A Phase 3, Multi-Center Study Evaluating PL9643 in Patients with Dry Eye (MELODY-1)

A Phase 3, Multi-center, Randomized, Double-Masked and Vehicle-Controlled Study Evaluating the Efficacy and Safety of the Melanocortin, PL9643 Ophthalmic Solution, Compared to Vehicle in Subjects with Dry Eye

This is a multi-center, double-masked, randomized, vehicle-controlled study testing PL9643, an ophthalmic solution to determine if safe and efficacious for dry eye patients.

After a 2-week run-in period, patients will be randomized equally to the PL9643 ophthalmic solution or vehicle ophthalmic solution administered bilaterally three times a day for 12 weeks.

A Data Monitoring Committee was engaged to review interim data.

Study Overview

• Status: Completed
• Conditions: Dry Eye; Dry Eye Syndromes
• Intervention / Treatment: Drug: PL9643 Ophthalmic Solution; Drug: Vehicle Ophthalmic Solution

Detailed Description

This is a multi-center, double-masked, randomized, vehicle-controlled study testing PL9643, an ophthalmic solution, to determine the safety and efficacy against a vehicle in dry eye patients.

During a 2-week/14-day study run-in period (for the purpose of subject selection) prior to randomization, all subjects will receive Vehicle Ophthalmic Solution (vehicle) bilaterally three times a day. Randomization will then occur in a 1:1 ratio where patients will be assigned to receive PL9643 ophthalmic solution given bilaterally three times a day or vehicle ophthalmic solution administered bilaterally three times a day. The treatment period is 12 weeks.

• Study Type: Interventional
• Enrollment (Actual): 575
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States, 91204
      • Global Research Management
    • Newport Beach, California, United States, 92663
      • Eye Research Foundation
    • Torrance, California, United States, 90505
      • East West Eye Institute
  • Indiana
    • Columbus, Indiana, United States, 47203
      • Pankratz Eye Institute
    • Indianapolis, Indiana, United States, 46240
      • Michael Washburn Center for Ophthalmic Research, LLC
  • Kentucky
    • Lexington, Kentucky, United States, 40517
      • Kentucky Eye Institute
    • Louisville, Kentucky, United States, 40206
      • Butchertown Clinical Trials
  • Massachusetts
    • Andover, Massachusetts, United States, 01810
      • Andover Eye Associates
  • Nevada
    • Las Vegas, Nevada, United States, 89052
      • Center for Sight
  • North Carolina
    • Mint Hill, North Carolina, United States, 28227
      • Mint Hill
    • Shelby, North Carolina, United States, 28150
      • CORE, Inc
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • Bergstrom Eye research, LLC
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16507
      • Erie Retina Research, LLC
  • Tennessee
    • Goodlettsville, Tennessee, United States, 37072
      • Advancing Vision Research
    • Memphis, Tennessee, United States, 38119
      • Total Eye Care, PA
    • Smyrna, Tennessee, United States, 37167
      • Advancing Vision Research
  • Texas
    • Austin, Texas, United States, 78750
      • Austin Clinical Research
    • Dallas, Texas, United States, 75243
      • Axis Clinical

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Be at least 18 years of age;
2. Provide written informed consent;
3. Be willing and able to comply with all study procedures;
4. Have a patient-reported history of dry eye for at least 5 years prior to Visit 1;
5. Have a history of use or desire to use eye drops for dry eye symptoms within 6 months of Visit 1;
6. Have a best corrected visual acuity (BCVA) of 0.7 logarithm of the minimum angle of resolution (logMAR) or better (Snellen equivalent score of 20/100 or better) in each eye at Visit 1;
7. Have an inferior fluorescein corneal staining score > 1 at both Visits 1 and 2 Pre-CAE®;
8. Have an Eye Discomfort from the Visual Analog Scale (VAS) ≥25 at both Visits 1 and 2 Pre-CAE®;
9. Report a score of ≥ 2 according to the Ora Calibra® Ocular Discomfort & 4-Symptom Questionnaire in at least one of the dry eye symptoms at Visits 1 and 2 Pre-CAE®;
10. Have a Schirmer's Test score of ≤ 10 mm and ≥ 1 mm at Visits 1 and 2;
11. Have a corneal fluorescein staining score of ≥ 2 in any corneal region (inferior, central or superior) according to the Ora Calibra® Corneal and Conjunctival Staining Scale for Grading of Fluorescein Staining in at least one eye at Visits 1 and 2 Pre-CAE®;
12. Have a conjunctival redness score ≥ 1 according to the Ora Calibra® Conjunctival Redness for Dry Eye Scale in at least one eye at Visits 1 and 2 Pre-CAE®;

