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

Primary Purpose

Chronic Ocular Pain

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
SAF312 Placebo
SAF312
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Ocular Pain focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Experimental

Experimental

Arm Label

SAF312 Placebo

SAF312 dose 1

SAF312 dose 2

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

Change in mean pain severity Visual Analog Scale
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
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
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
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
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
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
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.
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
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.

Full Information

First Posted
November 12, 2020
Last Updated
July 7, 2023
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT04630158
Brief Title
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

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
April 21, 2021 (Actual)
Primary Completion Date
June 7, 2023 (Actual)
Study Completion Date
June 8, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double-blinded
Allocation
Randomized
Enrollment
153 (Actual)

8. Arms, Groups, and Interventions

Arm Title
SAF312 Placebo
Arm Type
Placebo Comparator
Arm Description
Randomized to a 1:1:1 topical eye drops, twice daily
Arm Title
SAF312 dose 1
Arm Type
Experimental
Arm Description
Randomized to a 1:1:1 topical eye drops, twice daily
Arm Title
SAF312 dose 2
Arm Type
Experimental
Arm Description
Randomized to a 1:1:1 topical eye drops, twice daily
Intervention Type
Other
Intervention Name(s)
SAF312 Placebo
Other Intervention Name(s)
Artificial tears
Intervention Description
Topical ocular, suspension eye drops,
Intervention Type
Drug
Intervention Name(s)
SAF312
Intervention Description
Topical ocular, suspension eye drops
Primary Outcome Measure Information:
Title
Change in mean pain severity Visual Analog Scale
Description
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.
Time Frame
84 days
Secondary Outcome Measure Information:
Title
Change in pain severity Visual Analog Scale
Description
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.
Time Frame
Baseline, Day 7 and Day 14
Title
Change in pain frequency Visual Analog Scale
Description
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.
Time Frame
Baseline, Week 12
Title
Change in Ocular Pain Assessment Scale (OPAS) sub-scale Quality of Life
Description
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.
Time Frame
Baseline, Week 12
Title
Change in ocular surface parameters as assessed by the corneal fluorescein staining
Description
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).
Time Frame
Baseline, Week 12
Title
Change in ocular surface parameters as assessed by lissamine staining
Description
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).
Time Frame
Baseline, Week 12
Title
Change in ocular surface parameters as assessed by Schirmer's testing
Description
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).
Time Frame
Baseline, Week 12
Title
Change in ocular surface parameters as evaluated by the investigator using the McMonnies redness photographic scale.
Description
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).
Time Frame
Baseline, Week 12
Title
Comparison of adverse events rates between active and placebo
Description
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.
Time Frame
Baseline, End of Study (Day 88)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Mission Hills
State/Province
California
ZIP/Postal Code
91345
Country
United States
Facility Name
Novartis Investigative Site
City
Newport Beach
State/Province
California
ZIP/Postal Code
92660
Country
United States
Facility Name
Novartis Investigative Site
City
Palo Alto
State/Province
California
ZIP/Postal Code
94303
Country
United States
Facility Name
Novartis Investigative Site
City
San Diego
State/Province
California
ZIP/Postal Code
92122
Country
United States
Facility Name
Novartis Investigative Site
City
Coral Springs
State/Province
Florida
ZIP/Postal Code
33067
Country
United States
Facility Name
Novartis Investigative Site
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32256
Country
United States
Facility Name
Novartis Investigative Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Novartis Investigative Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Novartis Investigative Site
City
Needham
State/Province
Massachusetts
ZIP/Postal Code
02494
Country
United States
Facility Name
Novartis Investigative Site
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48105
Country
United States
Facility Name
Novartis Investigative Site
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Novartis Investigative Site
City
Fargo
State/Province
North Dakota
ZIP/Postal Code
58103
Country
United States
Facility Name
Novartis Investigative Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Novartis Investigative Site
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37411
Country
United States
Facility Name
Novartis Investigative Site
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38119
Country
United States
Facility Name
Novartis Investigative Site
City
Smyrna
State/Province
Tennessee
ZIP/Postal Code
37167
Country
United States
Facility Name
Novartis Investigative Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77025
Country
United States
Facility Name
Novartis Investigative Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Novartis Investigative Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77074
Country
United States
Facility Name
Novartis Investigative Site
City
Lakeway
State/Province
Texas
ZIP/Postal Code
78738
Country
United States
Facility Name
Novartis Investigative Site
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84117
Country
United States
Facility Name
Novartis Investigative Site
City
Lynchburg
State/Province
Virginia
ZIP/Postal Code
24502
Country
United States
Facility Name
Novartis Investigative Site
City
Renton
State/Province
Washington
ZIP/Postal Code
98057
Country
United States
Facility Name
Novartis Investigative Site
City
Seattle
State/Province
Washington
ZIP/Postal Code
98119
Country
United States
Facility Name
Novartis Investigative Site
City
Sapporo city
State/Province
Hokkaido
ZIP/Postal Code
060 8648
Country
Japan
Facility Name
Novartis Investigative Site
City
Shinagawa
State/Province
Tokyo
ZIP/Postal Code
141-0022
Country
Japan
Facility Name
Novartis Investigative Site
City
Birmingham
State/Province
West Midlands
ZIP/Postal Code
B75 6QW
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Newcastle upon Tyne
ZIP/Postal Code
NE1 4LP
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.
IPD Sharing URL
https://www.clinicalstudydatarequest.com/

Learn more about this trial

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

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