A Study of the Drugs AGN-242428 and AGN-231868 in Participants With Dry Eye Disease

A Multicenter, Vehicle-controlled, Double-Masked, Randomized Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Exploratory Efficacy of AGN-242428 and AGN-231868 in Participants With Dry Eye Disease

This will be a 2 stage study in which Stage 1 will evaluate the safety of AGN-242428 and AGN-231868, how well they are tolerated and how they move through the body when administered. After the sponsor's determination of adequate safety and tolerability of the interventions in Stage 1, Stage 2 will begin. Stage 2 will also evaluate the safety and tolerability of AGN-242428 and AGN-231868, how effective they are in treating dry eye disease and assess the plasma and tear exposure of both ophthalmic solutions.

Study Overview

• Status: Completed
• Conditions: Dry Eye Syndrome; Dry Eye Disease
• Intervention / Treatment: Drug: AGN-242428; Drug: AGN-231868; Other: AGN-242428 Vehicle; Other: AGN-231868 Vehicle; Drug: Lifitegrast

• Study Type: Interventional
• Enrollment (Actual): 292
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Cornea and Cataract Consultants of Arizona /ID# 232769
  • California
    • Newport Beach, California, United States, 92663-3637
      • The Eye Research Foundation /ID# 232696
  • Colorado
    • Colorado Springs, Colorado, United States, 80907-7529
      • Vision Institute Central /ID# 239910
  • Kentucky
    • Louisville, Kentucky, United States, 40206
      • The Eye Care Institute /ID# 232683
  • Massachusetts
    • Andover, Massachusetts, United States, 01810
      • Andover Eye Associates /ID# 232689
  • North Carolina
    • Shelby, North Carolina, United States, 28150
      • Vita Eye Clinic /ID# 232721
  • Pennsylvania
    • Cranberry Township, Pennsylvania, United States, 16066
      • Scott and Christie and Associates /ID# 232746
  • Tennessee
    • Memphis, Tennessee, United States, 38119-5745
      • Total Eye Care, PA /ID# 232657
    • Smyrna, Tennessee, United States, 37167
      • Advancing Vision Research /ID# 232660
  • Utah
    • Clinton, Utah, United States, 84015-8562
      • Alpine Research Organization, Inc. /ID# 240508
  • Virginia
    • Lynchburg, Virginia, United States, 24502
      • Piedmont Eye Center /ID# 232698

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Stage 1 & Stage 2

• Male participants willing to minimize the risk of inducing pregnancy for the duration of the clinical study;
• Female participants willing to minimize the risk of inducing pregnancy for the duration of the clinical study;
• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol; Stage 1
• Both of the following signs of DED in at least 1 eye at Screening and Baseline visits (the same eye does not need to qualify at both visits);
• Total corneal fluorescein staining score ≥ 2 and ≤ 9 based on the NEI grading scale, with no score > 2 in any 1 region;
• Schirmer test with topical anesthesia score ≥ 1 and ≤ 10 mm/5 min; Stage 2
• ALL of the following in at least 1 eye at both the Screening and Baseline visits and the same eye must qualify at both Screening and Baseline visits;
• Corneal fluorescein staining score ≥ 2 in at least 1 eye region and a total corneal fluorescein staining score of ≥ 4 and ≤ 12 based on NEI grading scale
• Schirmer test with topical anesthesia score ≥ 2 and ≤ 10 mm/5 min;
• Mean TBUT of ≥ 2 and ≤ 10 seconds Stage 1
• Symptoms of DED at both the Screening and Baseline visits as defined by an OSDI total score of ≥ 13 with ≤ 3 responses of "not applicable (NA)"; Stage 2;
• Symptoms of DED at both the Screening and Baseline visits as defined by both:
• OSDI score of ≥ 23 with ≤ 3 responses of "not applicable (NA)" in at least 1 eye;
• Eye Dryness Score (assessed using the Visual Analog Scale (VAS) Symptom Items score ≥ 30