13. Demonstrate in the same eye(s) a response to the CAE®at Visits 1 and 2 as defined by:

    1. Having at least a ≥1 point increase in fluorescein staining in the inferior region in at least one eye following CAE® exposure;
    2. Reporting an Ocular Discomfort score ≥3 at 2 or more consecutive time points in at least one eye during CAE® exposure (if a subject has an Ocular Discomfort rating of 3 at time = 0 for an eye, s/he must report an Ocular Discomfort rating of 4 for two consecutive measurements for that eye). Note: a subject cannot have an Ocular Discomfort score of 4 at time = 0);
14. Have at least one eye, the same eye, satisfy all criteria for 7, 8, 9, 10, 11, 12 and 13 above;
15. A negative urine pregnancy test if female of childbearing potential (those who are not surgically sterilized [bilateral tubal ligation, hysterectomy or bilateral oophorectomy] or post-menopausal [12 months after last menses]) and must use adequate birth control through the study period. For non-sexually active females, abstinence may be regarded as an adequate method of birth control

Exclusion Criteria:

1. Have any clinically significant slit-lamp findings at Visit 1 that may include active blepharitis, meibomian gland dysfunction, lid margin inflammation, or active ocular allergies that require therapeutic treatment, and/or in the opinion of the Investigator may interfere with study parameters;
2. Be diagnosed with an ongoing ocular infection (bacterial, viral, or fungal), or active ocular inflammation at Visit 1 or Visit 2;
3. Have worn contact lenses within 7 days of Visit 1 or anticipate using contact lenses during the study;
4. Have previously had laser-assisted in situ keratomileusis (LASIK) surgery within the last 12 months;
5. Have used Restasis®, Xiidra®, Cequa®, or Eysuvis® within 60 days of Visit 1;
6. Have had any ocular and/or lid surgeries in the past 6 months or have any planned ocular and/or lid surgeries over the study period;
7. Have had any laser procedures (e.g. YAG capsulotomy) in the past 3 months;
8. Be using or anticipate using temporary punctal plugs during the study that have not been stable within 30 days of Visit 1;

9. Be currently taking any topical ophthalmic prescription (including medications for glaucoma) or over-the-counter solutions, artificial tears, gels or scrubs, and cannot discontinue these medications for the duration of the trial (excluding medications allowed for the conduct of the study); the respective wash-out periods are required for thefollowing medications:

   1. Ocular, oral or nasal antihistamines: 72 hours prior to Visit 1 and during the study.
   2. Oral aspirin or aspirin-containing products allowed if dose has been stable over past 30 days prior to Visit 1 and no change in dose is anticipated during the study period
   3. Corticosteroids or mast cell stabilizers (including ocular): 14 days prior to Visit 1
   4. Any medication (oral or topical) known to cause ocular drying that has not been administered as a stable dose for at least 30 days prior to Visit 1 and during the study
   5. All other topical ophthalmic preparations (including artificial tear substitutes) other than the study drops: 72 hours prior to Visit 1
10. Have an uncontrolled systemic disease;
11. Be a woman who is pregnant, nursing, or planning a pregnancy;
12. Be unwilling to submit a urine pregnancy test at Visit 1 and Visit 6 (or early termination visit) if of childbearing potential. Non-childbearing potential is defined as a woman who is permanently sterilized (e.g., bilateral tubal ligation, hysterectomy or bilateral oophorectomy), or is post-menopausal (without menses for 12 consecutive months);
13. Be a woman of childbearing potential who is not using an acceptable means of birth control; acceptable methods of contraception include: 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 may be regarded as an adequate method of birth control; however, if the subject becomes sexually active during the study, she must agree to use adequate birth control as defined above for the remainder of the study;
14. Have a known allergy and/or sensitivity to the test article or its components;
15. Have a condition or be in a situation which the Investigator feels may put the subject at significant risk, may confound the study results, or may interfere significantly with the subject's participation in the study;
16. Have used an investigational drug or device within 30 days of Visit 1 unless the Investigator or Sponsor deems a washout period of up to 60 days is required;
17. Participated in a previous clinical study involving PL9643;
18. Be unable or unwilling to follow instructions, including participation in all study assessments and visits.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PL9643 Ophthalmic Solution; PL9643 ophthalmic solution bilaterally three times a day.	Drug: PL9643 Ophthalmic Solution; Ophthalmic Solution; Other Names: Active study medication
Active Comparator: Vehicle Ophthalmic Solution; Vehicle ophthalmic solution bilaterally three times a day.	Drug: Vehicle Ophthalmic Solution; Ophthalmic Solution; Other Names: Control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Conjunctival Sum Lissamine Green Staining	Measured by the Ora Calibra® Scale. Change from Baseline to week 12.	Visit 6 (Day 85), Change from Pre-CAE to Post-CAE
Ocular Pain	As Measured by Visual Analog Scale (VAS). PL9643 versus Vehicle, in hyper-responder sub-population. Hyper-responder sub-population is defined as those patients achieving a VAS score of 4 or greater within the first 30 minutes of being challenged in the CAE® (clinical symptom) at Visit 2.	Change from Pre-CAE to Post-CAE at Visit 6 (Day 85)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nasal Lissamine Green Staining in Study Eye	As measured by Ora Calibra Scale at Visit 6 (Day 85) in Study Eye	Change from Baseline to Visit 6 (Day 85), Pre-CAE
Tear Film Break-Up Time (TFBUT) in Study Eye	Change from Baseline Post-CAE® to Week 12 Post-CAE®	Change from Baseline to Visit 6 (Day 85), Post-CAE
Total Sum Lissamine Green Staining in Study Eye	As measured by Ora Calibra Scale at Visit 6 (Day 85) in Study Eye	Change from Baseline Pre-CAE® to Week 12 Pre-CAE
Ocular Pain for ITT	As Measured by Visual Analog Scale at Visit 6 (Day 85), PL9643 versus Vehicle, In ITT population	Visit 6 (Day 85), Change from Pre-CAE to Post-CAE
Inferior Fluorescein Staining in Study Eye	As Measured by Ora Calibra Scale at Visit 6 (Day 85) in Study Eye	Change from Baseline to Visit 6 (Day 85), Post-CAE
Inferior Corneal Fluorescein Staining in Study Eye	As measured by Ora Calibra Scale at Visit 6 (Day 85) in Study Eye	Change from Baseline to Visit 6 (Day 85), Pre-CAE
Foreign Body Sensation for Hyper-Responders	As Measured by Visual Analog Scale at Visit 6 (Day 85) for Hyper-Responders	Visit 6 (Day 85), Change from Pre-CAE to Post-CAE
Eye Dryness for Hyper-Responders versus Vehicle in hyper-responder sub-population	As Measured by Visual Analog Scale at Visit 6 (Day 85) for Hyper-Responders	Change from Baseline to Visit 6 (Day 85), Post-CAE
Unanesthetized Schirmer Test Result (mm) in Study Eye	Measured at Visit 6 (Day 85) in Study Eye	Change from Baseline to Visit 6 (Day 85), Pre-CAE
Eye Discomfort for Hyper-responders versus Vehicle in hyper-responder sub-population	As Measured by Visual Analog Scale at Visit 6 (Day 85) for Hyper-responders	Change from Baseline to Visit 6 (Day 85), Post-CAE

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain for Hyper-Responders	As Measured by Visual Analog Scale at Visit 3 (Day 15) for Hyper-Responders	Change from Baseline to Visit 3 (Day 15), Post-CAE
Pain for ITT	As Measured by Visual Analog Scale at Visit 3 (Day 15) PL9643 versus Vehicle, In ITT population	Visit 3 (Day 15), Change from Pre-CAE to Post-CAE
Eye Discomfort for Hyper-responders	As Measured by Visual Analog Scale, Pre-CAE at Visit 3 (Day 15) for Hyper-responders	Visit 3 (Day 15), Change from Pre-CAE to Post-CAE

Collaborators and Investigators

• Sponsor: Palatin Technologies, Inc
• Investigators: Study Director: Brian Dodge, Palatin

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2021
• Primary Completion (Actual): September 1, 2023
• Study Completion (Actual): November 21, 2023

Study Registration Dates

• First Submitted: January 8, 2022
• First Submitted That Met QC Criteria: January 8, 2022
• First Posted (Actual): January 21, 2022

Study Record Updates

• Last Update Posted (Actual): October 17, 2024
• Last Update Submitted That Met QC Criteria: October 15, 2024
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Eye diseases; Dry eye; Pharmaceutical Solutions; Ophthalmology; Ophthalmic Solutions; Corneal diseases; Conjunctival diseases
• Additional Relevant MeSH Terms: Eye Diseases; Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Dry Eye Syndromes; Keratoconjunctivitis Sicca; Ophthalmic Solutions; Pharmaceutical Solutions
• Other Study ID Numbers: PL9643-301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No