Clinical trial NCT04567329: Effect of NOV03 on Signs and Symptoms of Dry Eye Disease Associated With Meibomian Gland Dysfunction (Mojave Study)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Dry Eye Disease
Lead sponsor: Bausch & Lomb Incorporated
Sponsor class: INDUSTRY
First posted: 2020-09-28
Enrollment: 620
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 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in Total Corneal Fluorescein Staining Score (NEI Scale) in the Study Eye at Day 57
timeFrame: Assessed at Day 57
measure: Change From Baseline in Dryness Score (Visual Analogue Scale [VAS] Severity of Dryness) at Day 57
timeFrame: Assessed at Day 57
Secondary outcomes:
measure: Change From Baseline in Dryness Score (Visual Analogue Scale [VAS] Severity of Dryness) at Day 15
timeFrame: Assessed at Day 15
measure: Change From Baseline in Total Corneal Fluorescein Staining (NEI Scale) at Day 15
timeFrame: Assessed at Day 15
measure: Change From Baseline in Burning/Stinging (Visual Analogue Scale [VAS] Severity of Burning/Stinging) at Day 57
timeFrame: Assessed at Day 57
measure: Change From Baseline in Central Corneal Fluorescein Staining (NEI Scale) at Day 57
timeFrame: Assessed at Day 57
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Bausch Site 206
state: Arizona
city: Garden Grove
country: United States
facility: Bausch Site 202
state: California
city: Hemet
country: United States
facility: Bausch Site 221
state: California
city: Inglewood
country: United States
facility: Bausch Site 214
state: California
city: Murrieta
country: United States
facility: Bausch Site 226
state: California
city: Santa Ana
country: United States
facility: Bausch Site 213
state: California
city: Westminster
country: United States
facility: Bausch site 236
state: California
city: Grand Junction
country: United States
facility: Bausch site 225
state: Colorado
city: Delray Beach
country: United States
facility: Bausch Site 211
state: Florida
city: Morrow
country: United States
facility: Bausch Site 204
state: Georgia
city: Chicago
country: United States
facility: Bausch Site 209
state: Illinois
city: Hoffman Estates
country: United States
facility: Bausch site 218
state: Illinois
city: Overland Park
country: United States
facility: Bausch Site 230
state: Kansas
city: Louisville
country: United States
facility: Bausch Site 207
state: Kentucky
city: Havre De Grace
country: United States
facility: Bausch Site 228
state: Maryland
city: Bloomington
country: United States
facility: Bausch Site 231
state: Minnesota
city: Saint Louis
country: United States
facility: Bausch Site 229
state: Missouri
city: Saint Louis
country: United States
facility: Bausch Site 224
state: Missouri
city: Washington
country: United States
facility: Bausch Site 217
state: Missouri
city: Rochester
country: United States
facility: Bausch Site 208
state: New York
city: Asheville
country: United States
facility: Bausch Site 210
state: North Carolina
city: High Point
country: United States
facility: Bausch site 233
state: North Carolina
city: Southern Pines
country: United States
facility: Bausch site 232
state: North Carolina
city: Cincinnati
country: United States
facility: Bausch Site 201
state: Ohio
city: Cleveland
country: United States
facility: Bausch Site 216
state: Ohio
city: Columbus
country: United States
facility: Bausch Site 223
state: Ohio
city: Nashville
country: United States
facility: Bausch Site 215
state: Tennessee
city: Austin
country: United States
facility: Bausch site 235
state: Texas
city: Cedar Park
country: United States
facility: Bausch Site 219
state: Texas
city: League City
country: United States
facility: Bausch Site 212
state: Texas
city: San Antonio
country: United States
facility: Bausch site 234
state: Texas
city: San Antonio
country: United States
facility: Bausch Site 222
state: Texas
city: San Antonio
country: United States
facility: Bausch Site 203
state: Texas
city: Norfolk
country: United States
facility: Bausch Site 220
state: Virginia
city: Seattle
country: United States
facility: Bausch Site 227
state: Washington
Study officials:
affiliation: Bausch & Lomb Incorporated
name: Daniel Donatello
role: STUDY_DIRECTOR
References: