square root (0-100; the lower, the better).

Outcome measures

Outcome measures
Measure	Cenegermin - FAS n=40 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. Cenegermin: 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=39 Participants In this arm one drop of vehicle was instilled in both eyes TID for 28 consecutive days. Vehicle: Vehicle was instilled with the same scheme of the test product
Change From Baseline in Symptom Questionnaire (SANDE) Global Score at Week 12	-12.452 score on a scale Interval -19.962 to -4.942	-13.042 score on a scale Interval -20.65 to -5.433

SECONDARY outcome

Timeframe: At Week 8 (Visit 4)

Population: Full Analysis set (FAS): The FAS population consisted of all randomized patients who received at least one dose of the investigational product. The FAS population was used for the primary analysis of the study and to present results on efficacy data. While at baseline FAS patients were n=44 for IMP and 40 for Vehicle, at week 8 patients analyzed were n=40 in the IMP group and n=38 in the Vehicle arm.

The Schirmer test was used in ophthalmic examination to measure tear production for the diagnosis of conditions such as keratoconjunctivitis sicca and dry eye. Without previously instilling anesthetic drops, the Schirmer strip was inserted into the lower conjunctival sac at the junction of the lateral and middle thirds, avoiding touching the cornea, and the length of wetting strips in millimeters was recorded after 5 minutes. After 5 minutes had elapsed, the Schirmer test strip was removed and the length of the tear absorption on the strip was measured (millimeters/5 minutes). Cutoff values: \<5 mm - pathologic dry eye 5-10 mm - marginal dry eye \>10 and \<30 mm - normal secretion The longer, the wetted length, the healthier the status of the eye. No units other than participants were assigned.

Outcome measures

Outcome measures
Measure	Cenegermin - FAS n=40 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. Cenegermin: 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=38 Participants In this arm one drop of vehicle was instilled in both eyes TID for 28 consecutive days. Vehicle: Vehicle was instilled with the same scheme of the test product
Key Secondary Outcome: Number of Patients With Schirmer I Test (Without Anesthesia) >10mm/5min at Week 8	11 Participants	2 Participants

SECONDARY outcome

Timeframe: At Week 12 (Visit 5 - Follow-up)

Population: Full Analysis set (FAS): The FAS population consisted of all randomized patients who received at least one dose of the investigational product. The FAS population was used for the primary analysis of the study and to present results on efficacy data. While at baseline FAS patients were n=44 for IMP and 40 for Vehicle, at week 4 patients analyzed were n=40 in the IMP group and n=39 in the Vehicle arm. Please note that mean is an adjusted mean.

The Symptom Assessment in Dry Eye (SANDE) questionnaire was a short questionnaire to evaluate both dry eye intensity/severity and frequency. This questionnaire used a 100 mm horizontal line (Visual Analogue Scale - VAS) for each of the 2 questions to assess ocular discomfort and/or dryness experienced by the patients. In the SANDE questionnaire, frequency of symptoms ranges from "rarely" to "all of the time" and the severity of symptoms ranged from "very mild" to "very severe". Patients were asked to place a mark on the two given lines based on the extent of their symptoms. The locations of the marks was measured in mm from left to right and recorded as frequency and severity scores, respectively. The SANDE scale ranged from 0, being the minimal amount of dry eye symptoms (best outcome) to 100, being the maximal amount of dry eye symptoms (worst outcome). In this outcome severity score at week 12 was assessed.

Outcome measures

Outcome measures
Measure	Cenegermin - FAS n=40 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. Cenegermin: 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=39 Participants In this arm one drop of vehicle was instilled in both eyes TID for 28 consecutive days. Vehicle: Vehicle was instilled with the same scheme of the test product
Key Secondary Outcome: Change From Baseline in Symptom Assessment in Dry Eye Questionnaire (SANDE) Score for Severity at Week 12	-11.851 score on a scale Interval -19.824 to -3.878	-12.072 score on a scale Interval -20.188 to -3.957

SECONDARY outcome

Timeframe: At Week 12 (Visit 5 - Follow-up)

Population: Full Analysis set (FAS): The FAS population consisted of all randomized patients who received at least one dose of the investigational product. The FAS population was used for the primary analysis of the study and to present results on efficacy data. While at baseline FAS patients were n=44 for IMP and 40 for Vehicle, at week 4 patients analyzed were n=40 in the IMP group and n=39 in the Vehicle arm. Please note that mean is an adjusted mean.

SANDE was a short questionnaire to evaluate both dry eye intensity and frequency. It uses a 100 mm horizontal line (Visual Analogue Scale, VAS), for each of the 2 questions, to assess ocular discomfort and/or dryness. Frequency of symptoms ranged from "rarely" (best outcome) to "all of the time" (worst outcome), while the severity of symptoms ranged from "very mild" (best outcome) to "very severe" (worst outcome). Patients had to place a mark on the two given lines based on the extent of their symptoms. The locations of the marks was measured in mm from left to right and recorded as frequency and severity scores, respectively. The SANDE lines for intensity and for severity ranged from 0, being the minimal amount of dry eye symptoms (best outcome) to 100, being the maximal amount of dry eye symptoms (worst outcome). The total SANDE score was calculated by multiplying the frequency score by the severity score and obtaining the square root (0-100; the lower, the better).

Outcome measures

Outcome measures
Measure	Cenegermin - FAS n=40 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. Cenegermin: 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=39 Participants In this arm one drop of vehicle was instilled in both eyes TID for 28 consecutive days. Vehicle: Vehicle was instilled with the same scheme of the test product
Key Secondary Outcome: Change From Baseline in Symptoms Assessment in Dry Eye Questionnaire (SANDE) Score for Frequency at Week 12	-14.606 score on a scale Interval -23.007 to -6.204	-14.770 score on a scale Interval -23.258 to -6.281

SECONDARY outcome

Timeframe: At Week 12 (Visit 5 - Follow-up) and Week 4 (Visit 3)

Population: Full Analysis set (FAS): it consisted of all randomized patients who received at least one dose of the IMP. The FAS population was used for the primary analysis and to present results on efficacy data. Patients at baseline were n=44 in the cenegermin arm and n=40 in the vehicle arm. At the other timepoints after baseline, a maximum of 43 cenegermin patients and 39 vehicle patients contributed data for this outcome within the FAS population.

IDEEL was a 57-item questionnaire that assessed the impact of dry eye symptoms on everyday life. It consisted of 3 modules: * Dry eye Quality of Life (27 items) composed by 3 dimensions: 1. Impact on Daily Activities 2. Emotional Impact 3. Impact on Work Scores for each dimension of this module ranged from 0 to 100, where higher scores indicated less impact on daily activities, on work and emotions. * Treatment Satisfaction \& Bother (8 items) composed by 2 dimensions: 1. Satisfaction with Treatment Effectiveness 2. Treatment-Related Bother / Inconvenience Scores for each dimension of this module range from 0 to 100, where higher scores indicate greater satisfaction with treatment effectiveness and less treatment-related bother. * Symptom Bother (20 items) composed by 1 dimension: 1. Dry Eye Symptom-Bother Scores for the dimension of this module ranged from 0 to 100, where higher scores indicated a greater symptom bother. No combination of dimensions scores was done.

