Chronic Ocular Pain Clinical Trial
Official title:
A 12-week Parallel Group, Randomized, Placebo-controlled, Double-blinded, Multi-center Study to Evaluate Efficacy and Safety of 2 Concentrations of SAF312 Eye Drops (5 mg/ml and 15 mg/ml) Used Twice-daily in the Treatment of Post-operative Corneal Induced Chronic Pain (CICP) Following Photorefractive Keratectomy (PRK) or Laser-assisted in Situ Keratomileusis (LASIK) Surgeries
| Verified date | March 2024 |
| Source | Novartis |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
The study was designed to demonstrate the safety and efficacy of two dose concentrations of SAF312 eye drops (5 mg/mL and 15 mg/mL) in subjects with CICP persisting at least for 4 months after refractive or cataract surgery and chronicity confirmed during the observational period. The study also determined the optimal dose to carry forward for further development.
| Status | Completed |
| Enrollment | 153 |
| Est. completion date | June 8, 2023 |
| Est. primary completion date | June 7, 2023 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Key Inclusion Criteria: - Subjects who have undergone refractive surgery (i.e., PRK, LASIK, LASEK, RK, or SMILE) in both eyes or cataract surgery in both eyes, with or without refractive enhancement in one or both eyes, =4 months prior to Screening Visit and experiencing persistent ocular surface pain since the surgery, and have been seen by an ophthalmologist or optometrist at least once with complaint of continued ocular pain since surgery. - Subjects who demonstrate a = 60% reduction in ocular pain within 5 minutes after instillation of a single topical ocular anesthetic drop at Screening Visit. At Baseline - Subjects with an average pain severity VAS score of = 30 mm based on Daily eDiary for the last 7 days prior to Baseline Visit. - Subjects who have reported pain severity >10 mm based on Daily eDiary for > 50% of the days of the observational period (Screening) Key Exclusion Criteria: - Use of nerve growth factor eye drops within 14 days of the Screening Visit - Seasonal allergic conjunctivitis, or other acute or seasonal ocular diagnosis that are active at the time of Screening or would be active during the course of the study. - Any history of ocular herpes simplex virus or herpes zoster virus infection, or other severe ocular conditions such as graft versus host disease, Stevens-Johnson syndrome or sarcoidosis. - Presence of any ocular infection (bacterial, viral, or fungal) within 30 days prior to Screening. - Chronic topical ocular medications (ie. cyclosporine, lifitegrast) initiated <6 months prior to Screening Visit, or any anticipated change during the study. - Use of ocular or nasal corticosteroids within 30 days of Screening Visit. - Use of neuromodulatory medications (eg, gabapentin, pregabalin) or opioid use for non-ocular pain within 30 days of Screening Visit. - Chronic medications (both over the counter and prescription) that have not been stable for at least 30 days prior to Screening Visit, or any anticipated change in the chronic medication regimen. - Subjects requiring hospitalization within 6 months prior to screening for severe psychiatric disorders (e.g. psychosis, schizophrenia, mania, depression) or major psychiatric illness. |
| Country | Name | City | State |
|---|---|---|---|
| Japan | Novartis Investigative Site | Sapporo city | Hokkaido |
| Japan | Novartis Investigative Site | Shinagawa | Tokyo |
| United Kingdom | Novartis Investigative Site | Birmingham | West Midlands |
| United Kingdom | Novartis Investigative Site | Newcastle Upon Tyne | |
| United States | Univ of MI Kellogg Eye Center . | Ann Arbor | Michigan |
| United States | Tufts Medical Center | Boston | Massachusetts |
| United States | Chattanooga Eye Institute | Chattanooga | Tennessee |
| United States | Novartis Investigative Site | Coral Springs | Florida |
| United States | Duke Univ Medical Center Ophthalmology | Durham | North Carolina |
| United States | Bergstrom Eye Research LLC | Fargo | North Dakota |
| United States | Novartis Investigative Site | Houston | Texas |
| United States | Novartis Investigative Site | Houston | Texas |
| United States | Novartis Investigative Site | Houston | Texas |
| United States | Novartis Investigative Site | Jacksonville | Florida |
| United States | Lake Travis Eye and Laser Ctr | Lakeway | Texas |
