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| ID | Type | Description | Link |
|---|---|---|---|
| 2021-003346-21 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Oxervate | Experimental | 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. |
|
| Vehicle | Placebo Comparator | One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Oxervate | Drug | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | at week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | From Screening to Visit 7 (follow-up, week 24) |
Inclusion Criteria:
Male or female aged ≥ 18 years
Patients with a confirmed diagnosis of Sjögren's syndrome or other autoimmune disease known to induce Sjögren's Dry Eye Disease (DED).
Patients with severe Sjögren's dry eye disease characterized by the following clinical features:
The same eye (eligible eye) must fulfill all the above criteria
Patients diagnosed with severe Sjögren's dry eye disease at least 3 months before enrolment
Best corrected distance visual acuity (BCDVA) score of ≥ 0.1 decimal units (20/200 Snellen value) in each eye at the time of study enrolment
If a female of childbearing potential, have a negative urine pregnancy test and use a highly effective method to avoid pregnancy for the duration of the trial and 30 days after the study treatment period. Males of reproductive potential should use effective contraception during treatment and 30 days after the study treatment period.
Only patients who satisfy all Informed Consent requirements may be included in the study. The patient and/or his/her legal representative must read, sign and date the Informed Consent document before any study-related procedures are performed. The Informed Consent Form signed by patients and/or legal representative must have been approved by the IRB/IEC for the current study
Patients must have the ability and willingness to comply with study procedures.
Exclusion Criteria:
Inability to speak and understand the local language sufficiently to understand the nature of the study, to provide written informed consent, and to allow the completion of all study assessments
Evidence of an active ocular infection, in either eye
Presence of any other ocular disorder or condition requiring topical medication during the entire duration of study in either eye
History of severe systemic allergy or of ocular allergy (including seasonal conjunctivitis) or chronic conjunctivitis and/or keratitis other than dry eye
Intraocular inflammation defined as Tyndall score >0
History of malignancy in the last 5 years
Systemic disease not stabilized within 1 month before Screening Visit (e.g. diabetes with glycemia out of range, thyroid malfunction) or judged by the investigator to be incompatible with the study (e.g. current systemic infections) or with a condition incompatible with the frequent assessment required by the study
Patient had a serious adverse reaction or significant hypersensitivity to any drug or chemically related compounds or had a clinically significant allergy to drugs, foods, amide local anesthetics or other materials including commercial artificial tears (in the opinion of the investigator).
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
Any concurrent medical condition, that in the judgment of the PI, might interfere with the conduct of the study, confound the interpretation of the study results, or endanger the patient's well-being
Use of topical cyclosporine, or topical ophthalmic treatments of the same class, within 14 days of screening visit (day -8)
Use of topical corticosteroids, lifitegrast, autologous serum tears in either eye during the study (previous use not an exclusion criteria but must be discontinued at the screening visit)
Contact lenses, True Tear device, moisture goggles, sutureless amniotic membrane or punctum plug use during the study (previous use not an exclusion criteria but must be discontinued at the screening visit)
History of drug addiction or alcohol abuse in the last 2 years
Any prior ocular surgery (including refractive, palpebral and cataract surgery) if within 90 days before the screening visit
Participation in a clinical trial with a new active substance during the past 3 months
Participation in another clinical trial study at the same time as the present study.
