A Phase 3 interventional study of Oxervate and Vehicle in Dry Eye, sponsored by Dompé Farmaceutici S.p.A. Completed at 10 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-06-07.
Sponsored by Dompé Farmaceutici S.p.A · Phase 3, Interventional, and Treatment
Primary objectives
Secondary objectives
This is a 4 week phase III, multicenter, double-masked, vehicle-controlled study to evaluate safety and efficacy of cenegermin ophthalmic solution at 20 mcg/mL solution versus vehicle, in patients with severe Sjogren's dry eye disease.
During the screening all procedures for inclusion and exclusion were performed. From the day of screening the patients stopped any kind of further treatment, except commercially available preservative free artificial tears provided by Sponsor.
At the end of the wash out period, patients meeting the entry criteria for this study were randomized 1:1 and treated for 4 weeks with either cenegermin ophthalmic solution 20 mcg/mL TID or vehicle TID.
During the 4 weeks of masked treatment only the administration of IMP was allowed.
During the follow up period, the patient could administer additional artificial tear eye drops, provided by Sponsor, only if strictly needed, and should document in the patient's diary the number of additional drops administered for each eye.
Patients were then followed up for efficacy and safety endpoints until week 16 and for safety endpoints until week 24.
The total duration of the study was 25 weeks including 1 week of screening.
1,292 studies on the registry are indexed under Dry Eye Syndromes; 192 are open to participants now.
This study's enrollment of 104 is above the median of 60 across 1,077 interventional studies indexed under Dry Eye Syndromes.
Browse Dry Eye Syndromes studies →Dompé Farmaceutici S.p.A is the lead sponsor of 51 studies on the registry; 4 are open to participants now.
Of its 18 completed or terminated interventional studies of FDA-regulated products, 18 (100%) have results posted.
Counted across the registry records on this site, refreshed daily.
Patients with severe Sjögren's dry eye disease characterized by the following clinical features:
Exclusion Criteria:
Females of childbearing potential (those who are not surgically sterilized or post-menopausal for at least 1 year) are excluded from participation in the study if they meet any one of the following conditions:
During the entire course of and 30 days after the study treatment periods
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.
Drug: Oxervate
One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours).
Other: Vehicle
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).
Also known as: Cenegermin
Vehicle will be instilled with the same scheme of the test product
Also known as: Reference product
Number of Patients Reaching a Value of Schirmer I Test (Without Anaesthesia) >10mm/5min at Week 4
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.
Time frame: at week 4
Change From Baseline in Symptoms Questionnaire (SANDE) Global Score at Week 12
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.
Time frame: at week 12
Key Secondary Outcome: Number of Patients Reaching a Value of Schirmer I Test (Without Anaesthesia) > 10mm/5min 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.
Time frame: at Week 8
Key Secondary Outcome: Change From Baseline in Symptoms Assessment in Dry Eye (SANDE) Score for Frequency at Week 12
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.
Time frame: At week 12
Key Secondary Outcome: Change From Baseline in Symptoms Assessment in Dry Eye (SANDE) Score for Severity at Week 12
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.
Time frame: at Week 12
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
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.
Time frame: At Weeks 12 and 4
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
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.
Time frame: at Weeks 12 and 4
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
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.
Time frame: at Weeks 12 and 4
Key Secondary Outcome: Change From Baseline in Cornea and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) 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.
Time frame: At weeks 4, 8, 12
Key Secondary Outcome: Change From Baseline in Tear Film Break-Up Time (TFBUT) at Week 4, Week 8, Week 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.
Time frame: At weeks 4, 8, 12
Change From Baseline in Schirmer I Test (Without Anaesthesia) [Time Frame: Week 4, 8, 12 and 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.
Time frame: Week 4, 8, 12 and 16
Change From Baseline in Cornea and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) at Week 16
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.
Time frame: at Week 16
Change From Baseline in Tear Film Break-Up Time (TFBUT) at Week 16
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.
Time frame: at week 16
Change From Baseline in Symptoms Questionnaire (SANDE) Global Score at Week 8, Week 12, 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.
Time frame: at Week 8, Week 12, Week 16
Change From Baseline in Symptoms Questionnaire (SANDE) Score for Frequency at Week 8, Week 12, 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.
Time frame: at Week 8, Week 12, Week 16
Change From Baseline in Symptoms Assessment in Dry Eye (SANDE) Score for Severity at Week 8, Week 12 and 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.
Time frame: at Week 8, week 12 and week 16
Number of Patients Who Experienced a Worsening in Symptoms Scores (SANDE) and/or NEI Score > = 50% at Week 4
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.
Time frame: at week 4
Change From Baseline in Quality of Life Module Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Weeks 8 and 16
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.
Time frame: At weeks 8 and 16
Change From Baseline in "Symptom Bother Module" Measured by "Impact of Dry Eye on Everyday Life [IDEEL]" Questionnaire at Week 8 and Week 16
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.
Time frame: at Week 8 and Week 16
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
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.
Time frame: at Week 8 and Week 16
Incidence and Frequency of TEAEs, Assessed Throughout the Study.
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.
Time frame: From Screening to Visit 7 (follow-up, week 24)
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.
| Milestone | Oxervate | Vehicle |
|---|---|---|
| Started | 52 | 52 |
| Randomized but not treated | 0 | 1 |
| Safety population (saf) | 52 | 51 |
| Full analysis set population (fas) | 52 | 51 |
| Per protocol population (pp) | 46 | 47 |
| Prematurely study discontinued | 2 | 3 |
| Completed | 50 | 49 |
| Not completed | 2 | 3 |
| Withdrew: Withdrawal of consent | 1 | 1 |
| Withdrew: Lost to follow-up | 1 | 1 |
| Withdrew: Documented disease progression | 0 | 1 |
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.
| Participants | Oxervate (FAS) | Vehicle (FAS) |
|---|---|---|
| Number of Patients Reaching a Value of Schirmer I Test (Without Anaesthesia) >10mm/5min at Week 4 | 19 | 2 |
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.
| score on a scale | Oxervate (FAS) | Vehicle (FAS) |
|---|---|---|
| Change From Baseline in Symptoms Questionnaire (SANDE) Global Score at Week 12 | -29.5 (-42.126 to -16.930) | -25 (-37.009 to -12.926) |
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.
| Participants | Oxervate (FAS) | Vehicle (FAS) |
|---|---|---|
| Key Secondary Outcome: Number of Patients Reaching a Value of Schirmer I Test (Without Anaesthesia) > 10mm/5min at Week 8 | 18 | 2 |
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.
| score on a scale | Oxervate (FAS) | Vehicle (FAS) |
|---|---|---|
| Key Secondary Outcome: Change From Baseline in Symptoms Assessment in Dry Eye (SANDE) Score for Frequency at Week 12 | -24.546 (-38.261 to -10.831) | -21.793 (-34.944 to -8.643) |
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.
| score on a scale | Oxervate (FAS) | Vehicle (FAS) |
|---|---|---|
| Key Secondary Outcome: Change From Baseline in Symptoms Assessment in Dry Eye (SANDE) Score for Severity at Week 12 | -31.445 (-43.795 to -19.095) | -26.713 (-38.538 to -14.887) |
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.
| score on a scale | Oxervate (FAS) | Vehicle (FAS) |
|---|---|---|
| Impact on daily activities - week 12 | 13.301 (6.267 to 20.335) | 9.223 (2.437 to 16.008) |
| Emotional impact due to dry eye - week 12 | 16.069 (7.476 to 24.661) | 10.519 (2.185 to 18.853) |
| Impact on work due to dry eye - week 12 | 18.619 (9.309 to 27.928) | 15.144 (6.371 to 23.916) |
| Impact on daily activities - week 4 | 11.524 (5.207 to 17.842) | 9.364 (3.354 to 15.374) |
| Emotional impact due to dry eye - week 4 | 14.385 (6.840 to 21.930) | 11.955 (4.732 to 19.177) |
| Impact on work due to dry eye - week 4 | 17.591 (8.213 to 26.969) | 14.291 (5.787 to 22.795) |
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.
| score on a scale | Oxervate (FAS) | Vehicle (FAS) |
|---|---|---|
| Satisfaction with Treatment Effectiveness - week 12 | 12.733 (1.180 to 24.285) | 16.938 (5.033 to 28.844) |
| Treatment- Related Bother / Inconvenience - week 12 | 6.482 (-0.877 to 13.842) | 4.239 (-2.942 to 11.420) |
| Satisfaction with Treatment Effectiveness - week 4 | 13.879 (2.071 to 25.686) | 14.428 (3.246 to 25.609) |
| Treatment- Related Bother / Inconvenience - week 4 | 9.505 (2.772 to 16.237) | 8.432 (1.840 to 15.025) |
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.
| score on a scale | Oxervate (FAS) | Vehicle (FAS) |
|---|---|---|
| week 12 | -16.323 (-23.582 to -9.064) | -7.533 (-14.574 to -0.493) |
| week 4 | -10.241 (-16.924 to -3.557) | -9.435 (-15.876 to -2.995) |
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.
| score on a scale | Oxervate (FAS) | Vehicle (FAS) |
|---|---|---|
| Week 4 | -4.107 (-5.723 to -2.490) | -2.588 (-4.118 to -1.059) |
| Week 8 | -4.442 (-6.145 to -2.739) | -2.668 (-4.298 to -1.038) |
| Week 12 | -3.714 (-5.522 to -1.905) | -2.490 (-4.222 to -0.758) |
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.
| seconds | Oxervate (FAS) | Vehicle (FAS) |
|---|---|---|
| Week 4 | 1.808 (0.437 to 3.178) | 0.167 (-1.144 to 1.479) |
| Week 8 | 2.010 (0.579 to 3.441) | 0.876 (-0.502 to 2.255) |
| Week 12 | 1.973 (0.588 to 3.358) | 0.613 (-0.715 to 1.941) |
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.
| millimeters | Oxervate (FAS) | Vehicle (FAS) |
|---|---|---|
| week 4 | 5.4 ± 6.6 | 0.8 ± 2.7 |
| week 8 | 4.9 ± 6.6 | 1.4 ± 2.9 |
| week 12 | 3.8 ± 5.2 | 1.4 ± 4.1 |
| week 16 | 3.6 ± 5.1 | 1.7 ± 4.8 |
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.
| score on a scale | Oxervate (FAS) | Vehicle (FAS) |
|---|---|---|
| Change From Baseline in Cornea and Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales) at Week 16 | -3.3 ± 4.6 | -2.7 ± 5.8 |
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.
| seconds | Oxervate (FAS) | Vehicle (FAS) |
|---|---|---|
| Change From Baseline in Tear Film Break-Up Time (TFBUT) at Week 16 | 1.3 ± 3.1 | 0.4 ± 2.8 |
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.
| score on a scale | Oxervate (FAS) | Vehicle (FAS) |
|---|---|---|
| week 8 | -26.0 ± 20.1 | -15.2 ± 22.1 |
| week 12 | -20.4 ± 22.0 | -15.7 ± 26.7 |
| week 16 | -15.2 ± 20.5 | -16.0 ± 25.2 |
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.
| score on a scale | Oxervate (FAS) | Vehicle (FAS) |
|---|---|---|
| week 8 | -27.1 ± 22.5 | -15.9 ± 24.4 |
| week 12 | -17.9 ± 23.4 | -15.7 ± 28.2 |
| week 16 | -12.5 ± 21.2 | -16.1 ± 25.6 |
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.
| score on a scale | Oxervate (FAS) | Vehicle (FAS) |
|---|---|---|
| week 8 | -23.7 ± 20.8 | -14.4 ± 21.6 |
| week 12 | -21.2 ± 23.5 | -15.7 ± 26.5 |
| week 16 | -16.6 ± 23.6 | -16.1 ± 25.9 |
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.
| Participants | Oxervate (FAS) | Vehicle (FAS) |
|---|---|---|
| Number of Patients Who Experienced a Worsening in Symptoms Scores (SANDE) and/or NEI Score > = 50% at Week 4 | 4 | 11 |
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.
| score on a scale | Oxervate (FAS) | Vehicle (FAS) |
|---|---|---|
| Impact on Daily Activities - week 8 | 14.6 ± 18.8 | 6.5 ± 23.2 |
| Emotional Impact due to Dry Eye - week 8 | 18.4 ± 21.9 | 10.3 ± 22.9 |
| Impact on Work due to Dry Eye - week 8 | 17.7 ± 25.7 | 9.5 ± 25.9 |
| Impact on Daily Activities - week 16 | 15.1 ± 20.8 | 9.7 ± 21.1 |
| Emotional Impact due to Dry Eye - week 16 | 19.0 ± 23.1 | 11.5 ± 23.3 |
| Impact on Work due to Dry Eye - week 16 | 20.9 ± 24.2 | 9.3 ± 26.7 |
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.
| score on a scale | Oxervate (FAS) | Vehicle (FAS) |
|---|---|---|
| week 8 | -19.5 ± 20.3 | -6.9 ± 19.2 |
| week 16 | -18.6 ± 19.4 | -11.1 ± 22.3 |
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.
