Effect of NOV03 on Signs and Symptoms of Dry Eye Disease Associated With Meibomian Gland Dysfunction (Mojave Study)

A Phase 3, Multi-Center, Randomized, Double-Masked, Saline-Controlled Trial to Evaluate the Effect of NOV03 on Signs and Symptoms of Dry Eye Disease Associated With Meibomian Gland Dysfunction (Mojave Study)

The objectives of this trial are to assess the efficacy, safety, and tolerability of NOV03 ophthalmic solution in comparison to a saline control for the treatment of the signs and symptoms of Dry Eye Disease (DED) associated with Meibomian Gland Dysfunction (MGD).

Study Overview

• Status: Completed
• Conditions: Dry Eye Disease
• Intervention / Treatment: Drug: NOV03; Drug: Saline Solution

• Study Type: Interventional
• Enrollment (Actual): 620
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Bausch Site 206
  • California
    • Garden Grove, California, United States, 92843
      • Bausch Site 202
    • Hemet, California, United States, 92545
      • Bausch Site 221
    • Inglewood, California, United States, 90301
      • Bausch Site 214
    • Murrieta, California, United States, 92562
      • Bausch Site 226
    • Santa Ana, California, United States, 92705
      • Bausch Site 213
    • Westminster, California, United States, 92683
      • Bausch site 236
  • Colorado
    • Grand Junction, Colorado, United States, 81501
      • Bausch Site 225
  • Florida
    • Delray Beach, Florida, United States, 33484
      • Bausch Site 211
  • Georgia
    • Morrow, Georgia, United States, 30260
      • Bausch Site 204
  • Illinois
    • Chicago, Illinois, United States, 60616
      • Bausch Site 209
    • Hoffman Estates, Illinois, United States, 60169
      • Bausch Site 218
  • Kansas
    • Overland Park, Kansas, United States, 66210
      • Bausch Site 230
  • Kentucky
    • Louisville, Kentucky, United States, 40220
      • Bausch Site 207
  • Maryland
    • Havre De Grace, Maryland, United States, 21078
      • Bausch Site 228
  • Minnesota
    • Bloomington, Minnesota, United States, 55431
      • Bausch Site 231
  • Missouri
    • Saint Louis, Missouri, United States, 63128
      • Bausch Site 229
    • Saint Louis, Missouri, United States, 63131
      • Bausch Site 224
    • Washington, Missouri, United States, 63090
      • Bausch Site 217
  • New York
    • Rochester, New York, United States, 14618
      • Bausch Site 208
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Bausch Site 210
    • High Point, North Carolina, United States, 27262
      • Bausch Site 233
    • Southern Pines, North Carolina, United States, 28387
      • Bausch site 232
  • Ohio
    • Cincinnati, Ohio, United States, 45247
      • Bausch Site 201
    • Cleveland, Ohio, United States, 44115
      • Bausch Site 216
    • Columbus, Ohio, United States, 43215
      • Bausch Site 223
  • Tennessee
    • Nashville, Tennessee, United States, 37215
      • Bausch Site 215
  • Texas
    • Austin, Texas, United States, 78731
      • Bausch Site 235
    • Cedar Park, Texas, United States, 78613
      • Bausch Site 219
    • League City, Texas, United States, 77573
      • Bausch Site 212
    • San Antonio, Texas, United States, 78215
      • Bausch Site 222
    • San Antonio, Texas, United States, 78209
      • Bausch Site 234
    • San Antonio, Texas, United States, 78230
      • Bausch Site 203
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Bausch Site 220
  • Washington
    • Seattle, Washington, United States, 98119
      • Bausch Site 227

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Was at least 18 years of age at the time of consent.
2. Provided written informed consent.
3. Had a subject-reported history of DED in both eyes for at least 6 months prior to Visit 0.
4. Had a TFBUT ≤5 seconds at Visit 0 and Visit 1.
5. Had an OSDI score ≥25 at Visit 0 and Visit 1.
6. Had an unanesthetized Schirmer's test I score ≥5 mm at Visit 0 and Visit 1.
7. Had MGD defined as total MGD score ≥3 at Visit 0 and Visit 1 (secretion of 5 central glands on the lower eyelid was evaluated, and each was scored from 0-3: 0 = normal; 1 = thick/yellow, whitish, particulate; 2 = paste; 3 = none/occluded). Total score ranged from 0-15.
8. Had a tCFS score between 4 and 11 (ie, sum of inferior, superior, central, nasal, and temporal) according to the NEI scale at Visit 0 and Visit 1.
9. Had at least one eye (the same eye) that satisfied all criteria for 4, 6, 7, and 8 above at Visit 0 and Visit 1.
10. Was able and willing to follow instructions, including participation in all trial assessments and visits.

Exclusion Criteria:

A subject was excluded from participating in the study if he or she met any of the following criteria:

1. Had been randomized in NVU-002 or NVU-003 study or had participated in the NVU-004 open-label extension (OLE) study.
2. Had any clinically significant ocular surface slit-lamp findings at Visit 0 and Visit 1 and/or in the opinion of the Investigator had any findings that may have interfered with trial parameters, including eye trauma or history of eye trauma or anterior membrane dystrophy.
3. Had a history of Stevens-Johnson syndrome.
4. Had active blepharitis or lid margin inflammation that required any topical antibiotics or topical steroids within last 30 days prior to Visit 0 or would have likely required such treatment during the trial. Any other lid margin therapy such as lid scrubs, lid wipes, warm compresses, systemic antibiotics (such as tetracyclines) and oral supplements for treatment of ocular conditions had to be stable within the last 30 days prior to Visit 1 and was to be maintained throughout the trial.
5. Had had a LipiFlow procedure, intense pulse light procedure or any kind of other procedure affecting meibomian glands within 6 months prior to Visit 1.
6. Had abnormal lid anatomy that caused incomplete eyelid closure, including entropion and ectropion, or floppy lid syndrome that exposed parts of the conjunctiva or impaired the blinking function of the eye.
7. Had received or removed a permanent punctum plug within 3 months (6 months for dissolvable punctum plugs) prior to Visit 1 or was expected to receive a punctum plug or removal of a punctum plug, or had a punctum plug expected to be dissolved during the trial.
8. Had DED secondary to scarring, irradiation, alkali burns, cicatricial pemphigoid, or destruction of conjunctival goblet cells (as with vitamin A deficiency).
9. Had an ocular or periocular malignancy.
10. Had a corneal epithelial defect or had significant confluent staining or filaments anywhere on the cornea.
11. Had a history of herpetic keratitis.
12. Had active ocular allergies or ocular allergies that were expected to be active during the trial period.
13. Was diagnosed with an active ocular or systemic infection (bacterial, viral, or fungal), including fever requiring treatment with antibiotics.
14. Had worn contact lenses within 1 month of Visit 0 or anticipated using contact lenses during the trial.
15. Had used any eye drops and/or TrueTearTM device (intranasal tear neurostimulator) within 24 hours before Visit 1.
16. Had undergone intraocular surgery or ocular laser surgery within the previous 6 months or had any planned ocular and/or lid surgeries over the trial period.
17. Was a family member living in the same household as another subject who was randomized into Study 904 or NVU-003 or participated in NVU-004 OLE.
18. Was a clinical site employee directly involved in the management, administration, or support of this trial or was an immediate family member of the same.
19. Was a woman who was pregnant, nursing or planning a pregnancy.
20. Was unwilling to submit to a urine pregnancy test at Visit 0, Visit 1 and Visit 4 (or early termination visit) if of childbearing potential. Non-childbearing potential was defined as a woman who was permanently sterilized (eg, had a hysterectomy or bilateral tubal ligation or bilateral oophorectomy) or was post-menopausal (without menses for 12 consecutive months).
21. Was a woman of childbearing potential who was not using an acceptable means of birth control; acceptable methods of contraception included: hormonal (oral, implantable, injectable, or transdermal contraceptives); mechanical (spermicide in conjunction with a barrier such as a diaphragm or condom); intrauterine device; or surgical sterilization of partner. For non-sexually active females, abstinence could have been regarded as an adequate method of birth control; however, if the subject became sexually active during the trial, she had to agree to use adequate birth control as defined above for the remainder of the trial.
22. Had an uncontrolled systemic disease in the opinion of the Investigator.
23. Had a known allergy and/or sensitivity to the investigational drug or saline components.
24. Had active ocular or periocular rosacea that in the judgement of the Investigator interfered with the trial (eg, clinically relevant lid induration).
25. Had a pterygium in any eye.
26. Was currently enrolled in an investigational drug or device study or had used an investigational drug or device within 60 days of Visit 1.
27. Had used any topical ocular steroids treatments, topical cyclosporine, lifitegrast, serum tears or topical anti-glaucoma medication within 60 days prior to Visit 0.
28. Had used any oral medications known to cause ocular drying (eg, antihistamines, antidepressants, etc.) on a non-stable regimen within 1 month prior to Visit 0 or was expected to be unstable during the trial.
29. Had corrected VA worse than or equal to logarithm of the minimum angle of resolution (LogMAR), +0.7 as assessed with Early Treatment Diabetic Retinopathy Study (ETDRS) charts in both eyes at Visit 0 and Visit 1.
30. Had a condition or was in a situation (including language barrier) that the Investigator felt put the subject at significant risk, may have confounded the trial results, or may have interfered significantly with the subject's participation in the trial.
31. Had a history of isotretinoin (eg, Accutane, Myorisan, Claravis, Amnesteem) use.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NOV03; 100% perfluorohexyloctane 4 times daily (QID)	Drug: NOV03; 100% perfluorohexyloctane
Placebo Comparator: Saline solution; 0.6% sodium chloride solution 4 times daily (QID)	Drug: Saline Solution; 0.6% sodium chloride solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Total Corneal Fluorescein Staining Score (NEI Scale) in the Study Eye at Day 57	The National Eye Institute (NEI) scale relies on a chart that divides the cornea into five sections (central, superior, temporal, nasal, and inferior) and assigns a value from 0 (absent) to 3 (severe) to each section, based on the amount, size, and confluence of the punctate keratitis, for a maximum total score of 15 points (sum of scores for each section).	Assessed at Day 57
Change From Baseline in Dryness Score (Visual Analogue Scale [VAS] Severity of Dryness) at Day 57	Study staff will ask participants to rate their severity of ocular dryness (both eyes simultaneously) by placing a vertical mark on a horizontal line to indicate the level of discomfort (0 corresponds to "no dryness" and 100% corresponds to "maximal dryness").	Assessed at Day 57

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Dryness Score (Visual Analogue Scale [VAS] Severity of Dryness) at Day 15	Study staff will ask participants to rate their severity of ocular dryness (both eyes simultaneously) by placing a vertical mark on a horizontal line to indicate the level of discomfort (0 corresponds to "no dryness" and 100% corresponds to "maximal dryness").	Assessed at Day 15
Change From Baseline in Total Corneal Fluorescein Staining (NEI Scale) at Day 15	The National Eye Institute (NEI) scale relies on a chart that divides the cornea into five sections (central, superior, temporal, nasal, and inferior) and assigns a value from 0 (absent) to 3 (severe) to each section, based on the amount, size, and confluence of the punctate keratitis, for a maximum total of 15 points (sum of scores for each section).	Assessed at Day 15
Change From Baseline in Burning/Stinging (Visual Analogue Scale [VAS] Severity of Burning/Stinging) at Day 57	Subjects will be asked about the severity of burning / stinging. Study staff will ask subjects to rate their ocular symptoms (both eyes simultaneously) due to ocular dryness by placing a vertical mark on a horizontal line to indicate the level of discomfort (0 corresponds to "no discomfort" and 100% corresponds to "maximal discomfort").	Assessed at Day 57
Change From Baseline in Central Corneal Fluorescein Staining (NEI Scale) at Day 57	The National Eye Institute (NEI) scale relies on a chart that divides the cornea into five sections (central, superior, temporal, nasal, and inferior) and assigns a value from 0 (absent) to 3 (severe) to each section, based on the amount, size, and confluence of the punctate keratitis, for a maximum of 3 points in the central section.	Assessed at Day 57

Collaborators and Investigators

• Sponsor: Bausch & Lomb Incorporated
• Investigators: Study Director: Daniel Donatello, Bausch & Lomb Incorporated

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2020
• Primary Completion (Actual): August 30, 2021
• Study Completion (Actual): August 30, 2021

Study Registration Dates

• First Submitted: September 23, 2020
• First Submitted That Met QC Criteria: September 23, 2020
• First Posted (Actual): September 28, 2020

Study Record Updates

• Last Update Posted (Actual): August 19, 2024
• Last Update Submitted That Met QC Criteria: July 22, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Eyelid Diseases; Eye Diseases; Dry Eye Syndromes; Keratoconjunctivitis Sicca; Meibomian Gland Dysfunction
• Other Study ID Numbers: 904

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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