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| Name | Affiliation | Role |
|---|---|---|
| Flavio Mantelli, MD | Dompé Farmaceutici | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Lugene Eye Institute - Glendale Office | Glendale | California | 91204 | United States | ||
| David Wirta, M.D. & Associates |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Oxervate | One drop of cenegermin 20 mcg/mL (rhNGF 20 mcg/mL) in the pharmaceutical form of ophthalmic sterile solution was instilled in both eyes three times daily (TID), every six hours. Oxervate: Oxervate®, an ophthalmic solution containing cenegermin 20 mcg/mL, which is a recombinant human Nerve Growth Factor (rhNGF); one drop of the test product will be instilled in both eyes three times daily (TID). |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 26, 2022 | Jan 23, 2024 |
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double-masked study
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| Vehicle | Other | Vehicle will be instilled with the same scheme of the test product |
|
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| 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | at Week 8 and Week 16 |
| Newport Beach |
| California |
| 92663 |
| United States |
| The Johns Hopkins University | Baltimore | Maryland | 21218 | United States |
| Tufts University School of Medicine (TUSM) - New England Eye Center/Tufts Medical Center - Boston | Boston | Massachusetts | 02111 | United States |
| Houston Eye Associates HEA - Gramercy Location | Houston | Tennessee | 77025 | United States |
| Toyos Clinic - Nashville | Nashville | Tennessee | 37215 | United States |
| Virginia Eye Consultants (VEC) - Norfolk Office | Norfolk | Virginia | 23502 | United States |
| AOU Gaspare Rodolico - Ospedale San Marco | Catania | 95123 | Italy |
| Università degli Studi di Milano - Ospedale San Giuseppe - UO Oculistica | Milan | 20123 | Italy |
| AOU Policlinico Umberto I - Dipartimento Organi di Senso - Clinica Oculistica | Roma | 00161 | Italy |
| FG001 | Vehicle | One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product |
| Randomized But Not Treated |
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| Safety Population (SAF) |
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| Full Analysis Set Population (FAS) |
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| Per Protocol Population (PP) |
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| Prematurely Study Discontinued |
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| COMPLETED | study completed |
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| NOT COMPLETED |
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The Full Analysis Set (FAS) population included all patients who were randomized and received at least one dose of the investigational product.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Oxervate (FAS) | One drop of cenegermin 20 mcg/mL (rhNGF 20 mcg/mL) in the pharmaceutical form of ophthalmic sterile solution was instilled in both eyes three times daily (TID), every six hours. Oxervate: Oxervate®, an ophthalmic solution containing cenegermin 20 mcg/mL, which is a recombinant human Nerve Growth Factor (rhNGF); one drop of the test product will be instilled in both eyes three times daily (TID). |
| BG001 | Vehicle (FAS) | One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | 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. | The Full Analysis Set (FAS) population consisted of all patients who were randomized and received at least one dose of the investigational product. The number of participants effectively analyzed was 51 in Cenegermin group and 50 in the Vehicle group. In fact 1 patient in Cenegermin group and 1 patient in vehicle group had imputed values of missing data. | Posted | Count of Participants | Participants | at week 4 |
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| Primary | 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. | The Full Analysis Set (FAS) population consisted of all patients who were randomized and received at least one dose of the investigational product. Please note that adjusted means are reported. | Posted | Mean | 95% Confidence Interval | score on a scale | at week 12 |
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| Secondary | 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. | The Full Analysis Set (FAS) population consisted of all patients who were randomized and received at least one dose of the investigational product. The number of participants with no imputed values for Schirmer I test at Week 8 was 49 in the IMP group and 49 in the vehicle group. | Posted | Count of Participants | Participants | at Week 8 |
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| Secondary | 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. | The Full Analysis Set (FAS) population consisted of all patients who were randomized and received at least one dose of the investigational product. The number of participants effectively analyzed was 49 in Cenegermin group and 49 in the Vehicle group. In fact 3 patients in Cenegermin group and 2 patients in vehicle group had imputed values of missing data via a MI approach. | Posted | Mean | 95% Confidence Interval | score on a scale | At week 12 |
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| Secondary | 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. | The Full Analysis Set (FAS) population consisted of all patients who were randomized and received at least one dose of the investigational product. The number of participants effectively analyzed was 49 in Cenegermin group and 49 in the Vehicle group at Week 8 and Week 12, and 50 in Cenegermin group and 49 in Vehicle group at Week 16. | Posted | Mean | 95% Confidence Interval | score on a scale | at Week 12 |
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| Secondary | 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. | The Full Analysis Set (FAS) population consisted of all patients randomized, who received at least one dose of IP. 3 patients in Cenegermin group and 2 patients in vehicle group had imputed values of missing data for Impact on Daily Activities and Emotional Impact due to dry eye. For Impact on work due to dry eye the number of participants considered in the model was 30 in Cenegermin group and 34 in the Vehicle group, of which 4 and 6 had imputed values. | Posted | Least Squares Mean | 95% Confidence Interval | score on a scale | At Weeks 12 and 4 |