| score on a scale | Oxervate (FAS) | Vehicle (FAS) |
|---|---|---|
| Satisfaction with Treatment Effectiveness - week 8 | 17.7 ± 31.0 | 7.7 ± 36.4 |
| Treatment- Related Bother / Inconvenience - week 8 | 16.6 ± 21.1 | 2.7 ± 28.1 |
| Satisfaction with Treatment Effectiveness - week 16 | 13.4 ± 28.7 | 1.2 ± 35.9 |
| Treatment- Related Bother / Inconvenience - week 16 | 13.3 ± 23.6 | 5.3 ± 27.3 |
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.
| Participants | Oxervate (SAF) | Vehicle (SAF) |
|---|---|---|
| TEAE - Ophtalmic | 35 | 13 |
| TEAE - Non Ophtalmic | 16 | 9 |
| Severe TEAE - Ophtamic | 5 | 1 |
| Severe TEAE - Non Opthalmic | 2 | 1 |
| Serious TEAE - Ophtalmic | 1 | 0 |
| Serious TEAE - Non Ophtalmic | 2 | 1 |
| non-serious TEAE | 37 | 15 |
| Adverse Drug Reaction (ADR) - Ophtalmic | 34 | 8 |
| Adverse Drug Reaction - Non Ophtalmic | 4 | 2 |
| Serious ADR | 1 | 0 |
| TEAE leading to IMP discontinuation | 2 | 1 |
| TEAE leading to study discontinuation | 0 | 1 |
| TEAE leading to death | 0 | 0 |
Collected over Adverse events were collected from screening visit (Day -8) to follow up (Day 168+/- 7 days). Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Oxervate (SAF) | 0/52 (0%) | 2/52 (3.8%) | 37/52 (71.2%) |
| Vehicle (SAF) | 0/51 (0%) | 1/51 (2%) | 15/51 (29.4%) |
| Event | Oxervate (SAF) | Vehicle (SAF) |
|---|---|---|
| ArthropathyMusculoskeletal and connective tissue disorders | 0/52 | 1/51 |
| Visual acuity reducedEye disorders | 1/52 | 0/51 |
| Pancreatitis acuteGastrointestinal disorders | 1/52 | 0/51 |
| HypertransaminasaemiaHepatobiliary disorders | 1/52 | 0/51 |
| BacteraemiaInfections and infestations | 1/52 | 0/51 |
| Event | Oxervate (SAF) | Vehicle (SAF) |
|---|---|---|
| Eye pain - MildEye disorders | 16/52 | 3/51 |
| Eye pain - ModerateEye disorders | 7/52 | 2/51 |
| Eyelid pain - MildEye disorders | 6/52 | 0/51 |
| Eyelid pain - ModerateEye disorders | 5/52 | 0/51 |
| Eye pruritus - MildEye disorders | 1/52 | 4/51 |
| Foreign body sensation in eyes - ModerateEye disorders | 2/52 | 3/51 |
| Eye pain - SevereEye disorders | 3/52 | 0/51 |
| Eye irritation - ModerateEye disorders | 1/52 | 2/51 |
| Eye pruritus - ModerateEye disorders | 0/52 | 2/51 |
| Ocular hyperaemia - MildEye disorders | 1/52 | 2/51 |
The Full Analysis Set (FAS) population included all patients who were randomized and received at least one dose of the investigational product.
| Age, Categorical(Participants) | Oxervate (FAS) | Vehicle (FAS) | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 39 | 34 | 73 |
| >=65 years | 13 | 17 | 30 |
| Age, Continuous(years) | Oxervate (FAS) | Vehicle (FAS) | Total |
|---|---|---|---|
| Mean | 55.3 ± 13.47 | 58.7 ± 14.10 | 57.0 ± 13.83 |
| Sex: Female, Male(Participants) | Oxervate (FAS) | Vehicle (FAS) | Total |
|---|---|---|---|
| Female | 50 | 47 | 97 |
| Male | 2 | 4 | 6 |
| Race (NIH/OMB)(Participants) | Oxervate (FAS) | Vehicle (FAS) | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 3 | 3 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 1 | 1 |
| White | 43 | 39 | 82 |
| More than one race | 1 | 1 | 2 |
| Unknown or Not Reported | 8 | 7 | 15 |
| Region of Enrollment(participants) | Oxervate (FAS) | Vehicle (FAS) | Total |
|---|---|---|---|
| United States | 25 | 28 | 53 |
| Italy | 27 | 23 | 50 |
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Dompé Farmaceutici S.p.A