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

NCT04030962 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 2012-201-005
• Study Type: interventional
• Target: 292
• Locations: 1 country
• Sites: 11

Brief Summary

This was a 2-stage study in which Stage 1 evaluated 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 began. Stage 2 also evaluated the safety and tolerability of AGN-242428 and AGN-231868, how effective they are in treating dry eye disease (DED), and assessed the plasma and tear exposure of both ophthalmic solutions.

Conditions

Dry Eye Disease; Dry Eye Syndrome

Outcome Measures

Primary Outcomes (30)

• Stage 1: Number of Participants With Adverse Events

  An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment.

  Day 1 to Day 15

• Stage 1: Area Under the Plasma Concentration Versus Time Curves After Single and Repeat Dose Administration

  Following single dose administration, the area under the plasma concentration versus time curves from time 0 to time of the last measurable concentration (AUC0-tlast; Visit 3) was calculated. Following repeat dose administration twice daily for 14 days, the area under the plasma concentration versus time curves from time 0 to the end of the dosing interval (AUC0-τ; Visit 5) was calculated. For Visit 3 and Visit 5, tlast was 12 hours post-dose.

  Day 2 and Day 15 (Predose and up to 12 hours postdose)

• Stage 1: Area Under the Tear Concentration Versus Time Curves After Single and Repeat Dose Administration

  Following single dose administration, the area under the tear concentration versus (vs) time curves from time 0 to time of the last measurable concentration (AUC0-tlast; Visit 3) was calculated. Following repeat dose administration twice daily for 14 days, the area under the tear concentration versus time curves from time 0 to the end of the dosing interval (AUC0-τ; Visit 5) was calculated. For Visit 3 and Visit 5, tlast was 12 hours post-dose.

  Day 2 and Day 15 (Predose and up to 12 hours postdose)

• Stage 1: Maximum Plasma Drug Concentration (Cmax) After Single and Repeat Dose Administration

  Following single dose administration, the plasma Cmax (Visit 3) was calculated. Following repeat dose administration twice daily for 14 days, the plasma Cmax (Visit 5) was calculated.

  Day 2 and Day 15 (Predose and up to 12 hours postdose)

• Stage 1: Maximum Tear Drug Concentration (Cmax) After Single and Repeat Dose Administration

  Following single dose administration, the tear Cmax (Visit 3) was calculated. Following repeat dose administration twice daily for 14 days, the tear Cmax (Visit 5) was calculated.

  Day 2 and Day 15 (Predose and up to 12 hours postdose)

• Stage 1: Time of Maximum Plasma Drug Concentration (Tmax) After Single and Repeat Dose Administration

  Following single dose administration, the plasma Tmax (Visit 3) was calculated. Following repeat dose administration twice daily for 14 days, the plasma Tmax (Visit 5) was calculated.

  Day 2 and Day 15 (Predose and up to 12 hours postdose)

• Stage 1: Time of Maximum Tear Drug Concentration (Tmax) After Single and Repeat Dose Administration

  Following single dose administration, the tear Tmax (Visit 3) was calculated. Following repeat dose administration twice daily for 14 days, the tear Tmax (Visit 5) was calculated.

  Day 2 and Day 15 (Predose and up to 12 hours postdose)

• Stage 1: Terminal Elimination Half-life of the Study Drugs (T1/2) in Plasma After Single Dose Administration

  Following single dose administration, the plasma T1/2 (Day 2; Visit 3) was calculated.

  Day 2 (Predose and up to 12 hours postdose).

• Stage 1: Terminal Elimination Half-life of the Study Drugs (T1/2) in Plasma After Repeat Dose Administration

  Following repeat dose administration twice daily for 14 days, plasma T1/2 (Day 15; Visit 5) was calculated.

  Day 15 (Predose and up to 12 hours postdose)

• Stage 1: Terminal Elimination Half-life of the Study Drugs (T1/2) in Tear After Single and Repeat Dose Administration

  Following single dose administration, the tear T1/2 (Visit 3) was calculated. Following repeat dose administration twice daily for 14 days, tear T1/2 (Visit 5) was calculated.