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| Secondary | 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. | The Full Analysis Set (FAS) population consisted of all patients who were randomized and received at least one dose of the investigational product. 3 patients in Cenegermin group and 4 patients in vehicle group had imputed values of missing data for Satisfaction with Treatment Effectiveness. For Treatment- Related Bother / Inconvenience, 4 patients in Cenegermin group and 3 patients in vehicle group had imputed values of missing data. | Posted | Least Squares Mean | 95% Confidence Interval | score on a scale | at Weeks 12 and 4 |
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| Secondary | 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. | The Full Analysis Set (FAS) population consisted of all patients who were randomized and received at least one dose of the investigational product. 3 patients in Cenegermin group and 2 patients in vehicle group had imputed values of missing data. | Posted | Least Squares Mean | 95% Confidence Interval | score on a scale | at Weeks 12 and 4 |
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| Secondary | 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. | The Full Analysis Set (FAS) population consisted of all patients who were randomized and received at least one dose of the investigational product. 3 patients in Cenegermin group and 2 patients in vehicle group had imputed values of missing data via a multiple imputation approach. | Posted | Least Squares Mean | 95% Confidence Interval | score on a scale | At weeks 4, 8, 12 |
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| Secondary | 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. | The Full Analysis Set (FAS) population consisted of all patients who were randomized and received at least one dose of the investigational product. 3 patients in Cenegermin group and 2 patients in vehicle group had imputed values of missing data using a MI approach. | Posted | Least Squares Mean | 95% Confidence Interval | seconds | At weeks 4, 8, 12 |
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| Secondary | 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. | The Full Analysis Set (FAS) population consisted of all patients who were randomized and received at least one dose of the investigational product. The actual number of participants effectively analyzed was 51 in the IMP group and 50 in the vehicle group at Week 4, 49 in both IMP and vehicle group at Week 8 and at Week 12, and 50 in the IMP group and 49 in the vehicle group at Week 16. | Posted | Least Squares Mean | Standard Deviation | millimeters | Week 4, 8, 12 and 16 |
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| Secondary | 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. | The Full Analysis Set (FAS) population consisted of all patients who were randomized and received at least one dose of the investigational product. The number of participants effectively analyzed at weeks 8 and 12 was 49 in Cenegermin group and 49 in the Vehicle group. At week 4 the participants analyzed were 51 in Cenegermin and 50 in Vehicle group. At week 16, the number of participants analyzed were 50 in Cenegermin and 49 in Vehicle group. | Posted | Least Squares Mean | Standard Deviation | score on a scale | at Week 16 |
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| Secondary | 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. | The Full Analysis Set (FAS) population consisted of all patients who were randomized and received at least one dose of the investigational product. he number of participants effectively analyzed at weeks 8 and 12 was 49 in Cenegermin group and 49 at the Vehicle group. At week 4 the participants analyzed were 51 in Cenegermin and 50 in Vehicle group. At week 16, the number of participants analyzed were 50 in Cenegermin group and 49 in the Vehicle group. | Posted | Least Squares Mean | Standard Deviation | seconds | at week 16 |
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| Secondary | 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. | The Full Analysis Set (FAS) population consisted of all patients who were randomized and received at least one dose of the investigational product. The number of participants effectively analyzed was 49 in Cenegermin group and 49 in the Vehicle group at Week 8 and Week 12, and 50 in Cenegermin group and 49 in Vehicle group at Week 16. | Posted | Least Squares Mean | Standard Deviation | score on a scale | at Week 8, Week 12, Week 16 |
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| Secondary | 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. | The Full Analysis Set (FAS) population consisted of all patients who were randomized and received at least one dose of the investigational product. The number of participants effectively analyzed was 49 in Cenegermin group and 49 in the Vehicle group at Week 8 and Week 12, and 50 in Cenegermin group and 49 in Vehicle group at Week 16 | Posted | Least Squares Mean | Standard Deviation | score on a scale | at Week 8, Week 12, Week 16 |
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| Secondary | 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. | The Full Analysis Set (FAS) population consisted of all patients who were randomized and received at least one dose of the investigational product. The number of participants effectively analyzed was 49 in Cenegermin group and 49 in the Vehicle group at Week 8 and Week 12, and 50 in Cenegermin group and 49 in Vehicle group at Week 16 | Posted | Least Squares Mean | Standard Deviation | score on a scale | at Week 8, week 12 and week 16 |
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| Secondary | 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. | The Full Analysis Set (FAS) population consisted of all patients who were randomized and received at least one dose of the investigational product. | Posted | Count of Participants | Participants | at week 4 |
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| Secondary | 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. | The Full Analysis Set (FAS) consisted of all patients randomized and dosed with at least one dose of the IP. The # of pts actually analyzed for Impact on Daily Activities and Emotional Impact due to Dry Eye was: Week 4: n=51 Cenegermin (C) n=50 Vehicle (V); Weeks 8 and 12: n=49 in both groups Week 16: n=50 C n=49 V. For Impact on work due to dry eye the No of pts actually analyzed was: Weeks 4 and 8 n= 24 C n= 30 V Week 12 n=23 C n=28 V Week 16: n= 23 C n=29 V | Posted | Mean | Standard Deviation | score on a scale | At weeks 8 and 16 |