Outcome measures

Outcome measures
Measure	Cenegermin - FAS n=43 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. Cenegermin: 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=39 Participants In this arm one drop of vehicle was instilled in both eyes TID for 28 consecutive days. Vehicle: Vehicle was instilled with the same scheme of the test product
Key Secondary Outcome: Change From Baseline in "Quality of Life, Dry Eye Treatment Satisfaction & Bother and Dry Eye Symptom-Bother" Modules Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 12 and at Week 4. QoL (Daily activities) - Week 4	13.690 score on a scale Interval 8.034 to 19.346	11.312 score on a scale Interval 5.393 to 17.231
Key Secondary Outcome: Change From Baseline in "Quality of Life, Dry Eye Treatment Satisfaction & Bother and Dry Eye Symptom-Bother" Modules Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 12 and at Week 4. QoL (Daily activities) - Week 12	13.769 score on a scale Interval 7.711 to 19.827	6.659 score on a scale Interval 0.549 to 12.769
Key Secondary Outcome: Change From Baseline in "Quality of Life, Dry Eye Treatment Satisfaction & Bother and Dry Eye Symptom-Bother" Modules Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 12 and at Week 4. QoL (Feelings) - Week 4	8.811 score on a scale Interval 2.356 to 15.266	12.977 score on a scale Interval 6.263 to 19.692
Key Secondary Outcome: Change From Baseline in "Quality of Life, Dry Eye Treatment Satisfaction & Bother and Dry Eye Symptom-Bother" Modules Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 12 and at Week 4. QoL (Feelings) - Week 12	11.413 score on a scale Interval 5.058 to 17.767	10.355 score on a scale Interval 3.923 to 16.787
Key Secondary Outcome: Change From Baseline in "Quality of Life, Dry Eye Treatment Satisfaction & Bother and Dry Eye Symptom-Bother" Modules Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 12 and at Week 4. QoL (Work) - Week 4	10.689 score on a scale Interval 2.183 to 19.195	14.596 score on a scale Interval 5.224 to 23.967
Key Secondary Outcome: Change From Baseline in "Quality of Life, Dry Eye Treatment Satisfaction & Bother and Dry Eye Symptom-Bother" Modules Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 12 and at Week 4. QoL (Work) - Week 12	13.225 score on a scale Interval 5.547 to 20.903	13.509 score on a scale Interval 5.084 to 21.934
Key Secondary Outcome: Change From Baseline in "Quality of Life, Dry Eye Treatment Satisfaction & Bother and Dry Eye Symptom-Bother" Modules Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 12 and at Week 4. Treatment Satisfaction (TS) (Treatment - in general) - Week 4	8.708 score on a scale Interval 2.786 to 14.63	8.757 score on a scale Interval 2.493 to 15.022
Key Secondary Outcome: Change From Baseline in "Quality of Life, Dry Eye Treatment Satisfaction & Bother and Dry Eye Symptom-Bother" Modules Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 12 and at Week 4. TS (Treatment - in general) - Week 12	7.281 score on a scale Interval 1.57 to 12.992	5.305 score on a scale Interval -0.513 to 11.124
Key Secondary Outcome: Change From Baseline in "Quality of Life, Dry Eye Treatment Satisfaction & Bother and Dry Eye Symptom-Bother" Modules Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 12 and at Week 4. Symptom-Bother - Week 4	-8.030 score on a scale Interval -13.302 to -2.758	-13.262 score on a scale Interval -18.758 to -7.766
Key Secondary Outcome: Change From Baseline in "Quality of Life, Dry Eye Treatment Satisfaction & Bother and Dry Eye Symptom-Bother" Modules Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 12 and at Week 4. Symptom-Bother - Week 12	-10.814 score on a scale Interval -16.22 to -5.407	-10.657 score on a scale Interval -16.102 to -5.212

SECONDARY outcome

Timeframe: At week 4 (Visit 3) , Week 8 (Visit 4), and Week 12 (Visit 5 - Follow-up)

Tear film break-up time (TFBUT) was the time taken to appear first dry spot on cornea after a complete blinking. TFBUT measurement was an easy and fast method used to assess the stability of tear film. It was a standard diagnostic procedure in the dry eye clinics. TFBUT was measured by determining the time to tear break-up. The TFBUT was performed after instillation of 5 μL of 2% preservative-free sodium fluorescein solution into the inferior conjunctival sac of each eye. The patient was instructed to blink several times to thoroughly mix the fluorescein with the tear film. A TFBUT greater than 15 seconds was considered normal, while a break time of less than 10 seconds was to be considered pathological. Hence, the shorter the time, the worse the outcome.

Outcome measures

Outcome measures
Measure	Cenegermin - FAS n=43 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. Cenegermin: 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=39 Participants In this arm one drop of vehicle was instilled in both eyes TID for 28 consecutive days. Vehicle: Vehicle was 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 and Week 12 Week 12	0.917 seconds Interval 0.123 to 1.711	0.782 seconds Interval -0.04 to 1.603
Key Secondary Outcome: Change From Baseline in Tear Film Break-Up Time (TFBUT) at Week 4, Week 8 and Week 12 Week 4	1.020 seconds Interval 0.253 to 1.787	0.225 seconds Interval -0.586 to 1.036
Key Secondary Outcome: Change From Baseline in Tear Film Break-Up Time (TFBUT) at Week 4, Week 8 and Week 12 Week 8	0.899 seconds Interval 0.074 to 1.725	0.951 seconds Interval 0.088 to 1.813

SECONDARY outcome

Timeframe: At Week 4 (Visit 3), Week 8 (Visit 4), Week 12 (Visit 5), and Week 16 (Visit 6)

Population: Full Analysis set (FAS): it consisted of all randomized patients who received at least one dose of the investigational product. The FAS population was used for the primary analysis of the study and to present results on efficacy data. While at baseline FAS patients were n=44 for IMP and 40 for Vehicle, patients analyzed were: n=43 at week 4; n=40 at weeks 8 and 12; n=41 at week 16 in the IMP arm and n=39 at weeks 4 and 12; n=40 at weeks 8 and 16 in the vehicle arm.

The Schirmer test was used in ophthalmic examination to measure tear production for the diagnosis of conditions such as keratoconjunctivitis sicca and dry eye. Without previously instilling anesthetic drops, the Schirmer strip was inserted into the lower conjunctival sac at the junction of the lateral and middle thirds, avoiding touching the cornea, and the length of wetting strips in millimeters was recorded after 5 minutes. After 5 minutes had elapsed, the Schirmer test strip was removed and the length of the tear absorption on the strip was measured (millimeters/5 minutes). Cutoff values: \<5 mm - pathologic dry eye 5-10 mm - marginal dry eye \>10 and \<30 mm - normal secretion The longer, the wetted length, the healthier the status of the eye.

Outcome measures

Outcome measures
Measure	Cenegermin - FAS n=43 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. Cenegermin: 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=39 Participants In this arm one drop of vehicle was instilled in both eyes TID for 28 consecutive days. Vehicle: Vehicle was instilled with the same scheme of the test product
Change From Baseline in Schirmer I Test (Without Anaesthesia) at Week 4, Week 8, Week 12, and Week 16 Week 4	5.4 millimeters Standard Deviation 5.2	1.7 millimeters Standard Deviation 3.2
Change From Baseline in Schirmer I Test (Without Anaesthesia) at Week 4, Week 8, Week 12, and Week 16 Week 8	4.9 millimeters Standard Deviation 4.5	1.5 millimeters Standard Deviation 3.0
Change From Baseline in Schirmer I Test (Without Anaesthesia) at Week 4, Week 8, Week 12, and Week 16 Week 12	4.1 millimeters Standard Deviation 4.7	3.1 millimeters Standard Deviation 6.3
Change From Baseline in Schirmer I Test (Without Anaesthesia) at Week 4, Week 8, Week 12, and Week 16 Week 16	3.4 millimeters Standard Deviation 4.0	2.4 millimeters Standard Deviation 4.9

SECONDARY outcome

Timeframe: At Week 4 (Visit 3), Week 8 (Visit 4) , Week 12 (Visit 5) and Week 16 (Visit 6)

Population: Full Analysis set (FAS): it consisted of all randomized patients who received at least one dose of the IMP. The FAS population was used for the primary analysis and to present results on efficacy data. Patients at baseline were n=44 in the cenegermin arm and n=40 in the vehicle arm. At the other timepoints after baseline, a maximum of 42 cenegermin patients and 37 vehicle patients contributed data for this outcome within the FAS population.

The NEI/Industry Workshop guidelines were used for grading the scale of corneal and conjunctival damage. The cornea was divided into five sectors (central, superior, inferior, nasal and temporal), each of which was scored on a scale of 0-3, with a maximal total corneal staining score of 15. Both nasally and temporally, the conjunctiva was divided into a superior paralimbal area, an inferior paralimbal area, and a peripheral area with a grading scale of 0-3 and with a maximal total score of 9 for the nasal and temporal conjunctiva (overall the total score ranged from 0-18). Briefly, grade 0 reflected normal/healthy situation, whereas grade 3 reflected a severe damage in the considered sector.

Outcome measures

Outcome measures
Measure	Cenegermin - FAS n=42 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. Cenegermin: 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=37 Participants In this arm one drop of vehicle was instilled in both eyes TID for 28 consecutive days. Vehicle: Vehicle was 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 4, Week 8, Week 12 and Week 16 corneal and conjunctival damage - Week 4	-3.6 score on a scale Standard Deviation 4.6	-2.4 score on a scale Standard Deviation 4.7
Change From Baseline in Cornea and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) at Week 4, Week 8, Week 12 and Week 16 corneal and conjunctival damage - Week 8	-3.1 score on a scale Standard Deviation 3.8	-2.9 score on a scale Standard Deviation 3.9
Change From Baseline in Cornea and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) at Week 4, Week 8, Week 12 and Week 16 corneal and conjunctival damage - Week 12	-3.4 score on a scale Standard Deviation 4.6	-3.0 score on a scale Standard Deviation 3.8
Change From Baseline in Cornea and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) at Week 4, Week 8, Week 12 and Week 16 corneal and conjunctival damage - Week 16	-2.0 score on a scale Standard Deviation 6.9	-2.3 score on a scale Standard Deviation 4.2

SECONDARY outcome

Timeframe: At Week 4 (Visit 3), Week 8 (Visit 4), Week 12 (Visit 5), and Week 16 (Visit 6)

Outcome measures

Outcome measures
Measure	Cenegermin - FAS n=43 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. Cenegermin: 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=39 Participants In this arm one drop of vehicle was instilled in both eyes TID for 28 consecutive days. Vehicle: Vehicle was instilled with the same scheme of the test product
Change From Baseline in Tear Film Break-Up Time (TFBUT) at Week 4, Week 8, Week 12 and Week 16 Week 4	1.1 seconds Standard Deviation 2.4	0.2 seconds Standard Deviation 2.2
Change From Baseline in Tear Film Break-Up Time (TFBUT) at Week 4, Week 8, Week 12 and Week 16 Week 8	0.9 seconds Standard Deviation 2.5	0.9 seconds Standard Deviation 2.3
Change From Baseline in Tear Film Break-Up Time (TFBUT) at Week 4, Week 8, Week 12 and Week 16 Week 12	1.0 seconds Standard Deviation 2.6	0.7 seconds Standard Deviation 1.8
Change From Baseline in Tear Film Break-Up Time (TFBUT) at Week 4, Week 8, Week 12 and Week 16 Week 16	1.3 seconds Standard Deviation 2.8	1.1 seconds Standard Deviation 2.5

SECONDARY outcome

Timeframe: At Week 8 (Visit 4), Week 12 (Visit 5), and Week 16 (Visit 6)

Population: Full Analysis set (FAS): it consisted of all randomized patients who received at least one dose of the IMP. The FAS population was used for the primary analysis and to present results on efficacy data. Patients at baseline were n=44 in the cenegermin arm and n=40 in the vehicle arm. At the other timepoints after baseline, a maximum of 41 cenegermin patients and 39 vehicle patients contributed data for this outcome within the FAS population. Please note that mean is an adjusted mean.

Outcome measures

Outcome measures
Measure	Cenegermin - FAS n=41 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. Cenegermin: 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=39 Participants In this arm one drop of vehicle was instilled in both eyes TID for 28 consecutive days. Vehicle: Vehicle was instilled with the same scheme of the test product
Change From Baseline in Symptoms Questionnaire (SANDE) Global Scores, and for Severity and Frequency at Week 8, Week 12, and Week 16 Global Score - Week 8	-12.9 score on a scale Standard Deviation 19.0	-10.3 score on a scale Standard Deviation 19.2
Change From Baseline in Symptoms Questionnaire (SANDE) Global Scores, and for Severity and Frequency at Week 8, Week 12, and Week 16 Global Score - Week 12	-9.5 score on a scale Standard Deviation 17.0	-11.3 score on a scale Standard Deviation 22.5
Change From Baseline in Symptoms Questionnaire (SANDE) Global Scores, and for Severity and Frequency at Week 8, Week 12, and Week 16 Global Score - Week 16	-9.0 score on a scale Standard Deviation 22.3	-11.1 score on a scale Standard Deviation 19.0
Change From Baseline in Symptoms Questionnaire (SANDE) Global Scores, and for Severity and Frequency at Week 8, Week 12, and Week 16 Severity - Week 8	-10.7 score on a scale Standard Deviation 19.6	-9.9 score on a scale Standard Deviation 20.9
Change From Baseline in Symptoms Questionnaire (SANDE) Global Scores, and for Severity and Frequency at Week 8, Week 12, and Week 16 Severity - Week 12	-8.6 score on a scale Standard Deviation 19.6	-10.2 score on a scale Standard Deviation 25.1
Change From Baseline in Symptoms Questionnaire (SANDE) Global Scores, and for Severity and Frequency at Week 8, Week 12, and Week 16 Severity - Week 16	-7.9 score on a scale Standard Deviation 22.9	-10.2 score on a scale Standard Deviation 20.2
Change From Baseline in Symptoms Questionnaire (SANDE) Global Scores, and for Severity and Frequency at Week 8, Week 12, and Week 16 Frequency - Week 8	-16.4 score on a scale Standard Deviation 23.2	-10.9 score on a scale Standard Deviation 21.2
Change From Baseline in Symptoms Questionnaire (SANDE) Global Scores, and for Severity and Frequency at Week 8, Week 12, and Week 16 Frequency - Week 12	-10.3 score on a scale Standard Deviation 23.6	-12.3 score on a scale Standard Deviation 23.5
Change From Baseline in Symptoms Questionnaire (SANDE) Global Scores, and for Severity and Frequency at Week 8, Week 12, and Week 16 Frequency - Week 16	-10.5 score on a scale Standard Deviation 24.2	-12.2 score on a scale Standard Deviation 18.6

SECONDARY outcome

Timeframe: At Week 4 (Visit 3)

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. Please note that mean is an adjusted mean.

Outcome measures

Outcome measures
Measure	Cenegermin - FAS n=43 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. Cenegermin: 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=39 Participants In this arm one drop of vehicle was instilled in both eyes TID for 28 consecutive days. Vehicle: Vehicle was instilled with the same scheme of the test product
Number of Patients Experienced a Worsening in Symptom Scores (SANDE Global Scores) and/or NEI Score ≥ 50% at Week 4 Worsening in symptom scores and/or NEI score >= 50	15 Participants	5 Participants
Number of Patients Experienced a Worsening in Symptom Scores (SANDE Global Scores) and/or NEI Score ≥ 50% at Week 4 Worsening in symptom scores (SANDE global score)	14 Participants	5 Participants
Number of Patients Experienced a Worsening in Symptom Scores (SANDE Global Scores) and/or NEI Score ≥ 50% at Week 4 NEI score >= 50%	1 Participants	1 Participants

SECONDARY outcome

Timeframe: At Week 4 (Visit 3), Week 8 (Visit 4), Week 12 (Visit 5), and Week 16 (Visit 6)

IDEEL was a 57-item questionnaire that assessed the impact of dry eye symptoms on everyday life. It consisted of 3 modules: * Dry eye Quality of Life (27 items) composed by 3 dimensions: 1. Impact on Daily Activities 2. Emotional Impact 3. Impact on Work Scores for each dimension of this module ranged from 0 to 100, where higher scores indicated less impact on daily activities, on work and emotions. * Treatment Satisfaction \& Bother (8 items) composed by 2 dimensions: 1. Satisfaction with Treatment Effectiveness 2. Treatment-Related Bother / Inconvenience Scores for each dimension of this module range from 0 to 100, where higher scores indicate greater satisfaction with treatment effectiveness and less treatment-related bother. * Symptom Bother (20 items) composed by 1 dimension: 1. Dry Eye Symptom-Bother. Scores for the dimension of this module ranged from 0 to 100, where higher scores indicated greater symptom bother. No combination of dimensions scores was done.

Outcome measures

Outcome measures
Measure	Cenegermin - FAS n=43 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. Cenegermin: 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=39 Participants In this arm one drop of vehicle was instilled in both eyes TID for 28 consecutive days. Vehicle: Vehicle was instilled with the same scheme of the test product
Change From Baseline in "Quality of Life, Dry Eye Treatment Satisfaction & Bother and Dry Eye Symptom-Bother" Modules Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 4, Week, 8, Week 12, and Week 16 QoL (Impact on Daily Activities) - Week 4	10.9 score on a scale Standard Deviation 20.7	10.3 score on a scale Standard Deviation 16.4
Change From Baseline in "Quality of Life, Dry Eye Treatment Satisfaction & Bother and Dry Eye Symptom-Bother" Modules Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 4, Week, 8, Week 12, and Week 16 QoL (Impact on Daily Activities) - Week 8	9.2 score on a scale Standard Deviation 20.6	7.2 score on a scale Standard Deviation 17.0
Change From Baseline in "Quality of Life, Dry Eye Treatment Satisfaction & Bother and Dry Eye Symptom-Bother" Modules Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 4, Week, 8, Week 12, and Week 16 QoL (Impact on Daily Activities) - Week 12	11.9 score on a scale Standard Deviation 20.8	5.6 score on a scale Standard Deviation 19.3
Change From Baseline in "Quality of Life, Dry Eye Treatment Satisfaction & Bother and Dry Eye Symptom-Bother" Modules Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 4, Week, 8, Week 12, and Week 16 QoL (Impact on Daily Activities) - Week 16	10.8 score on a scale Standard Deviation 19.6	8.1 score on a scale Standard Deviation 16.2
Change From Baseline in "Quality of Life, Dry Eye Treatment Satisfaction & Bother and Dry Eye Symptom-Bother" Modules Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 4, Week, 8, Week 12, and Week 16 QoL (Emotional Impact due to Dry Eye) - Week 4	4.3 score on a scale Standard Deviation 21.6	10.1 score on a scale Standard Deviation 17.5
Change From Baseline in "Quality of Life, Dry Eye Treatment Satisfaction & Bother and Dry Eye Symptom-Bother" Modules Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 4, Week, 8, Week 12, and Week 16 QoL (Emotional Impact due to Dry Eye) - Week 8	6.1 score on a scale Standard Deviation 20.0	8.5 score on a scale Standard Deviation 16.0
Change From Baseline in "Quality of Life, Dry Eye Treatment Satisfaction & Bother and Dry Eye Symptom-Bother" Modules Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 4, Week, 8, Week 12, and Week 16 QoL (Emotional Impact due to Dry Eye) - Week 12	7.4 score on a scale Standard Deviation 21.8	7.4 score on a scale Standard Deviation 16.6
Change From Baseline in "Quality of Life, Dry Eye Treatment Satisfaction & Bother and Dry Eye Symptom-Bother" Modules Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 4, Week, 8, Week 12, and Week 16 QoL (Emotional Impact due to Dry Eye) - Week 16	6.7 score on a scale Standard Deviation 25.0	7.6 score on a scale Standard Deviation 16.1
Change From Baseline in "Quality of Life, Dry Eye Treatment Satisfaction & Bother and Dry Eye Symptom-Bother" Modules Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 4, Week, 8, Week 12, and Week 16 QoL (Impact on Work due to Dry Eye) - Week 4	9.8 score on a scale Standard Deviation 24.7	13.4 score on a scale Standard Deviation 16.1
Change From Baseline in "Quality of Life, Dry Eye Treatment Satisfaction & Bother and Dry Eye Symptom-Bother" Modules Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 4, Week, 8, Week 12, and Week 16 QoL (Impact on Work due to Dry Eye) - Week 8	9.5 score on a scale Standard Deviation 21.7	8.1 score on a scale Standard Deviation 14.3
Change From Baseline in "Quality of Life, Dry Eye Treatment Satisfaction & Bother and Dry Eye Symptom-Bother" Modules Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 4, Week, 8, Week 12, and Week 16 QoL (Impact on Work due to Dry Eye) - Week 12	10.4 score on a scale Standard Deviation 19.9	11.8 score on a scale Standard Deviation 20.0
Change From Baseline in "Quality of Life, Dry Eye Treatment Satisfaction & Bother and Dry Eye Symptom-Bother" Modules Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 4, Week, 8, Week 12, and Week 16 QoL (Impact on Work due to Dry Eye) - Week 16	13.6 score on a scale Standard Deviation 21.3	8.9 score on a scale Standard Deviation 15.1
Change From Baseline in "Quality of Life, Dry Eye Treatment Satisfaction & Bother and Dry Eye Symptom-Bother" Modules Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 4, Week, 8, Week 12, and Week 16 TS (Satisfaction with Effectiveness) - Week 4	11.3 score on a scale Standard Deviation 30.4	10.1 score on a scale Standard Deviation 25.1
Change From Baseline in "Quality of Life, Dry Eye Treatment Satisfaction & Bother and Dry Eye Symptom-Bother" Modules Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 4, Week, 8, Week 12, and Week 16 TS (Satisfaction with Effectiveness) - Week 8	12.0 score on a scale Standard Deviation 25.5	5.2 score on a scale Standard Deviation 25.2
Change From Baseline in "Quality of Life, Dry Eye Treatment Satisfaction & Bother and Dry Eye Symptom-Bother" Modules Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 4, Week, 8, Week 12, and Week 16 TS (Satisfaction with Effectiveness) - Week 12	13.1 score on a scale Standard Deviation 26.8	7.4 score on a scale Standard Deviation 25.7
Change From Baseline in "Quality of Life, Dry Eye Treatment Satisfaction & Bother and Dry Eye Symptom-Bother" Modules Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 4, Week, 8, Week 12, and Week 16 TS (Satisfaction with Effectiveness) - Week 16	13.1 score on a scale Standard Deviation 29.0	7.9 score on a scale Standard Deviation 26.1
Change From Baseline in "Quality of Life, Dry Eye Treatment Satisfaction & Bother and Dry Eye Symptom-Bother" Modules Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 4, Week, 8, Week 12, and Week 16 TS (Treatment Bother/Inconvenience) - Week 4	5.5 score on a scale Standard Deviation 21.7	6.2 score on a scale Standard Deviation 12.7
Change From Baseline in "Quality of Life, Dry Eye Treatment Satisfaction & Bother and Dry Eye Symptom-Bother" Modules Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 4, Week, 8, Week 12, and Week 16 TS (Treatment Bother/Inconvenience) - Week 8	3.3 score on a scale Standard Deviation 18.9	5.0 score on a scale Standard Deviation 14.8
Change From Baseline in "Quality of Life, Dry Eye Treatment Satisfaction & Bother and Dry Eye Symptom-Bother" Modules Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 4, Week, 8, Week 12, and Week 16 TS (Treatment Bother/Inconvenience) - Week 12	4.5 score on a scale Standard Deviation 19.8	4.2 score on a scale Standard Deviation 12.4
Change From Baseline in "Quality of Life, Dry Eye Treatment Satisfaction & Bother and Dry Eye Symptom-Bother" Modules Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 4, Week, 8, Week 12, and Week 16 TS (Treatment Bother/Inconvenience) - Week 16	5.4 score on a scale Standard Deviation 18.5	3.3 score on a scale Standard Deviation 11.3
Change From Baseline in "Quality of Life, Dry Eye Treatment Satisfaction & Bother and Dry Eye Symptom-Bother" Modules Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 4, Week, 8, Week 12, and Week 16 Symptom-Bother - Week 4	-5.8 score on a scale Standard Deviation 18.7	-11.9 score on a scale Standard Deviation 12.5
Change From Baseline in "Quality of Life, Dry Eye Treatment Satisfaction & Bother and Dry Eye Symptom-Bother" Modules Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 4, Week, 8, Week 12, and Week 16 Symptom-Bother - Week 8	-7.2 score on a scale Standard Deviation 16.4	-7.9 score on a scale Standard Deviation 12.9
Change From Baseline in "Quality of Life, Dry Eye Treatment Satisfaction & Bother and Dry Eye Symptom-Bother" Modules Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 4, Week, 8, Week 12, and Week 16 Symptom-Bother - Week 12	-8.6 score on a scale Standard Deviation 15.5	-9.5 score on a scale Standard Deviation 17.7
Change From Baseline in "Quality of Life, Dry Eye Treatment Satisfaction & Bother and Dry Eye Symptom-Bother" Modules Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 4, Week, 8, Week 12, and Week 16 Symptom-Bother - Week 16	-8.0 score on a scale Standard Deviation 17.0	-9.2 score on a scale Standard Deviation 13.9

OTHER_PRE_SPECIFIED outcome

Timeframe: From Screening day (Day -8) up to Week 24 (Visit 7 - Follow-up)

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

Treatment emergent adverse events (TEAEs) were undesirable events not present prior to medical treatment, or an already present event that worsens either in intensity or frequency following the treatment.

Outcome measures

Outcome measures
Measure	Cenegermin - FAS n=44 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. Cenegermin: 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=40 Participants In this arm one drop of vehicle was instilled in both eyes TID for 28 consecutive days. Vehicle: Vehicle was instilled with the same scheme of the test product
Number of Patients With at Least One Treatment-emergent Adverse Event (TEAE) From Screening Day to Week 24 Any TEAE leading to death	0 Participants	0 Participants
Number of Patients With at Least One Treatment-emergent Adverse Event (TEAE) From Screening Day to Week 24 Any severe TEAE - Ophtalmic	0 Participants	1 Participants
Number of Patients With at Least One Treatment-emergent Adverse Event (TEAE) From Screening Day to Week 24 Any severe TEAE - Non-ophtalmic	0 Participants	0 Participants
Number of Patients With at Least One Treatment-emergent Adverse Event (TEAE) From Screening Day to Week 24 Any serious TEAE	0 Participants	0 Participants
Number of Patients With at Least One Treatment-emergent Adverse Event (TEAE) From Screening Day to Week 24 Any serious TEAE - Ophtalmic	0 Participants	0 Participants
Number of Patients With at Least One Treatment-emergent Adverse Event (TEAE) From Screening Day to Week 24 Any serious TEAE - Non-ophtalmic	0 Participants	0 Participants
Number of Patients With at Least One Treatment-emergent Adverse Event (TEAE) From Screening Day to Week 24 Any non-serious TEAE	27 Participants	18 Participants
Number of Patients With at Least One Treatment-emergent Adverse Event (TEAE) From Screening Day to Week 24 Any ADR	26 Participants	12 Participants
Number of Patients With at Least One Treatment-emergent Adverse Event (TEAE) From Screening Day to Week 24 Any ADR - Ophtalmic	26 Participants	10 Participants
Number of Patients With at Least One Treatment-emergent Adverse Event (TEAE) From Screening Day to Week 24 Any ADR - Non-ophtalmic	3 Participants	4 Participants
Number of Patients With at Least One Treatment-emergent Adverse Event (TEAE) From Screening Day to Week 24 Any Serious ADR	0 Participants	0 Participants
Number of Patients With at Least One Treatment-emergent Adverse Event (TEAE) From Screening Day to Week 24 Any Serious ADR leading to IMP discontinuation	0 Participants	1 Participants
Number of Patients With at Least One Treatment-emergent Adverse Event (TEAE) From Screening Day to Week 24 Any TEAE leading to study discontinuation	0 Participants	1 Participants
Number of Patients With at Least One Treatment-emergent Adverse Event (TEAE) From Screening Day to Week 24 Any TEAE	27 Participants	18 Participants
Number of Patients With at Least One Treatment-emergent Adverse Event (TEAE) From Screening Day to Week 24 Any TEAE - Ophtalmic	26 Participants	12 Participants
Number of Patients With at Least One Treatment-emergent Adverse Event (TEAE) From Screening Day to Week 24 Any TEAE . Non-ophtalmic	9 Participants	9 Participants
Number of Patients With at Least One Treatment-emergent Adverse Event (TEAE) From Screening Day to Week 24 Any severe TEAE	0 Participants	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Treatment period (Day 1 to Week 4), Follow-up period (Week 4 to Week 24), Overall period (Day 1 to Week 24)

Population: Full Analysis set (FAS): it consisted of all randomized patients who received at least one dose of the IMP. The FAS population was used for the primary analysis and to present results on efficacy data. Patients at baseline were n=44 in the cenegermin arm and n=40 in the vehicle arm. At the other timepoints after baseline, a maximum of 41 cenegermin patients and 38 vehicle patients contributed data for this outcome within the FAS population.

Use of Preservative Free Artificial Tears by Study Period is calculated as: total number of drops of the preservative free artificial tears during the X period/ total number of days of the X period \* 100.

Outcome measures

Outcome measures
Measure	Cenegermin - FAS n=41 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. Cenegermin: 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=38 Participants In this arm one drop of vehicle was instilled in both eyes TID for 28 consecutive days. Vehicle: Vehicle was instilled with the same scheme of the test product
Use of Preservative Free Artificial Tears Use (Number of Drops/Day). Treatment period	261.2 number of drops Standard Deviation 220.2	215.7 number of drops Standard Deviation 184.7
Use of Preservative Free Artificial Tears Use (Number of Drops/Day). Follow-up period	330.0 number of drops Standard Deviation 178.1	317.6 number of drops Standard Deviation 168.3
Use of Preservative Free Artificial Tears Use (Number of Drops/Day). Overall period	294.7 number of drops Standard Deviation 202.5	268.1 number of drops Standard Deviation 182.6

OTHER_PRE_SPECIFIED outcome

Timeframe: At week 2 (Visit 2)

Population: Full Analysis set (FAS): The FAS population consisted of all randomized patients who received at least one dose of the investigational product. While at baseline FAS patients were n=44 for IMP and 40 for Vehicle, at week 2 patients analyzed were n=43 in the IMP group and n=39 in the Vehicle arm.

The Schirmer test was used in ophthalmic examination to measure tear production for the diagnosis of conditions such as keratoconjunctivitis sicca and dry eye. Without previously instilling anesthetic drops, the Schirmer strip was inserted into the lower conjunctival sac at the junction of the lateral and middle thirds, avoiding touching the cornea, and the length of wetting strips in millimeters was recorded after 5 minutes. After 5 minutes had elapsed, the Schirmer test strip was removed and the length of the tear absorption on the strip was measured (millimeters/5 minutes). Cutoff values: \<5 mm - pathologic dry eye 5-10 mm - marginal dry eye \>10 and \<30 mm - normal secretion The longer, the wetted length, the healthier the status of the eye.