  Day 2 and Day 15 (Predose and up to 12 hours postdose)

• Stage 1: Minimum Tear Drug Concentration at Steady State (Cmin,ss) After Repeat Dose Administration

  Following repeat dose administration twice daily for 14 days, the tear Cmin,ss (Visit 5) was calculated.

  Day 15 (Predose and up to 12 hours postdose)

• Stage 1: Minimum Plasma Drug Concentration at Steady State (Cmin,ss) After Repeat Dose Administration

  Following repeat dose administration twice daily for 14 days, the plasma Cmin,ss (Visit 5) was calculated.

  Day 15 (Predose and up to 12 hours postdose)

• Stage 1: Mean Accumulation Index of Drug Concentration (AI) After Repeat Dose Administration

  Following repeat dose administration, the mean plasma and tear AI(area under curve \[AUC\]) was calculated. AI(AUC) is reported as the ratio of exposure (AUC) at steady state (Day 15) to the exposure after a single daily dose (Day 1). Values greater than one are indicative of drug accumulation with repeat dosing.

  Day 15 (up to 12 hours) / Day 1 (up to 12 hours)

• Stage 1: Mean Drop Tolerability Questionnaire Scores

  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. Higher mean scores indicate higher levels of comfort with the assigned intervention.

  Day 15

• Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values

  The percentage of participants with non-PCS baseline value and met PCS criterion at least once postbaseline for clinical laboratory values.

  Day 1 to Day 15

• Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature)

  The percentage of participants who met PCS criteria at least once postbaseline for vital sign values (sitting systolic and diastolic blood pressure, pulse rate, weight, respiration rate, and temperature)

  Day 1 to Day 15

• Stage 1: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values

  The percentage of participants with PCS postbaseline (but not at baseline) ECG values for QRS interval, PR interval, and QTc (Fridericia)

  Day 1 to Day 15

• Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP)

  At least 2 measurements were taken by qualified study site personnel using a Goldmann applanation tonometer affixed to a slit lamp with the participant seated.

  Day 1 to Day 15

• Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA)

  BCVA was quantified using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity protocol.

  Day 1 to Day 15

• Stage 1: Biomicroscopy: Percentage of Participants With Any Severity Increase From Baseline

  The number of participants with any ophthalmoscopy findings of any severity increase from baseline at one or more visit.

  Day 1 to Day 15

• Stage 1: Percentage of Participants With Any Clinically Significant Postbaseline Findings During Dilated Fundus Examination

  The fundus (posterior pole; periphery, when dilated) was evaluated for pathology. Ophthalmoscopy with clinically significant findings (per investigator assessment) postbaseline are reported.

  Day 1 to Day 15

• Stage 2: Number of Participants With Adverse Events

  An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment.

  Day 1 to Day 42

• Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values

  The percentage of participants who have PCS postbaseline clinical laboratory values at Day 42 (Visit 6).

  Day 42

• Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature)

  The percentage of participants who met PCS criteria at least once postbaseline for vital sign values at Day 42 (Visit 6) (sitting systolic and diastolic blood pressure, pulse rate, weight, respiration rate, and temperature). The numerator for the incidence is the number of participants with non-PCS baseline and at least one post-baseline value meeting the specific criterion at the visit. The denominator is the number of participants with non-PCS baseline and at least one post-baseline assessment at the visit. If a participant did not have a baseline value, but met the criterion post-baseline, then the participant is counted in the numerator.

  Day 42

• Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values

  The percentage of participants who have PCS ECG at Visit 6 (but not baseline) pre and post-controlled adverse environment (CAE). The numerator for the incidence is the number of participants with non-PCS baseline and at least one post-baseline value meeting the specific criterion at the visit. The denominator is the number of participants with non-PCS baseline and at least one post-baseline assessment at the visit. If a participant did not have a baseline value, but met the criterion post-baseline, then the participant is counted in the numerator.