| United States | Piedmont Eye Center | Lynchburg | Virginia |
| United States | Novartis Investigative Site | Memphis | Tennessee |
| United States | Novartis Investigative Site | Miami | Florida |
| United States | North Valley Eye Medical Group | Mission Hills | California |
| United States | Boston Sight | Needham | Massachusetts |
| United States | NVISION Eye Centers | Newport Beach | California |
| United States | Stanford Eye Laser Center | Palo Alto | California |
| United States | University of Pennsylvania . | Philadelphia | Pennsylvania |
| United States | Rainier Clinical Research Center Inc . | Renton | Washington |
| United States | Stacy R Smith MD PC | Salt Lake City | Utah |
| United States | Gordon Schanzlin New Vision Inst | San Diego | California |
| United States | Periman Eye Institute | Seattle | Washington |
| United States | Advancing Vision Research LLC | Smyrna | Tennessee |
| Lead Sponsor | Collaborator |
|---|---|
| Novartis Pharmaceuticals |
United States, Japan, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Change From Baseline at Week 12 in Ocular Pain Severity Visual Analog Scale (VAS) | The pain severity Visual Analogue Scale (VAS) was completed by the subject using an electronic diary. A vertical mark was placed on the horizontal scoring line (anchored with 'No Pain' on the left and 'Very Severe' pain on the right) to score the severity of ocular pain over the past 24 hours, with a range from 0 (min) to 100 (max). Higher scores indicate higher pain severity. A negative change from baseline is a positive outcome. | Baseline, Week 12 | |
| Secondary | Ocular Pain Severity Visual Analog Scale (VAS): Summary Statistics of Change From Baseline at Day 7 and Day 14 | The pain severity Visual Analogue Scale (VAS) was completed by the subject using an electronic diary. A vertical mark was placed on the horizontal scoring line (anchored with 'No Pain' on the left and 'Very Severe' pain on the right) to score the severity of ocular pain over the past 24 hours, with a range from 0 (min) to 100 (max). Higher scores indicate higher pain severity. A negative change from baseline is a positive outcome. | Baseline, Days 7 and 14 | |
| Secondary | Ocular Pain Frequency Visual Analog Scale (VAS): Summary Statistics of Weekly Mean Change From Baseline to Week 12 | The pain frequency Visual Analogue Scale (VAS) was completed by the subject using an electronic diary. A vertical mark was placed on the horizontal scoring line (anchored with 'No Pain' on the left and 'Very Frequent' pain on the right) to score the frequency of ocular pain over the past 24 hours, with a range from 0 (min) to 100 (max). Higher scores indicate higher pain frequency. A negative change from baseline is a positive outcome. | Baseline, Weeks 1 to 12 | |
| Secondary | Ocular Pain Assessment Scale (OPAS) Subscale Quality of Life: Summary Statistics of Change From Baseline to Week 12 | Each question in the Ocular Pain Assessment Survey (OPAS) quality of life subscale was scored by the subject on a line marked from 0 (not at all) to 10 (completely) that described how much pain interfered with or affected a particular activity (max score= 10/question). A higher score suggests a higher impact by pain on a particular activity. A negative change from baseline is a positive outcome. There are 7 questions in total regarding Quality of Life. The average score of the 7 Quality of Life questions is reported (mean (SD)). | Baseline, Weeks 2, 4, 8, 12 | |
| Secondary | Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Redness - Nasal (Oculus Dexter (OD) = Right Eye) | Conjunctival redness in each of two regions (nasal and temporal) was graded on a scale from 0 to 5 using the McMonnies conjunctival redness photographic scale (max score=5/region). Higher scores suggest higher degrees of redness (worsening). A negative change from baseline is a positive outcome. | Baseline, Weeks 2, 4, 8, 12 | |
| Secondary | Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Redness - Nasal (Oculus Sinister (OS) = Left Eye) | Conjunctival redness in each of two regions (nasal and temporal) was graded on a scale from 0 to 5 using the McMonnies conjunctival redness photographic scale (max score=5/region). Higher scores suggest higher degrees of redness (worsening). A negative change from baseline is a positive outcome. | Baseline, Weeks 2, 4, 8, 12 | |
| Secondary | Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Redness - Temporal (Oculus Dexter (OD) = Right Eye) | The pain severity Visual Analogue Scale (VAS) was completed by the subject using an electronic diary. A vertical mark was placed on the horizontal scoring line (anchored with 'No Pain' on the left and 'Very Severe' pain on the right) to score the severity of ocular pain over the past 24 hours, with a range from 0 (min) to 100 (max). Higher scores indicate higher pain severity. A negative change from baseline is a positive outcome. A negative change from baseline is a positive outcome. | Baseline, Weeks 2, 4, 8, 12 | |
| Secondary | Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Redness - Temporal (Oculus Sinister (OS) = Left Eye) | Conjunctival redness in each of two regions (nasal and temporal) was graded on a scale from 0 to 5 using the McMonnies conjunctival redness photographic scale (max score=5/region). Higher scores suggest higher degrees of redness (worsening). A negative change from baseline is a positive outcome. | Baseline, Weeks 2, 4, 8, 12 | |
| Secondary | Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Staining (Oculus Dexter (OD) = Right Eye) | The degree of lissamine conjunctival staining in two regions (temporal and nasal) was graded on a scale from 0 to 4 (max score = 8/eye). Higher scores suggest higher degrees of corneal staining (worsening). A negative change from baseline is a positive outcome. | Baseline, Weeks 2, 4, 8, 12 | |
| Secondary | Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Staining (Oculus Sinister (OS) = Left Eye) | The degree of lissamine conjunctival staining in two regions (temporal and nasal) was graded on a scale from 0 to 4 (max score = 8/eye). Higher scores suggest higher degrees of corneal staining (worsening). A negative change from baseline is a positive outcome. | Baseline, Weeks 2, 4, 8, 12 | |
| Secondary | Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Corneal Staining (Oculus Dexter (OD) = Right Eye) | The degree of corneal fluorescein staining in each of five regions (superior, inferior, nasal, temporal, and central) was graded on a scale from 0 to 4 (max score=20/eye). Higher scores suggest higher degrees of corneal staining (worsening). A negative change from baseline is a positive outcome. | Baseline, Weeks 2, 4, 8, 12 | |
| Secondary | Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Corneal Staining (Oculus Sinister (OS) = Left Eye) | The degree of corneal fluorescein staining in each of five regions (superior, inferior, nasal, temporal, and central) was graded on a scale from 0 to 4 (max score=20/eye). Higher scores suggest higher degrees of corneal staining (worsening). A negative change from baseline is a positive outcome. | Baseline, Weeks 2, 4, 8, 12 | |
| Secondary | Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week of Tear Production - Schirmer Test (mm) (Oculus Dexter (OD) = Right Eye) | The Schirmer's test was performed without anesthetic. Tear secretion was measured in millimeters based on the length of strip wetted by tears (max score =35 mm/eye). Lower values indicate lower relative amounts of tear secretion (worsening). A negative change from baseline is a positive outcome. | Baseline, Weeks 2, 4, 8, 12 | |
| Secondary | Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week of Tear Production - Schirmer Test (mm) (Oculus Sinister (OS) = Left Eye) | The Schirmer's test was performed without anesthetic. Tear secretion was measured in millimeters based on the length of strip wetted by tears (max score =35 mm/eye). Lower values indicate lower relative amounts of tear secretion (worsening). A negative change from baseline is a positive outcome. | Baseline, Weeks 2, 4, 8, 12 | |
| Secondary | Number of Participants With Treatment Emergent Adverse Events | An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. | Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months). | |
| Secondary | Ocular Treatment Emergent Adverse Events, by Primary System Organ Class (SOC) and Preferred Term (PT) | An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study.
MedDRA Version 26.0 was used for the reporting of adverse events. |
Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months). | |
| Secondary | Summary of Non-ocular Treatment Emergent Adverse Events | An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. | Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months). |