Exclusion Criteria:

• Current diagnosis of glaucoma or ocular hypertension; evidence of glaucoma or mean intraocular pressure > 21 mm Hg determined by Goldmann applanation tonometry, in either eye;
• Diagnosis of recurrent, ongoing, or active ocular infection including, but not limited to herpes simplex or zoster, vaccinia, varicella, tuberculosis of the eye, acanthamoeba, or fungal disease;
• Participation in a blood or plasma donation program within 60 or 30 days, respectively, prior to study intervention administration;
• Positive test results for anti-HIV type 1 and 2, hepatitis B surface antigen, or anti-hepatitis C virus at the Screening visit;
• Positive test results for benzoylecgonine (cocaine), methadone, barbiturates, amphetamines, benzodiazepines, alcohol, cannabinoids, opiates, or phencyclidine at the Screening or Baseline visits;
• Positive pregnancy test at Screening or Baseline visits;
• Currently breastfeeding or plans to breastfeed during the study;
• History or presence of any ocular disorder or condition (other than DED) in either eye that would, in the opinion of the investigator, likely interfere with the interpretation of the study results or participant safety.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

13

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stage 1: AGN-242428 Cohort 1A; Administration of AGN-242428 ophthalmic solution	Drug: AGN-242428; Ophthalmic solution administered as a topical eye drop
Experimental: Stage 1: AGN-242428 Cohort 1B; Administration of AGN-242428 ophthalmic solution	Drug: AGN-242428; Ophthalmic solution administered as a topical eye drop
Experimental: Stage 1: AGN-242428 Cohort 1C; Administration of AGN-242428 ophthalmic solution	Drug: AGN-242428; Ophthalmic solution administered as a topical eye drop
Experimental: Stage 1: AGN-231868 Cohort 1A; Administration of AGN-231868 ophthalmic solution	Drug: AGN-231868; Ophthalmic solution administered as a topical eye drop
Experimental: Stage 1: AGN-231868 Cohort 1B; Administration of AGN-231868 ophthalmic solution	Drug: AGN-231868; Ophthalmic solution administered as a topical eye drop
Experimental: Stage 1: AGN-231868 Cohort 1C; Administration of AGN-231868 ophthalmic solution	Drug: AGN-231868; Ophthalmic solution administered as a topical eye drop
Placebo Comparator: Stage 1: AGN-242428 Vehicle; Administration of matching placebo (vehicle) ophthalmic solution	Other: AGN-242428 Vehicle; Matching placebo (vehicle) ophthalmic solution administered as a topical eye drop
Placebo Comparator: Stage 1: AGN-231868 Vehicle; Administration of matching placebo (vehicle) ophthalmic solution	Other: AGN-231868 Vehicle; Matching placebo (vehicle) ophthalmic solution administered as a topical eye drop
Experimental: Stage 2: AGN-242428 Group 1; Administration of AGN-242428 ophthalmic solution	Drug: AGN-242428; Ophthalmic solution administered as a topical eye drop
Experimental: Stage 2: AGN-242428 Vehicle Group 2; Administration of matching placebo (vehicle) ophthalmic solution	Other: AGN-242428 Vehicle; Matching placebo (vehicle) ophthalmic solution administered as a topical eye drop
Experimental: Stage 2: AGN-231868 Group 3; Administration of AGN-231868 ophthalmic solution	Drug: AGN-231868; Ophthalmic solution administered as a topical eye drop
Experimental: Stage 2: AGN-231868 Vehicle Group 4; Administration of matching placebo (vehicle) ophthalmic solution	Other: AGN-231868 Vehicle; Matching placebo (vehicle) ophthalmic solution administered as a topical eye drop
Active Comparator: Lifitegrast; Administration of Lifitegrast ophthalmic solution	Drug: Lifitegrast; Ophthalmic solution administered as a topical eye drop

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stage 1: The incidence of adverse events (safety and tolerability)	The number of participants who experience one or more treatment emergent adverse events (TEAE)	15 Day Treatment Period
Stage 1: Area under the plasma concentration versus time curve from time 0 to time of the last measurable concentration (AUC0-tlast) after a single dose administration		Predose and up to 12 hours postdose
Stage 1: Area under the tear concentration versus time curve from time 0 to time of the last measurable concentration (AUC0-tlast) after a single dose administration		Predose and up to 12 hours postdose
Stage 1: Maximum plasma drug concentration (Cmax) after a single dose administration		Predose and up to 12 hours postdose
Stage 1: Maximum tear drug concentration (Cmax) after a single dose administration		Predose and up to 12 hours postdose
Stage 1: Time of maximum plasma drug concentration (Tmax) after a single dose administration		Predose and up to 12 hours postdose
Stage 1: Time of maximum tear drug concentration(Tmax) after a single dose administration		Predose and up to 12 hours postdose
Stage 1: Terminal elimination half-life (t1/2) after a single dose administration		Predose and up to 12 hours postdose
Stage 1: Area under the plasma concentration versus time curve from time 0 to the end of the dosing interval (AUC0-τ) following repeat dose administration		Predose and up to 12 hours postdose
Stage 1: Area under the tear concentration versus time curve from time 0 to the end of the dosing interval (AUC0-τ) following repeat dose administration		Predose and up to 12 hours postdose
Stage 1: Maximum plasma drug concentration (Cmax) following repeat dose administration		Predose and up to 12 hours postdose
Stage 1: Maximum tear drug concentration (Cmax) following repeat dose administration		Predose and up to 12 hours postdose
Stage 1: Time of maximum plasma drug concentration (Tmax) following repeat dose administration		Predose and up to 12 hours postdose
Stage 1: Time of maximum tear drug concentration (Tmax) following repeat dose administration		Predose and up to 12 hours postdose
Stage 1: Minimum plasma drug concentration at steady state (Cmin,ss) following repeat dose administration		Predose and up to 12 hours postdose
Stage 1: Minimum tear drug concentration at steady state (Cmin,ss) following repeat dose administration		Predose and up to 12 hours postdose
Stage 1: Terminal elimination half-life of the study drugs (t1/2) following repeat dose administration		Predose and up to 12 hours postdose
Stage 1: Accumulation index of drug concentration (AI) following repeat dose administration		Predose and up to 12 hours postdose
Stage 1: Drop Tolerability Questionnaire Score	Rate of the acute overall tolerability attributes of study interventions on an 8-question visual analog scale (VAS) Drop Tolerability Questionnaire. Visual scale ranges from 0=not at all comfortable to 100=very comfortable.	15 Day Treatment Period
Stage 1: Number of patients experiencing one or more adverse events (AEs) during the 15 day treatment period		15 Day Treatment Period
Stage 1: Potentially clinically significant (PCS) clinical laboratory values	The percentage of participants who have PCS postbaseline clinical laboratory values	15 Day Treatment Period
Stage 1: Vital sign values (blood pressure, pulse rate, weight, respiration rate, and temperature)	The percentage of participants who have PCS postbaseline vital sign values	15 Day Treatment Period
Stage 1: Electrocardiogram (ECG) heart rate	The percentage of participants who have PCS postbaseline ECG	15 Day Treatment Period
Stage 1: ECG PR interval	The percentage of participants who have PCS postbaseline ECG	15 Day Treatment Period
Stage 1: ECG QRS duration	The percentage of participants who have PCS postbaseline ECG	15 Day Treatment Period
Stage 1: ECG QT interval	The percentage of participants who have PCS postbaseline ECG	15 Day Treatment Period
Stage 1: ECG QTc	The percentage of participants who have PCS postbaseline ECG	15 Day Treatment Period
Stage 1: Change from baseline in intraocular pressure (IOP)		15 Day Treatment Period
Stage 1: Change from baseline in best-corrected visual acuity (BCVA)		15 Day Treatment Period
Stage 1: Change from baseline in slit-lamp biomicroscopy		15 Day Treatment Period
Stage 1: Change from baseline in dilated fundus examination		15 Day Treatment Period
Stage 2: The incidence of adverse events (safety and tolerability)	The number of participants who experience one or more treatment emergent adverse events (TEAE)	42 Day Treatment Period
Stage 2: Potentially clinically significant (PCS) clinical laboratory values	The percentage of participants who have PCS postbaseline clinical laboratory values	42 Day Treatment Period
Stage 2: Vital sign values (blood pressure, pulse rate, weight, respiration rate, and temperature)	The percentage of participants who have PCS postbaseline vital sign values	42 Day Treatment Period
Stage 2: Number of patients experiencing one or more adverse events (AEs) during the 42 day treatment period		42 Day Treatment Period
Stage 2: Electrocardiogram (ECG) heart rate	The percentage of participants who have PCS postbaseline ECG	42 Day Treatment Period
Stage 2: ECG PR interval	The percentage of participants who have PCS postbaseline ECG	42 Day Treatment Period
Stage 2: ECG QRS duration	The percentage of participants who have PCS postbaseline ECG	42 Day Treatment Period
Stage 2: ECG QT interval	The percentage of participants who have PCS postbaseline ECG	42 Day Treatment Period
Stage 2: ECG QTc	The percentage of participants who have PCS postbaseline ECG	42 Day Treatment Period
Stage 2: Change from baseline in intraocular pressure (IOP)		42 Day Treatment Period
Stage 2: Change from baseline in best-corrected visual acuity (BCVA)		42 Day Treatment Period
Stage 2: Change from baseline in slit-lamp biomicroscopy		42 Day Treatment Period
Stage 2: Change from baseline in dilated fundus examination		42 Day Treatment Period
Stage 2: Drop Tolerability Questionnaire Score	Rate of the acute overall tolerability attributes of study interventions on an 8-question visual analog scale (VAS) Drop Tolerability Questionnaire. Visual scale ranges from 0=not at all comfortable to 100=very comfortable.	42 Day Treatment Period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stage 2: Plasma exposure of AGN-242428 and AGN-231868 in participants with dry eye disease (DED) following twice daily dosing for up to 6 weeks	Plasma samples to determine concentrations will be collected at the nominal times	42 Day Treatment Period
Stage 2: Tear exposure of AGN-242428 and AGN-231868 in participants with dry eye disease (DED) following twice daily dosing for up to 6 weeks	Tear samples to determine concentrations will be collected at the nominal times	42 Day Treatment Period
Stage 2: Tear exposure of active comparator in participants with dry eye disease (DED) following twice daily dosing for up to 6 weeks	Tear samples to determine concentrations will be collected at the nominal times	42 Day Treatment Period

Collaborators and Investigators

• Sponsor: Allergan

Publications and helpful links

Helpful Links

• Additional information on study locations near you may be found at AllerganClinicalTrials.com.To be considered as a site for current and future Allergan Clinical Trials, please register using the Investigator Databank link.

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2020
• Primary Completion (Actual): March 18, 2022
• Study Completion (Actual): March 18, 2022

Study Registration Dates

• First Submitted: July 10, 2019
• First Submitted That Met QC Criteria: July 22, 2019
• First Posted (Actual): July 24, 2019

Study Record Updates

• Last Update Posted (Actual): March 20, 2023
• Last Update Submitted That Met QC Criteria: March 16, 2023
• Last Verified: March 1, 2023

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; Pharmaceutical Solutions; Ophthalmic Solutions; Lifitegrast
• Other Study ID Numbers: 2012-201-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• IPD Sharing Time Frame: For details on when studies are available for sharing, please refer to the link below.
• IPD Sharing Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Use Agreement (DUA). For more information on the process, or to submit a request, visit the following link.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

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.: Yes