  Day 42

• Stage 2: Mean Change From Baseline in Intraocular Pressure (IOP)

  At least 2 IOP measurements were taken by qualified study site personnel using a Goldmann applanation tonometer affixed to a slit lamp with the participant seated. Average intraocular pressure = mean of the 2 (or 3) measures in the study eye and non-study eye. Total fluorescein scores and Schirmer values were used to determine the study eye, and if both eyes qualified, the right eye was designated by default.

  Day 1, Day 42

• Stage 2: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA)

  BCVA was quantified using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity protocol in the study eye and the non-study eye. Total fluorescein scores and Schirmer values were used to determine the study eye, and if both eyes qualified, the right eye was designated by default.

  Day 1, Day 42

• Stage 2: Slit-lamp Biomicroscopy: Percentage of Participants With Any Clinically Significant Finding Postbaseline

  Percentage of participants with a clinically significant finding postbaseline, post-CAE. A clinically significant finding is defined as more than one severity grade increase (worsening) from baseline or positive status change from absence at baseline to presence at postbaseline (not associated with a severity grade) in one or both eyes.

  Day 1 to Day 42

• Stage 2: Percentage of Participants With Any Clinically Significant Postbaseline Findings During Dilated Fundus Examination

  The fundus (posterior pole; periphery, when dilated) was evaluated for pathology. Ophthalmoscopy with clinically significant findings (per investigator assessment) postbaseline are reported.

  Day 1 to Day 42

• Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment)

  Acute overall tolerability attributes of study interventions on an 8-question visual analog scale (VAS) Drop Tolerability Questionnaire. Participants completed questionnaires after exposure to a controlled adverse environment (CAE) for approximately 90 minutes. Visual scale ranges from 0 = not at all comfortable to 100 = very comfortable. Higher mean scores indicate higher levels of comfort with the assigned intervention.

  Day 42 (Post-CAE)

Secondary Outcomes (2)

• Stage 2: Trough Plasma Concentration (Ctrough) and Plasma Concentration at 0.5 Hours Postdose (C0.5h)

  Day 42

• Stage 2: Trough Tear Concentration (Ctrough) and Tear Concentration at 0.5 Hours Postdose (C0.5h)

  Day 42

Study Arms (13)

Stage 1 Cohort 1A: AGN-242428 Low Dose

EXPERIMENTAL

Administration of AGN-242428 ophthalmic solution

Drug: AGN-242428

Stage 1 Cohort 1A: AGN-242428 Vehicle

PLACEBO COMPARATOR

Administration of matching placebo (vehicle) ophthalmic solution

Other: AGN-242428 Vehicle

Stage 1 Cohort 1A: AGN-231868 Lose Dose

EXPERIMENTAL

Administration of AGN-231868 ophthalmic solution

Drug: AGN-231868

Stage 1 Cohort 1A: AGN-231868 Vehicle

PLACEBO COMPARATOR

Administration of matching placebo (vehicle) ophthalmic solution

Other: AGN-231868 Vehicle

Stage 1 Cohort 1B: AGN-242428 High Dose

EXPERIMENTAL

Administration of AGN-242428 ophthalmic solution

Drug: AGN-242428

Stage 1 Cohort 1B: AGN-242428 Vehicle

PLACEBO COMPARATOR

Administration of matching placebo (vehicle) ophthalmic solution

Other: AGN-242428 Vehicle

Stage 1 Cohort 1B: AGN-231868 High Dose

EXPERIMENTAL

Administration of AGN-231868 ophthalmic solution

Drug: AGN-231868

Stage 1 Cohort 1B: AGN-231868 Vehicle

PLACEBO COMPARATOR

Administration of matching placebo (vehicle) ophthalmic solution

Other: AGN-231868 Vehicle

Stage 2 Cohort 2: AGN-242428 High Dose

EXPERIMENTAL

Administration of AGN-242428 ophthalmic solution

Drug: AGN-242428

Stage 2 Cohort 2: AGN-242428 Vehicle

PLACEBO COMPARATOR

Administration of matching placebo (vehicle) ophthalmic solution

Other: AGN-242428 Vehicle

Stage 2 Cohort 2: AGN-231868 High Dose

EXPERIMENTAL

Administration of AGN-231868 ophthalmic solution

Drug: AGN-231868

Stage 2 Cohort 2: AGN-231868 Vehicle

PLACEBO COMPARATOR

Administration of matching placebo (vehicle) ophthalmic solution

Other: AGN-231868 Vehicle

Stage 2 Cohort 2: Lifitegrast Ophthalmic Solution

ACTIVE COMPARATOR

Administration of Lifitegrast ophthalmic solution

Drug: Lifitegrast 5% Ophthalmic Solution

Interventions

AGN-242428 DRUG

Ophthalmic solution administered as a topical eye drop

Stage 1 Cohort 1A: AGN-242428 Low Dose; Stage 1 Cohort 1B: AGN-242428 High Dose; Stage 2 Cohort 2: AGN-242428 High Dose

AGN-231868 DRUG

Ophthalmic solution administered as a topical eye drop

Stage 1 Cohort 1A: AGN-231868 Lose Dose; Stage 1 Cohort 1B: AGN-231868 High Dose; Stage 2 Cohort 2: AGN-231868 High Dose

AGN-242428 Vehicle OTHER

Matching placebo (vehicle) ophthalmic solution administered as a topical eye drop

Stage 1 Cohort 1A: AGN-242428 Vehicle; Stage 1 Cohort 1B: AGN-242428 Vehicle; Stage 2 Cohort 2: AGN-242428 Vehicle

AGN-231868 Vehicle OTHER

Matching placebo (vehicle) ophthalmic solution administered as a topical eye drop

Stage 1 Cohort 1A: AGN-231868 Vehicle; Stage 1 Cohort 1B: AGN-231868 Vehicle; Stage 2 Cohort 2: AGN-231868 Vehicle

Lifitegrast 5% Ophthalmic Solution DRUG

Ophthalmic solution administered as a topical eye drop

Also known as: Xiidra

Stage 2 Cohort 2: Lifitegrast Ophthalmic Solution

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)."

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie: lead

Study Sites (11)

Cornea and Cataract Consultants of Arizona /ID# 232769

Phoenix, Arizona, 85032, United States

Location

The Eye Research Foundation /ID# 232696

Newport Beach, California, 92663-3637, United States

Location

Vision Institute Central /ID# 239910

Colorado Springs, Colorado, 80907-7529, United States

Location

The Eye Care Institute /ID# 232683

Louisville, Kentucky, 40206, United States

Location

Andover Eye Associates /ID# 232689

Andover, Massachusetts, 01810, United States

Location

Vita Eye Clinic /ID# 232721

Shelby, North Carolina, 28150, United States

Location

Scott and Christie and Associates /ID# 232746

Cranberry Township, Pennsylvania, 16066, United States

Location

Total Eye Care, PA /ID# 232657

Memphis, Tennessee, 38119-5745, United States

Location

Advancing Vision Research /ID# 232660

Smyrna, Tennessee, 37167, United States

Location

Duplicate_Alpine Research Organization, Inc. /ID# 240508

Clinton, Utah, 84015-8562, United States

Location

Piedmont Eye Center /ID# 232698

Lynchburg, Virginia, 24502, United States

Location

MeSH Terms

Conditions

Dry Eye Syndromes

Interventions

lifitegrast; Ophthalmic Solutions

Condition Hierarchy (Ancestors)

Lacrimal Apparatus Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Pharmaceutical Solutions; Solutions; Pharmaceutical Preparations; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Specialty Uses of Chemicals

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie

abbvieclinicaltrials@abbvie.com

800-633-9110

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2019
• First Posted: July 24, 2019
• Study Start: March 4, 2020
• Primary Completion: March 18, 2022
• Study Completion: March 18, 2022
• Last Updated: May 20, 2025
• Results First Posted: May 20, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: For details on when studies are available for sharing, please refer to the link below.
• 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.

Locations

US (11)