Outcome measures

Outcome measures
Measure	Cenegermin - FAS n=43 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. Cenegermin: 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=39 Participants In this arm one drop of vehicle was instilled in both eyes TID for 28 consecutive days. Vehicle: Vehicle was instilled with the same scheme of the test product
Change From Baseline in Schirmer I Test (Without Anaesthesia) at Week 2	4.4 millimeters Standard Deviation 5.0	1.0 millimeters Standard Deviation 2.4

OTHER_PRE_SPECIFIED outcome

Timeframe: At Week 2 (Visit 2)

Population: Full Analysis set (FAS): The FAS population consisted of all randomized patients who received at least one dose of the investigational product. FAS population was analysed according to intention-to-treat (ITT) principle, i.e., by treatment allocation regardless happening of intercurrent events (treatment policy strategy). Herein the Number Participants Analyzed in Cenergermin group was 42, in the Vehicle group was 37.

Outcome measures

Outcome measures
Measure	Cenegermin - FAS n=42 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. Cenegermin: 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=37 Participants In this arm one drop of vehicle was instilled in both eyes TID for 28 consecutive days. Vehicle: Vehicle was 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 2	-2.6 score on a scale Standard Deviation 4.8	-2.0 score on a scale Standard Deviation 5.2

OTHER_PRE_SPECIFIED outcome

Timeframe: At Week 2 (Visit 2)

Outcome measures

Outcome measures
Measure	Cenegermin - FAS n=43 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. Cenegermin: 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=39 Participants In this arm one drop of vehicle was instilled in both eyes TID for 28 consecutive days. Vehicle: Vehicle was instilled with the same scheme of the test product
Change From Baseline in Tear Film Break-Up Time (TFBUT) at Week 2	0.7 seconds Standard Deviation 2.1	0.2 seconds Standard Deviation 2.0

OTHER_PRE_SPECIFIED outcome

Timeframe: At Week 2 (Visit 2) and Week 4 (Visit 3)

Population: Full Analysis set (FAS): it consisted of all randomized patients who received at least one dose of the IMP. The FAS population was used for the primary analysis and to present results on efficacy data. Patients at baseline were n=44 in the cenegermin arm and n=40 in the vehicle arm. At the other timepoints after baseline, only 43 cenegermin patients and 39 vehicle patients contributed data for this outcome within the FAS population. Please note that mean is an adjusted mean.

Outcome measures

Outcome measures
Measure	Cenegermin - FAS n=43 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. Cenegermin: 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=39 Participants In this arm one drop of vehicle was instilled in both eyes TID for 28 consecutive days. Vehicle: Vehicle was instilled with the same scheme of the test product
Change From Baseline in Symptoms Questionnaire (SANDE) Global Scores, and for Severity and Frequency at Week 2, and Week 4 Global Score - Change from baseline to Week 2	-2.1 score on a scale Standard Deviation 18.0	-12.3 score on a scale Standard Deviation 13.7
Change From Baseline in Symptoms Questionnaire (SANDE) Global Scores, and for Severity and Frequency at Week 2, and Week 4 Global Score - Change from baseline to Week 4	-11.5 score on a scale Standard Deviation 17.4	-15.0 score on a scale Standard Deviation 18.0
Change From Baseline in Symptoms Questionnaire (SANDE) Global Scores, and for Severity and Frequency at Week 2, and Week 4 Severity - Change from baseline to Week 2	-0.5 score on a scale Standard Deviation 20.1	-12.3 score on a scale Standard Deviation 14.9
Change From Baseline in Symptoms Questionnaire (SANDE) Global Scores, and for Severity and Frequency at Week 2, and Week 4 Severity - Change from baseline to Week 4	-9.2 score on a scale Standard Deviation 19.7	-13.6 score on a scale Standard Deviation 17.2
Change From Baseline in Symptoms Questionnaire (SANDE) Global Scores, and for Severity and Frequency at Week 2, and Week 4 Frequency - Change from baseline to Week 2	-3.8 score on a scale Standard Deviation 18.9	-12.0 score on a scale Standard Deviation 14.7
Change From Baseline in Symptoms Questionnaire (SANDE) Global Scores, and for Severity and Frequency at Week 2, and Week 4 Frequency - Change from baseline to Week 4	-14.5 score on a scale Standard Deviation 18.8	-16.9 score on a scale Standard Deviation 22.2

OTHER_PRE_SPECIFIED outcome

Timeframe: At Week 2 (Visit 2)

Outcome measures

Outcome measures
Measure	Cenegermin - FAS n=43 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. Cenegermin: 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=39 Participants In this arm one drop of vehicle was instilled in both eyes TID for 28 consecutive days. Vehicle: Vehicle was instilled with the same scheme of the test product
Number of Patients Experienced a Worsening in Symptom Scores (SANDE Global Score) and/or NEI Score ≥ 50% Assessed at Week 2 NEI score >= 50%	1 Participants	0 Participants
Number of Patients Experienced a Worsening in Symptom Scores (SANDE Global Score) and/or NEI Score ≥ 50% Assessed at Week 2 Worsening in symptom scores (SANDE global score)	17 Participants	5 Participants
Number of Patients Experienced a Worsening in Symptom Scores (SANDE Global Score) and/or NEI Score ≥ 50% Assessed at Week 2 Worsening in symptom scores and/or NEI score >= 50	18 Participants	5 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: At Week 4 (Visit 3)

Population: Full Analysis set (FAS): The FAS population consisted of all randomized patients who received at least one dose of the investigational product. While at baseline FAS patients were n=44 for IMP and 40 for Vehicle, at week 4 patients analyzed were n=42 in the IMP group and n=38 in the Vehicle arm.

Schirmer Test II (with anaesthetic) measured baseline plus reflex secretion. The Schirmer strip was inserted into the lower conjunctival sac at the junction of the lateral and middle thirds, avoiding touching the cornea, and the length of wetting strips in millimeters was recorded after 5 minutes. After 5 minutes had elapsed, the Schirmer test strip was removed and the length of the tear absorption on the strip was measured (millimeters/5 minutes). Cutoff values: \<5 mm - pathologic dry eye 5-10 mm - marginal dry eye \>10 and \<30 mm - normal secretion The longer, the wetted length, the healthier the status of the eye.

Outcome measures

Outcome measures
Measure	Cenegermin - FAS n=42 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. Cenegermin: 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=38 Participants In this arm one drop of vehicle was instilled in both eyes TID for 28 consecutive days. Vehicle: Vehicle was instilled with the same scheme of the test product
Change From Baseline in Schirmer Test II (With Topical Anaesthesia) at Week 4	4.3 millimeters Standard Deviation 4.2	1.4 millimeters Standard Deviation 3.7

OTHER_PRE_SPECIFIED outcome

Timeframe: At Week 2 (Visit 2), Week 4 (Visit 3), Week 8 (Visit 4), Week 12 (Visit 5), and Week 16 (Visit 6)

Best corrected visual acuity (BCDVA) was determined by careful refraction according to the standard protocol for refraction. Chart 1 was used for testing the VA of the right eye; Chart 2 for the left eye; and Chart R for refraction only. Retroilluminated standard Early Treatment of Diabetic Retinopathy Study (ETDRS) charts were used. They had 5 Sloan letters on each line of equal difficulty, and there was a geometric progression in letter size from line to line. VAS awarded one point for every letter correctly guessed. A distance of 4 meters was required between the subject's eyes and the VA chart. When a subject cannot read at least 20 letters on the chart at 4 meters, the subject was tested at 1 meter. If 20 or more letters were read at 4 meters, the VAS for that eye was recorded as the number of letters correct at 4 meters plus 30. Otherwise, the VAS was the number of letters read correctly at 1 meter plus the number read at 4 meters. The higher the score the better the outcome.

Outcome measures

Outcome measures
Measure	Cenegermin - FAS n=43 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. Cenegermin: 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=39 Participants In this arm one drop of vehicle was instilled in both eyes TID for 28 consecutive days. Vehicle: Vehicle was instilled with the same scheme of the test product
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 2 - No change	32 Participants	29 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 2 - 20/63 to 20/40	0 Participants	1 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 2 - 20/50 to 20/40	0 Participants	1 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 2 - 20/40 to 20/25	1 Participants	1 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 2 - 20/32 to 20/20	1 Participants	0 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 2 - 20/32 to 20/25	1 Participants	1 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 2 - 20/25 to 20/20	3 Participants	2 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 2 - 20/20 to 20/16	2 Participants	0 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 2 - 20/20 to 20/25	1 Participants	2 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 2 - 20/16 to 20/12.5	0 Participants	1 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 2 - 20/16 to 20/20	1 Participants	0 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 2 - 20/16 to 20/25	1 Participants	0 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 2 - 20/16 to 20/32	0 Participants	1 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 4 - No change	31 Participants	33 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 4 - 20/63 to 20/40	0 Participants	1 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 4 - 20/40 to 20/25	1 Participants	1 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 4 - 20/40 to 20/32	1 Participants	0 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 4 - 20/32 to 20/20	0 Participants	1 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 4 - 20/32 to 20/25	1 Participants	0 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 4 - 20/25 to 20/20	3 Participants	2 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 4 - 20/20 to 20/25	3 Participants	0 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 4 - 20/20 to 20/32	1 Participants	0 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 4 - 20/16 to 20/20	2 Participants	0 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 4 - 20/16 to 20/32	0 Participants	1 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 8 - No change	26 Participants	29 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 8 - 20/63 to 20/40	0 Participants	1 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 8 - 20/50 to 20/40	0 Participants	1 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 8 - 20/40 to 20/20	0 Participants	1 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 8 -20/40 to 20/25	1 Participants	0 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 8 -20/40 to 20/32	1 Participants	0 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 8 - 20/40 to 20/50	1 Participants	0 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 8 -20/32 to 20/20	1 Participants	0 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 8 -20/32 to 20/25	1 Participants	1 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 8 - 20/25 to 20/20	2 Participants	1 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 8 - 20/25 to 20/32	1 Participants	0 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 8 - 20/20 to 20/16	2 Participants	1 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 8 - 20/20 to 20/25	2 Participants	2 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 8 - 20/16 to 20/20	2 Participants	0 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 8 -20/16 to 20/32	0 Participants	1 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 12 - no change	29 Participants	30 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 12 - 20/63 to 20/80	0 Participants	1 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 12 -20/50 to 20/63	0 Participants	1 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 12 -20/40 to 20/20	0 Participants	1 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 12 - 20/40 to 20/32	1 Participants	0 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 12 - 20/32 to 20/20	1 Participants	0 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 12 - 20/32 to 20/25	1 Participants	1 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 12 - 20/25 to 20/20	3 Participants	1 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 12 - 20/25 to 20/32	1 Participants	0 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 12 - 20/20 to 20/16	0 Participants	1 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 12 -20/20 to 20/25	1 Participants	2 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 12 - 20/20 to 20/32	1 Participants	0 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 12 -20/16 to 20/20	1 Participants	0 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 12 -20/16 to 20/50	0 Participants	1 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 12 - 20/12.5 to 20/16	1 Participants	0 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 16 - no change	25 Participants	27 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 16 -20/63 to 20/50	0 Participants	1 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 16 -20/50 to 20/40	0 Participants	1 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 16 - 20/40 to 20/20	0 Participants	1 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 16 -20/40 to 20/25	1 Participants	0 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 16 -20/40 to 20/32	1 Participants	0 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 16 - 20/40 to 20/50	1 Participants	0 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 16 -20/32 to 20/25	2 Participants	2 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 16 -20/25 to 20/16	0 Participants	1 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 16 -20/25 to 20/20	4 Participants	0 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 16 -20/25 to 20/32	0 Participants	2 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 16 -20/20 to 20/16	3 Participants	0 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 16 -20/20 to 20/25	2 Participants	2 Participants
Change From Baseline in Best Corrected Distance Visual Acuity (BCDVA) CFB to Week 16 -20/16 to 20/20	2 Participants	1 Participants

Adverse Events

Cenegermin - SAF

Serious events: 0 serious events

Other events: 27 other events

Deaths: 0 deaths

Vehicle - SAF

Serious events: 0 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Cenegermin - SAF n=44 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. Cenegermin: 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=40 participants at risk In this arm one drop of vehicle was instilled in both eyes TID for 28 consecutive days. Vehicle: Vehicle was instilled with the same scheme of the test product
Eye disorders Conjunctival hyperaemia	4.5% 2/44 • Number of events 2 • AEs were collected from the screening visit (Day -8) until last Follow-Up visit (Week 24). An AE was defined as any untoward medical occurrence in a patient or clinical investigation patient administered a medicinal product and which did not necessarily have a causal relationship with this treatment. Please note that analyses in NGF0221 were done at the patient level, not by eye, so adverse events reported may refer to the study eye, the non-study eye, or both, indifferently.	2.5% 1/40 • Number of events 1 • AEs were collected from the screening visit (Day -8) until last Follow-Up visit (Week 24). An AE was defined as any untoward medical occurrence in a patient or clinical investigation patient administered a medicinal product and which did not necessarily have a causal relationship with this treatment. Please note that analyses in NGF0221 were done at the patient level, not by eye, so adverse events reported may refer to the study eye, the non-study eye, or both, indifferently.
Eye disorders Dry eye	0.00% 0/44 • AEs were collected from the screening visit (Day -8) until last Follow-Up visit (Week 24). An AE was defined as any untoward medical occurrence in a patient or clinical investigation patient administered a medicinal product and which did not necessarily have a causal relationship with this treatment. Please note that analyses in NGF0221 were done at the patient level, not by eye, so adverse events reported may refer to the study eye, the non-study eye, or both, indifferently.	7.5% 3/40 • Number of events 3 • AEs were collected from the screening visit (Day -8) until last Follow-Up visit (Week 24). An AE was defined as any untoward medical occurrence in a patient or clinical investigation patient administered a medicinal product and which did not necessarily have a causal relationship with this treatment. Please note that analyses in NGF0221 were done at the patient level, not by eye, so adverse events reported may refer to the study eye, the non-study eye, or both, indifferently.
Eye disorders Eye discharge	4.5% 2/44 • Number of events 2 • AEs were collected from the screening visit (Day -8) until last Follow-Up visit (Week 24). An AE was defined as any untoward medical occurrence in a patient or clinical investigation patient administered a medicinal product and which did not necessarily have a causal relationship with this treatment. Please note that analyses in NGF0221 were done at the patient level, not by eye, so adverse events reported may refer to the study eye, the non-study eye, or both, indifferently.	5.0% 2/40 • Number of events 3 • AEs were collected from the screening visit (Day -8) until last Follow-Up visit (Week 24). An AE was defined as any untoward medical occurrence in a patient or clinical investigation patient administered a medicinal product and which did not necessarily have a causal relationship with this treatment. Please note that analyses in NGF0221 were done at the patient level, not by eye, so adverse events reported may refer to the study eye, the non-study eye, or both, indifferently.
Eye disorders Eye irritation	4.5% 2/44 • Number of events 2 • AEs were collected from the screening visit (Day -8) until last Follow-Up visit (Week 24). An AE was defined as any untoward medical occurrence in a patient or clinical investigation patient administered a medicinal product and which did not necessarily have a causal relationship with this treatment. Please note that analyses in NGF0221 were done at the patient level, not by eye, so adverse events reported may refer to the study eye, the non-study eye, or both, indifferently.	2.5% 1/40 • Number of events 1 • AEs were collected from the screening visit (Day -8) until last Follow-Up visit (Week 24). An AE was defined as any untoward medical occurrence in a patient or clinical investigation patient administered a medicinal product and which did not necessarily have a causal relationship with this treatment. Please note that analyses in NGF0221 were done at the patient level, not by eye, so adverse events reported may refer to the study eye, the non-study eye, or both, indifferently.
Eye disorders Eye pain	47.7% 21/44 • Number of events 23 • AEs were collected from the screening visit (Day -8) until last Follow-Up visit (Week 24). An AE was defined as any untoward medical occurrence in a patient or clinical investigation patient administered a medicinal product and which did not necessarily have a causal relationship with this treatment. Please note that analyses in NGF0221 were done at the patient level, not by eye, so adverse events reported may refer to the study eye, the non-study eye, or both, indifferently.	10.0% 4/40 • Number of events 4 • AEs were collected from the screening visit (Day -8) until last Follow-Up visit (Week 24). An AE was defined as any untoward medical occurrence in a patient or clinical investigation patient administered a medicinal product and which did not necessarily have a causal relationship with this treatment. Please note that analyses in NGF0221 were done at the patient level, not by eye, so adverse events reported may refer to the study eye, the non-study eye, or both, indifferently.
Eye disorders Foreign body sensation in eyes	0.00% 0/44 • AEs were collected from the screening visit (Day -8) until last Follow-Up visit (Week 24). An AE was defined as any untoward medical occurrence in a patient or clinical investigation patient administered a medicinal product and which did not necessarily have a causal relationship with this treatment. Please note that analyses in NGF0221 were done at the patient level, not by eye, so adverse events reported may refer to the study eye, the non-study eye, or both, indifferently.	5.0% 2/40 • Number of events 2 • AEs were collected from the screening visit (Day -8) until last Follow-Up visit (Week 24). An AE was defined as any untoward medical occurrence in a patient or clinical investigation patient administered a medicinal product and which did not necessarily have a causal relationship with this treatment. Please note that analyses in NGF0221 were done at the patient level, not by eye, so adverse events reported may refer to the study eye, the non-study eye, or both, indifferently.
Eye disorders Photophobia	4.5% 2/44 • Number of events 2 • AEs were collected from the screening visit (Day -8) until last Follow-Up visit (Week 24). An AE was defined as any untoward medical occurrence in a patient or clinical investigation patient administered a medicinal product and which did not necessarily have a causal relationship with this treatment. Please note that analyses in NGF0221 were done at the patient level, not by eye, so adverse events reported may refer to the study eye, the non-study eye, or both, indifferently.	0.00% 0/40 • AEs were collected from the screening visit (Day -8) until last Follow-Up visit (Week 24). An AE was defined as any untoward medical occurrence in a patient or clinical investigation patient administered a medicinal product and which did not necessarily have a causal relationship with this treatment. Please note that analyses in NGF0221 were done at the patient level, not by eye, so adverse events reported may refer to the study eye, the non-study eye, or both, indifferently.
Eye disorders Swelling of eyelid	4.5% 2/44 • Number of events 2 • AEs were collected from the screening visit (Day -8) until last Follow-Up visit (Week 24). An AE was defined as any untoward medical occurrence in a patient or clinical investigation patient administered a medicinal product and which did not necessarily have a causal relationship with this treatment. Please note that analyses in NGF0221 were done at the patient level, not by eye, so adverse events reported may refer to the study eye, the non-study eye, or both, indifferently.	2.5% 1/40 • Number of events 1 • AEs were collected from the screening visit (Day -8) until last Follow-Up visit (Week 24). An AE was defined as any untoward medical occurrence in a patient or clinical investigation patient administered a medicinal product and which did not necessarily have a causal relationship with this treatment. Please note that analyses in NGF0221 were done at the patient level, not by eye, so adverse events reported may refer to the study eye, the non-study eye, or both, indifferently.
Eye disorders Vision blurred	2.3% 1/44 • Number of events 1 • AEs were collected from the screening visit (Day -8) until last Follow-Up visit (Week 24). An AE was defined as any untoward medical occurrence in a patient or clinical investigation patient administered a medicinal product and which did not necessarily have a causal relationship with this treatment. Please note that analyses in NGF0221 were done at the patient level, not by eye, so adverse events reported may refer to the study eye, the non-study eye, or both, indifferently.	5.0% 2/40 • Number of events 2 • AEs were collected from the screening visit (Day -8) until last Follow-Up visit (Week 24). An AE was defined as any untoward medical occurrence in a patient or clinical investigation patient administered a medicinal product and which did not necessarily have a causal relationship with this treatment. Please note that analyses in NGF0221 were done at the patient level, not by eye, so adverse events reported may refer to the study eye, the non-study eye, or both, indifferently.
Eye disorders Eyelid pain	15.9% 7/44 • Number of events 9 • AEs were collected from the screening visit (Day -8) until last Follow-Up visit (Week 24). An AE was defined as any untoward medical occurrence in a patient or clinical investigation patient administered a medicinal product and which did not necessarily have a causal relationship with this treatment. Please note that analyses in NGF0221 were done at the patient level, not by eye, so adverse events reported may refer to the study eye, the non-study eye, or both, indifferently.	0.00% 0/40 • AEs were collected from the screening visit (Day -8) until last Follow-Up visit (Week 24). An AE was defined as any untoward medical occurrence in a patient or clinical investigation patient administered a medicinal product and which did not necessarily have a causal relationship with this treatment. Please note that analyses in NGF0221 were done at the patient level, not by eye, so adverse events reported may refer to the study eye, the non-study eye, or both, indifferently.
Injury, poisoning and procedural complications Rib fracture	4.5% 2/44 • Number of events 2 • AEs were collected from the screening visit (Day -8) until last Follow-Up visit (Week 24). An AE was defined as any untoward medical occurrence in a patient or clinical investigation patient administered a medicinal product and which did not necessarily have a causal relationship with this treatment. Please note that analyses in NGF0221 were done at the patient level, not by eye, so adverse events reported may refer to the study eye, the non-study eye, or both, indifferently.	0.00% 0/40 • AEs were collected from the screening visit (Day -8) until last Follow-Up visit (Week 24). An AE was defined as any untoward medical occurrence in a patient or clinical investigation patient administered a medicinal product and which did not necessarily have a causal relationship with this treatment. Please note that analyses in NGF0221 were done at the patient level, not by eye, so adverse events reported may refer to the study eye, the non-study eye, or both, indifferently.
Investigations SARS-CoV-2 test positive	4.5% 2/44 • Number of events 2 • AEs were collected from the screening visit (Day -8) until last Follow-Up visit (Week 24). An AE was defined as any untoward medical occurrence in a patient or clinical investigation patient administered a medicinal product and which did not necessarily have a causal relationship with this treatment. Please note that analyses in NGF0221 were done at the patient level, not by eye, so adverse events reported may refer to the study eye, the non-study eye, or both, indifferently.	2.5% 1/40 • Number of events 1 • AEs were collected from the screening visit (Day -8) until last Follow-Up visit (Week 24). An AE was defined as any untoward medical occurrence in a patient or clinical investigation patient administered a medicinal product and which did not necessarily have a causal relationship with this treatment. Please note that analyses in NGF0221 were done at the patient level, not by eye, so adverse events reported may refer to the study eye, the non-study eye, or both, indifferently.
Nervous system disorders Headache	6.8% 3/44 • Number of events 3 • AEs were collected from the screening visit (Day -8) until last Follow-Up visit (Week 24). An AE was defined as any untoward medical occurrence in a patient or clinical investigation patient administered a medicinal product and which did not necessarily have a causal relationship with this treatment. Please note that analyses in NGF0221 were done at the patient level, not by eye, so adverse events reported may refer to the study eye, the non-study eye, or both, indifferently.	10.0% 4/40 • Number of events 4 • AEs were collected from the screening visit (Day -8) until last Follow-Up visit (Week 24). An AE was defined as any untoward medical occurrence in a patient or clinical investigation patient administered a medicinal product and which did not necessarily have a causal relationship with this treatment. Please note that analyses in NGF0221 were done at the patient level, not by eye, so adverse events reported may refer to the study eye, the non-study eye, or both, indifferently.

Additional Information

Clinical Development & Operations

Dompé farmaceutici S.p.A.

Phone: +39 02 583831

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place