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| Secondary | 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. | The Full Analysis Set (FAS) population consisted of all patients who were randomized and received at least one dose of the investigational product. The number of participants effectively analyzed was 51 in Cenegermin group and 50 in the Vehicle group at Week 4, 49 in both treatment groups at Week 8 and Week 12, 50 in Cenegermin group and 49 in Vehicle group at Week 16. | Posted | Mean | Standard Deviation | score on a scale | at Week 8 and Week 16 |
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| Secondary | 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. | The FAS consisted of all patients randomized and dosed with at least one dose of the IP. The # of pts effectively analyzed for Impact on Daily Activities and Emotional Impact due to Dry Eye was: for Satisfaction with Treatment Effectiveness section: Wk 4: n=48 C n=44 V; Wk 8: n=47 C n=44 V Wk 12 n=48 C n=44 V Wk 16: n=48 C n=42 V. For T-Related Bother / Inconvenience section: Wk 4 n= 48 C n= 44 V Wk 8: n=46 both groups Wk 12 n=47 C n=46 V Wk 16: n= 48 C n=46 V | Posted | Mean | Standard Deviation | score on a scale | at Week 8 and Week 16 |
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| Other Pre-specified | 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. | The SAF population consisted of all randomized patients who received at least one dose of the investigational product. SAF set was analysed according to the actual treatment received. The SAF population was used to present results on safety data. | Posted | Count of Participants | Participants | From Screening to Visit 7 (follow-up, week 24) |
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Adverse events were collected from screening visit (Day -8) to follow up (Day 168+/- 7 days)
Adverse Event (AE) was defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Oxervate (SAF) | One drop of cenegermin 20 mcg/mL (rhNGF 20 mcg/mL) in the pharmaceutical form of ophthalmic sterile solution was instilled in both eyes three times daily (TID), every six hours. Oxervate: Oxervate®, an ophthalmic solution containing cenegermin 20 mcg/mL, which is a recombinant human Nerve Growth Factor (rhNGF); one drop of the test product will be instilled in both eyes three times daily (TID). | 0 | 52 | 2 | 52 | 37 | 52 |
| EG001 | Vehicle (SAF) | One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product | 0 | 51 | 1 | 51 | 15 | 51 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Visual acuity reduced | Eye disorders | MedDRA 24.0 | Systematic Assessment |
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| Pancreatitis acute | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
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| Hypertransaminasaemia | Hepatobiliary disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Bacteraemia | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
| |
| Arthropathy | Musculoskeletal and connective tissue disorders | MedDRA 24.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia - Mild | Blood and lymphatic system disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Deafness bilateral - Mild | Ear and labyrinth disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Vertigo positional - Moderate | Ear and labyrinth disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Asthenopia - Mild | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Chalazion - Mild | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Chalazion - Moderate | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Conjunctival hyperaemia - Mild | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Corneal epithelium defect - Mild | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Corneal oedema - Moderate | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Dry eye - Mild | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Dry eye - Moderate | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Erythema of eyelid - Mild | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Eye discharge - Mild | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Eye discharge - Moderate | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Eye inflammation - Moderate | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Eye irritation - Mild | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Eye irritation - Moderate | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Eye pain - Mild | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Eye pain - Moderate | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Eye pain - Severe | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Eye pruritus - Mild | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Eye pruritus - Moderate | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Eyelid disorder - Mild | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Eyelid margin crusting - Mild | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Eyelid pain - Mild | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Eyelid pain - Moderate | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Eyelid pain - Severe | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Eyelid ptosis - Moderate | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Eyelid sensory disorder - Mild | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Foreign body sensation in eyes - Mild | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Foreign body sensation in eyes - Moderate | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Keratopathy - Moderate | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Lacrimation increased - Mild | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Ocular hyperaemia - Mild | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Periorbital pain - Mild | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Periorbital pain - Moderate | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Photophobia - Mild | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Photophobia - Moderate | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Photophobia - Severe | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Punctate keratitis - Moderate | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Swelling of eyelid - Moderate | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Ulcerative keratitis - Mild | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Vision blurred - Mild | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Vision blurred - Moderate | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Visual acuity reduced - Moderate | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Visual field defect - Mild | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Visual impairment - Moderate | Eye disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Pancreatitis acute - Moderate | Gastrointestinal disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Fatigue - Severe | General disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Instillation site pain - Mild | General disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Bile duct stone - Moderate | Hepatobiliary disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Hypertransaminasaemia - Moderate | Hepatobiliary disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Seasonal allergy - Moderate | Immune system disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Bacteraemia - Moderate | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
| |
| COVID-19 - Mild | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
| |
| COVID-19 - Moderate | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
| |
| Coronavirus infection - Mild | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
| |
| Genital herpes simplex -Mild | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
| |
| Otitis media - Mild | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
| |
| Sinusitis - Mild | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
| |
| Upper respiratory tract infection - Mild | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
| |
| Urinary tract infection - Mild | Infections and infestations | MedDRA 24.0 | Systematic Assessment |
| |
| Arthropod bite - Mild | Injury, poisoning and procedural complications | MedDRA 24.0 | Systematic Assessment |
| |
| Meniscus injury - Moderate | Injury, poisoning and procedural complications | MedDRA 24.0 | Systematic Assessment |
| |
| Skin laceration - Moderate | Injury, poisoning and procedural complications | MedDRA 24.0 | Systematic Assessment |
| |
| Spinal compression fracture - Mild | Injury, poisoning and procedural complications | MedDRA 24.0 | Systematic Assessment |
| |
| Blood thyroid stimulating hormone increased - Mild | Investigations | MedDRA 24.0 | Systematic Assessment |
| |
| Arthralgia - Moderate | Musculoskeletal and connective tissue disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Arthropathy - Severe | Musculoskeletal and connective tissue disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Back pain - Mild | Musculoskeletal and connective tissue disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Fibromyalgia - Moderate | Musculoskeletal and connective tissue disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Pain in jaw - Moderate | Musculoskeletal and connective tissue disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Rheumatoid arthritis - Mild | Musculoskeletal and connective tissue disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Scleroderma - Moderate | Musculoskeletal and connective tissue disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Sjogren's syndrome - Moderate | Musculoskeletal and connective tissue disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Systemic lupus erythematosus - Moderate | Musculoskeletal and connective tissue disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Aura - Mild | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Headache - Mild | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Headache - Moderate | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Headache - Severe | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
| |
| Migraine - Mild | Nervous system disorders | MedDRA 24.0 | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Development & Operations | Dompé farmaceutici SpA | +39 02 583831 | clinical.trials@dompe.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 14, 2022 | Jan 23, 2024 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D015352 | Dry Eye Syndromes |
| ID | Term |
|---|---|
| D007766 | Lacrimal Apparatus Diseases |
| D005128 | Eye Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000647429 | cenegermin |
Not provided
Not provided
Not provided
| >=65 years |
|
| Male |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Italy |
|
| Superiority |
The following null hypothesis is defined on this endpoint: the number of patients reaching a value of Schirmer I test (without anaesthesia) >10mm/5min at week 4 in cenegermin (rhNGF) is lower or equal than control. The null hypothesis is rejected if the associated primary analysis p-value is lower than 0.025. |
| OG001 | Vehicle (FAS) | One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product |
|
|
|
|
|
|
| OG001 | Vehicle (FAS) | One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product |
|
|
|
| OG001 | Vehicle (FAS) | One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product |
|
|
|
| OG001 | Vehicle (FAS) | One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product |
|
|
|
| OG001 | Vehicle (FAS) | One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product |
|
|
|
| Vehicle (FAS) |
One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product |
|
|
|
| OG001 | Vehicle (FAS) | One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product |
|
|
|
One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product |
|
|
|
One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours).
Vehicle: Vehicle will be instilled with the same scheme of the test product
|
|
|
| OG001 | Vehicle (FAS) | One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product |
|
|
|
| OG001 | Vehicle (FAS) | One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product |
|
|
|
| OG001 | Vehicle (FAS) | One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product |
|
|
|
| OG001 | Vehicle (FAS) | One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product |
|
|
|
| OG001 | Vehicle (FAS) | One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product |
|
|
|
|
|
|
| OG001 | Vehicle (FAS) | One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product |
|
|
|
| OG001 | Vehicle (FAS) | One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product |
|
|
|
| OG001 | Vehicle (FAS) | One drop of vehicle ophthalmic solution was instilled in both eyes TID (every six hours). Vehicle: Vehicle will be instilled with the same scheme of the test product |
|
|
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
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