Clinical trial NCT04630158: Study of Efficacy and Safety of SAF312 Eye Drops in Subjects With Post-operative Corneal Induced Chronic Pain (CICP)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Ocular Pain
Keywords: Eye pain
Dry eye like symptoms
Ocular surface pain
Corneal induced chronic pain
neuropathic eye pain
post-operative corneal induced chronic pain
CICP
corneal
corneal pain
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2020-11-16
Enrollment: 153
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: This was a Phase II randomized, double-masked, multi-center, parallel group, placebo-controlled study to evaluate the safety and efficacy of SAF312, 5 mg/mL and 15 mg/mL eye drops versus Placebo used twice-daily in both eyes for 12 weeks. The study consisted of a 12-week observation period starting from Screening Visit (Visit 1) until the Baseline/Randomization Visit (Visit 2). Subjects who met eligibility criteria at Visit 2 were randomized to one of the three treatment arms (SAF312 5 mg/mL, SAF312 15 mg/mL, Placebo) in a 1:1:1 ratio. Subjects who qualified for randomization had visits every 2 weeks for the first 4 weeks, and then monthly visits for the remainder of the 12-week treatment period.

Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline at Week 12 in Ocular Pain Severity Visual Analog Scale (VAS)
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Ocular Pain Severity Visual Analog Scale (VAS): Summary Statistics of Change From Baseline at Day 7 and Day 14
timeFrame: Baseline, Days 7 and 14
measure: Ocular Pain Frequency Visual Analog Scale (VAS): Summary Statistics of Weekly Mean Change From Baseline to Week 12
timeFrame: Baseline, Weeks 1 to 12
measure: Ocular Pain Assessment Scale (OPAS) Subscale Quality of Life: Summary Statistics of Change From Baseline to Week 12
timeFrame: Baseline, Weeks 2, 4, 8, 12
measure: Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Redness - Nasal (Oculus Dexter (OD) = Right Eye)
timeFrame: Baseline, Weeks 2, 4, 8, 12
measure: Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Redness - Nasal (Oculus Sinister (OS) = Left Eye)
timeFrame: Baseline, Weeks 2, 4, 8, 12
measure: Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Redness - Temporal (Oculus Dexter (OD) = Right Eye)
timeFrame: Baseline, Weeks 2, 4, 8, 12
measure: Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Redness - Temporal (Oculus Sinister (OS) = Left Eye)
timeFrame: Baseline, Weeks 2, 4, 8, 12
measure: Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Staining (Oculus Dexter (OD) = Right Eye)
timeFrame: Baseline, Weeks 2, 4, 8, 12
measure: Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Staining (Oculus Sinister (OS) = Left Eye)
timeFrame: Baseline, Weeks 2, 4, 8, 12
measure: Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Corneal Staining (Oculus Dexter (OD) = Right Eye)
timeFrame: Baseline, Weeks 2, 4, 8, 12
measure: Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Corneal Staining (Oculus Sinister (OS) = Left Eye)
timeFrame: Baseline, Weeks 2, 4, 8, 12
measure: Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week of Tear Production - Schirmer Test (mm) (Oculus Dexter (OD) = Right Eye)
timeFrame: Baseline, Weeks 2, 4, 8, 12
measure: Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week of Tear Production - Schirmer Test (mm) (Oculus Sinister (OS) = Left Eye)
timeFrame: Baseline, Weeks 2, 4, 8, 12
measure: Number of Participants With Treatment Emergent Adverse Events
timeFrame: 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).
measure: Ocular Treatment Emergent Adverse Events, by Primary System Organ Class (SOC) and Preferred Term (PT)
timeFrame: 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).
measure: Summary of Non-ocular Treatment Emergent Adverse Events
timeFrame: 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).
Other outcomes:
Locations:
city: Mission Hills
country: United States
facility: North Valley Eye Medical Group
state: California
city: Newport Beach
country: United States
facility: NVISION Eye Centers
state: California
city: Palo Alto
country: United States
facility: Stanford Eye Laser Center
state: California
city: San Diego
country: United States
facility: Gordon Schanzlin New Vision Inst
state: California
city: Coral Springs
country: United States
facility: Novartis Investigative Site
state: Florida
city: Jacksonville
country: United States
facility: Novartis Investigative Site
state: Florida
city: Miami
country: United States
facility: Novartis Investigative Site
state: Florida
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Needham
country: United States
facility: Boston Sight
state: Massachusetts
city: Ann Arbor
country: United States
facility: Univ of MI Kellogg Eye Center .
state: Michigan
city: Durham
country: United States
facility: Duke Univ Medical Center Ophthalmology
state: North Carolina
city: Fargo
country: United States
facility: Bergstrom Eye Research LLC
state: North Dakota
city: Philadelphia
country: United States
facility: University of Pennsylvania .
state: Pennsylvania
city: Chattanooga
country: United States
facility: Chattanooga Eye Institute
state: Tennessee
city: Memphis
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Smyrna
country: United States
facility: Advancing Vision Research LLC
state: Tennessee
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Lakeway
country: United States
facility: Lake Travis Eye and Laser Ctr
state: Texas
city: Salt Lake City
country: United States
facility: Stacy R Smith MD PC
state: Utah
city: Lynchburg
country: United States
facility: Piedmont Eye Center
state: Virginia
city: Renton
country: United States
facility: Rainier Clinical Research Center Inc .
state: Washington
city: Seattle
country: United States
facility: Periman Eye Institute
state: Washington
city: Sapporo city
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Shinagawa
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Birmingham
country: United Kingdom
facility: Novartis Investigative Site
state: West Midlands
city: Newcastle Upon Tyne
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: