Evaluation of the Efficacy and Safety of OC-01 Nasal Spray on Signs and Symptoms of Dry Eye Disease

Multicenter, Randomized, Controlled, Double-Masked, Clinical Trial to Evaluate the Efficacy and Safety of OC-01 (Varenicline) Nasal Spray on Signs and Symptoms of Dry Eye Disease (The ONSET-2 Study)

The objective of this study is to evaluate the safety and effectiveness of OC-01 Nasal Spray as compared to placebo on signs and symptoms of dry eye disease.

Study Overview

• Status: Completed
• Conditions: Dry Eye Disease (DED)
• Intervention / Treatment: Drug: Placebo (vehicle) nasal spray; Drug: OC-01 (varenicline) nasal spray

Detailed Description

This was a Phase 3, multicenter, randomized, controlled, double-masked (including subjects, Investigators, study site personnel, and Sponsor personnel) study designed to evaluate the safety and efficacy of OC-01 (varenicline) nasal spray 0.6 mg/mL and 1.2 mg/mL in adult participants with DED. The study randomized 758 subjects at least 22 years of age with a physicians' diagnosis of DED and meeting all other study eligibility criteria to receive OC-01 (varenicline) nasal spray or placebo twice daily (BID) for 28 days with three additional long-term follow-up visits at 6 weeks, 6 months, and 12 months. Participants who terminated from the study during the treatment period were asked to complete safety assessments (if the participants agree) prior to study exit. Participants who were terminated early from the study were not replaced

• Study Type: Interventional
• Enrollment (Actual): 758
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Phoenix
  • California
    • Newport Beach, California, United States, 92663
      • New Port Beach
  • Colorado
    • Fort Collins, Colorado, United States, 80528
      • Fort Collins
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Waterbury
  • Florida
    • Delray Beach, Florida, United States, 33484
      • Delray Beach
  • Indiana
    • Indianapolis, Indiana, United States, 46290
      • Indianapolis
  • Kentucky
    • Louisville, Kentucky, United States, 40206
      • Louisville
  • Massachusetts
    • Raynham, Massachusetts, United States, 02767
      • Raynham
  • Nevada
    • Las Vegas, Nevada, United States, 89052
      • Las Vegas
  • North Carolina
    • Raleigh, North Carolina, United States, 27603
      • Raleigh
    • Shelby, North Carolina, United States, 28150
      • Shelby
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • Fargo
  • Pennsylvania
    • Cranberry Township, Pennsylvania, United States, 16066
      • Cranberry Township
  • Rhode Island
    • Warwick, Rhode Island, United States, 02842
      • Warwick
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57108
      • Sioux Falls
  • Tennessee
    • Nashville, Tennessee, United States, 37210
      • Nashville
  • Texas
    • Austin, Texas, United States, 78731
      • Austin
    • Houston, Texas, United States, 77025
      • Houston
    • San Antonio, Texas, United States, 78229
      • San Antonio
    • San Antonio, Texas, United States, 78209
      • San Antonio
  • Utah
    • Layton, Utah, United States, 84041
      • Layton
  • Virginia
    • Lynchburg, Virginia, United States, 24502
      • Lynchburg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

- Have used and/or desired to use an artificial tear substitute for dry eye symptoms within 6 months prior to Visit 1

Exclusion Criteria:

• Have had any intraocular surgery (such as cataract surgery) or extraocular surgery in either eye within three months or refractive surgery (e.g. laser-assisted in-situ keratomileusis, laser epithelial keratomileusis, photorefractive keratectomy or corneal implant) within twelve months of Visit 1.
• Have a history or presence of any ocular disorder or condition in either eye that would, in the opinion of the Investigator, likely interfere with the interpretation of the study results or participant safety such as significant corneal or conjunctival scarring; pterygium or nodular pinguecula; current ocular infection, conjunctivitis, or inflammation not associated with dry eye; anterior (epithelial) basement membrane corneal dystrophy or other clinically significant corneal dystrophy or degeneration; ocular herpetic infection; evidence of keratoconus; etc. Blepharitis not requiring treatment and mild meibomian gland disease that are typically associated with dry eye disease are allowed.
• Have a systemic condition or disease not stabilized or judged by the Investigator to be incompatible with participation in the study or with the lengthier assessments required by the study (e.g., current systemic infection, uncontrolled autoimmune disease, uncontrolled immunodeficiency disease, history of myocardial infarction or heart disease, etc.)
• Have a known hypersensitivity to any of the procedural agents or study drug components
• Have any condition or history that, in the opinion of the investigator, may interfere with study compliance, outcome measures, safety parameters, and/or the general medical condition of the subject.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo (vehicle) nasal spray	Drug: Placebo (vehicle) nasal spray; Placebo (vehicle) nasal spray
Active Comparator: OC-01 Low Dose, 0.6 mg/mL; OC-01 (varenicline) nasal spray, 0.6 mg/ML	Drug: OC-01 (varenicline) nasal spray; OC-01 (varenicline) nasal spray
Active Comparator: OC-01 High Dose, 1.2 mg/mL; OC-01 (varenicline) nasal spray, 1.2 mg/ML	Drug: OC-01 (varenicline) nasal spray; OC-01 (varenicline) nasal spray

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Subjects Who Achieve ≥10 mm Improvement in Schirmer's Test Score From Baseline at Visit 4 (Day 28)	The primary endpoint was the percentage of subjects who achieve ≥10 mm improvement in Schirmer's Test Score from baseline to 28 days in the study eye following treatment with OC-01. Schirmer's test scores from 0-35 mm where a higher score is indicative of a better outcome.	28 Days [Visit 1 (baseline) and Visit 4b (28 days)]

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in Eye Dryness Score in CAE at Week 4 at 5 Minutes	Change in Eye Dryness Score Eye from baseline in CAE at 4 Weeks at 5 minutes post treatment. Eye dryness score on a Visual Analogue Scale (VAS) from 0 (no dryness) to 100 (maximum dryness) millimeters where a lower score is indicative of a better outcome.	28 Days [Visit 1 (baseline) and Visit 4a (28 days)]
Mean Change From Baseline in Eye Dryness Score From Baseline to Day 28	Change in Eye Dryness Score Eye from baseline to 28 days. Eye dryness score on a Visual Analogue Scale (VAS) from 0 (no dryness) to 100 (maximum dryness) millimeters where a lower score is indicative of a better outcome.	28 Days [Visit 1 (baseline) and Visit 4b (28 days)]
Mean Change Form Baseline in Schirmer's Test Score From Baseline to Day 28	Change in Schirmer test score from baseline to Day 28. Schirmer's test scores from 0-35 mm where a higher score is indicative of a better outcome.	28 Days [Visit 1 (baseline) and Visit 4b (28 days)]
Mean Change From Baseline in Eye Dryness Score in the Study Eye at Week 2	Chang in Eye Dryness Score Eye from baseline to 28 days. Eye dryness score on a Visual Analogue Scale (VAS) from 0 (no dryness) to 100 (maximum dryness) millimeters where a lower score is indicative of a better otucome.	14 Days [Visit 1 (baseline) and Visit 3 (14 days)]
Mean Change From Baseline in Eye Dryness Score in the Study Eye at Week 1	Change in Eye Dryness Score Eye from baseline to 28 days. Eye dryness score on a Visual Analogue Scale (VAS) from 0 (no dryness) to 100 (maximum dryness) millimeters where a lower score is indicative of a better outcome.	7 Days [Visit 1 (baseline) and Visit 2 (7 days)]

Collaborators and Investigators

• Sponsor: Oyster Point Pharma, Inc.

Publications and helpful links

General Publications

• Nijm LM, Zhu D, Hemphill M, Blemker GL, Hendrix LH, Kabat AG, Gibson AA. Does Menopausal Status Affect Dry Eye Disease Treatment Outcomes with OC-01 (Varenicline Solution) Nasal Spray? A Post Hoc Analysis of ONSET-1 and ONSET-2 Clinical Trials. Ophthalmol Ther. 2022 Nov 18. doi: 10.1007/s40123-022-00607-7. Online ahead of print.
• Wirta D, Vollmer P, Paauw J, Chiu KH, Henry E, Striffler K, Nau J; ONSET-2 Study Group. Efficacy and Safety of OC-01 (Varenicline Solution) Nasal Spray on Signs and Symptoms of Dry Eye Disease: The ONSET-2 Phase 3 Randomized Trial. Ophthalmology. 2022 Apr;129(4):379-387. doi: 10.1016/j.ophtha.2021.11.004. Epub 2021 Nov 10.

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2019
• Primary Completion (Actual): April 10, 2020
• Study Completion (Actual): February 5, 2021

Study Registration Dates

• First Submitted: July 25, 2019
• First Submitted That Met QC Criteria: July 25, 2019
• First Posted (Actual): July 29, 2019

Study Record Updates

• Last Update Posted (Actual): November 22, 2021
• Last Update Submitted That Met QC Criteria: October 22, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Eye Diseases; Dry Eye Syndromes; Keratoconjunctivitis Sicca; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Nicotinic Agonists; Cholinergic Agonists; Varenicline
• Other Study ID Numbers: OPP-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No