Study of Efficacy and Safety of SAF312 Eye Drops in Subjects With Post-operative Corneal Induced Chronic Pain (CICP)

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04630158

Collaborator

(none)

150

Enrollment

Locations

Arms

24.1

Anticipated Duration (Months)

3.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study is designed to demonstrate the safety and efficacy of two dose concentrations of SAF312 eye drops (dose 1 and dose 2) in subjects with CICP persisting at least for 4 months after refractive or cataract surgery and chronicity confirmed during the observational period. The study will also determine the optimal dose to carry forward for further development.

Condition or Disease	Intervention/Treatment	Phase
Chronic Ocular Pain	Other: SAF312 Placebo Drug: SAF312	Phase 2

Detailed Description

This study is a Phase 2 randomized, double-blinded, multi-center, parallel group, placebo-controlled evaluation of 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. Eligible subjects will 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 at least 4 months prior to Screening, and have been suffering from chronic ocular pain as a result of their surgery. Eligible patients must also demonstrate chronicity of the pain at Baseline Visit as described in inclusion criteria. Overall approximately 150 subjects will be enrolled in the study and randomized to one of 3 study arms in 1:1:1 ratio

Study Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Double-blinded

Primary Purpose:

Treatment

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

Actual Study Start Date :

Apr 21, 2021

Anticipated Primary Completion Date :

Apr 24, 2023

Anticipated Study Completion Date :

Apr 24, 2023

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: SAF312 Placebo Randomized to a 1:1:1 topical eye drops, twice daily	Other: SAF312 Placebo Topical ocular, suspension eye drops, Other Names: Artificial tears
Experimental: SAF312 dose 1 Randomized to a 1:1:1 topical eye drops, twice daily	Drug: SAF312 Topical ocular, suspension eye drops
Experimental: SAF312 dose 2 Randomized to a 1:1:1 topical eye drops, twice daily	Drug: SAF312 Topical ocular, suspension eye drops

Arm

Intervention/Treatment

Placebo Comparator: SAF312 Placebo

Randomized to a 1:1:1 topical eye drops, twice daily

Other: SAF312 Placebo

Topical ocular, suspension eye drops,

Other Names:

Artificial tears

Experimental: SAF312 dose 1

Randomized to a 1:1:1 topical eye drops, twice daily

Drug: SAF312

Topical ocular, suspension eye drops

Experimental: SAF312 dose 2

Randomized to a 1:1:1 topical eye drops, twice daily

Drug: SAF312

Topical ocular, suspension eye drops

Outcome Measures

Primary Outcome Measures

Change in mean pain severity Visual Analog Scale [84 days]
To demonstrate the efficacy of at least 1 of 2 concentrations of SAF312 (dose 1 or dose 2) with superiority to placebo in reducing ocular pain severity. The pain severity Visual Analogue Scale (VAS) is completed by the subject using an electronic diary. A vertical mark is 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 (max score=100). Higher scores indicate higher pain severity.

Secondary Outcome Measures

Change in pain severity Visual Analog Scale [Baseline, Day 7 and Day 14]
To evaluate additional efficacy of 2 concentrations of SAF312 vs placebo (eg., time to pain severity improvement). The pain severity Visual Analogue Scale (VAS) is completed by the subject using an electronic diary. A vertical mark is 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 (max score=100). Higher scores indicate higher pain severity.
Change in pain frequency Visual Analog Scale [Baseline, Week 12]
To evaluate additional efficacy of 2 concentrations of SAF312 vs placebo (eg., time to pain frequency improvement). The pain frequency Visual Analogue Scale (VAS) is completed by the subject using an electronic diary. A vertical mark is placed on the horizontal scoring line (anchored with 'Rarely' on the left and 'All the Time' on the right) to score the frequency of ocular pain over the past 24 hours (max score=100). Higher scores indicate higher pain frequency.
Change in Ocular Pain Assessment Scale (OPAS) sub-scale Quality of Life [Baseline, Week 12]
To evaluate additional efficacy of 2 concentrations of SAF312 vs placebo (e.g., time to improvement in quality of life). Each question in the Ocular Pain Assessment Survey (OPAS) quality of life subscale is scored by the subject on a line marked from 0 (not at all) to 10 (completely) that describes how much pain has interfered with or affected a particular activity (max score= 10/question). A higher score suggests a higher impact by pain on a particular activity.
Change in ocular surface parameters as assessed by the corneal fluorescein staining [Baseline, Week 12]
To evaluate if SAF312 has negative effects to the ocular surface after prolonged TRPV1 inhibition. The degree of corneal fluorescein staining in each of five regions (superior, inferior, nasal, temporal, and central) is graded on a scale from 0 to 4 (max score=20/eye). Higher scores suggest higher degrees of corneal staining (worsening).
Change in ocular surface parameters as assessed by lissamine staining [Baseline, Week 12]
To evaluate if SAF312 has negative effects to the ocular surface after prolonged TRPV1 inhibition. The degree of lissamine conjunctival staining in two regions (temporal and nasal) is graded on a scale from 0 to 4 (max score = 8/eye). Higher scores suggest higher degrees of corneal staining (worsening).
Change in ocular surface parameters as assessed by Schirmer's testing [Baseline, Week 12]
To evaluate if SAF312 has negative effects to the ocular surface after prolonged TRPV1 inhibition. The Schirmer's test will be performed without anesthetic. Tear secretion is 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).
Change in ocular surface parameters as evaluated by the investigator using the McMonnies redness photographic scale. [Baseline, Week 12]
To evaluate if SAF312 has negative effects to the ocular surface after prolonged TRPV1 inhibition. Conjunctival redness in each of two regions (nasal and temporal) is 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).
Comparison of adverse events rates between active and placebo [Baseline, End of Study (Day 88)]
To evaluate the safety of 2 concentrations of SAF312 (dose 1 and dose 2). Ocular and non-ocular adverse events will be summarized separately. Separate summaries also will be provided for study treatment related adverse events, death, serious adverse events, and other significant adverse events leading to discontinuation. Higher rates of adverse events in the active group compared to the placebo may suggest potential safety signals.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Bakersfield	California	United States	93309
2	Novartis Investigative Site	Los Angeles	California	United States	90025
3	Novartis Investigative Site	Mission Hills	California	United States	91345
4	Novartis Investigative Site	Newport Beach	California	United States	92660
5	Novartis Investigative Site	Palo Alto	California	United States	94303
6	Novartis Investigative Site	San Diego	California	United States	92122
7	Novartis Investigative Site	Coral Springs	Florida	United States	33067
8	Novartis Investigative Site	Fort Lauderdale	Florida	United States	33309
9	Novartis Investigative Site	Jacksonville	Florida	United States	32256
10	Novartis Investigative Site	Miami	Florida	United States	33136
11	Novartis Investigative Site	Atlanta	Georgia	United States	30328
12	Novartis Investigative Site	Atlanta	Georgia	United States	30339
13	Novartis Investigative Site	Baltimore	Maryland	United States	21201
14	Novartis Investigative Site	Boston	Massachusetts	United States	02111
15	Novartis Investigative Site	Needham	Massachusetts	United States	02494
16	Novartis Investigative Site	Ann Arbor	Michigan	United States	48105
17	Novartis Investigative Site	Kansas City	Missouri	United States	64155
18	Novartis Investigative Site	Las Vegas	Nevada	United States	98102
19	Novartis Investigative Site	Durham	North Carolina	United States	27710
20	Novartis Investigative Site	Fargo	North Dakota	United States	58103
21	Novartis Investigative Site	Fargo	North Dakota	United States	58103
22	Novartis Investigative Site	Oklahoma City	Oklahoma	United States	73104
23	Novartis Investigative Site	Philadelphia	Pennsylvania	United States	19104
24	Novartis Investigative Site	Chattanooga	Tennessee	United States	37411
25	Novartis Investigative Site	Maryville	Tennessee	United States	37803
26	Novartis Investigative Site	Memphis	Tennessee	United States	38119
27	Novartis Investigative Site	Nashville	Tennessee	United States	37215
28	Novartis Investigative Site	Smyrna	Tennessee	United States	37167
29	Novartis Investigative Site	Bellaire	Texas	United States	77401
30	Novartis Investigative Site	Houston	Texas	United States	77025
31	Novartis Investigative Site	Houston	Texas	United States	77030
32	Novartis Investigative Site	Lakeway	Texas	United States	78738
33	Novartis Investigative Site	San Antonio	Texas	United States	78240
34	Novartis Investigative Site	Salt Lake City	Utah	United States	84117
35	Novartis Investigative Site	Lynchburg	Virginia	United States	24502
36	Novartis Investigative Site	Renton	Washington	United States	98057
37	Novartis Investigative Site	Seattle	Washington	United States	98119
38	Novartis Investigative Site	Ichikawa	Chiba	Japan	272-8513
39	Novartis Investigative Site	Shinagawa	Tokyo	Japan	141-0022
40	Novartis Investigative Site	Birmingham	West Midlands	United Kingdom	B75 6QW
41	Novartis Investigative Site	London		United Kingdom	EC1V 2PD
42	Novartis Investigative Site	Newcastle upon Tyne		United Kingdom	NE1 4LP