Dry Eye DiseasePhase 1/2NCT04030962
A Study of the Drugs AGN-242428 and AGN-231868 in Participants With Dry Eye Disease
A Phase 1/2 study testing AGN-242428, AGN-231868 and Lifitegrast 5% Ophthalmic Solution in people with Dry Eye Disease and Dry Eye Syndrome, run by AbbVie at 11 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Dry Eye Disease, Dry Eye Syndrome
- What is being tested?
- AGN-242428, AGN-231868 and Lifitegrast 5% Ophthalmic Solution
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 292 participants
- Where
- 11 sitesUnited States
- Study dates
- 4 Mar 2020to 18 Mar 2022
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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):
Show all 19Show fewer
- 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).
Who cannot join
- 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.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
Andover Eye Associates /ID# 232689
Andover, Massachusetts, 01810
Duplicate_Alpine Research Organization, Inc. /ID# 240508
Clinton, Utah, 84015-8562
Vision Institute Central /ID# 239910
Colorado Springs, Colorado, 80907-7529
Scott and Christie and Associates /ID# 232746
Cranberry Township, Pennsylvania, 16066
The Eye Care Institute /ID# 232683
Louisville, Kentucky, 40206
Piedmont Eye Center /ID# 232698
Lynchburg, Virginia, 24502
Total Eye Care, PA /ID# 232657
Memphis, Tennessee, 38119-5745
The Eye Research Foundation /ID# 232696
Newport Beach, California, 92663-3637
Cornea and Cataract Consultants of Arizona /ID# 232769
Phoenix, Arizona, 85032
Vita Eye Clinic /ID# 232721
Shelby, North Carolina, 28150
Advancing Vision Research /ID# 232660
Smyrna, Tennessee, 37167
About this study
Official title: 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 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.
Read the detailed description
Participants with DED in Cohort 1A were randomized 3:3:1:1 to receive AGN-242428 (Low Dose), AGN-231868 (Low Dose), or their respective vehicles (4 treatment groups total) to the left eye on Day 1 (Visit 2). If there were no significant study drug-related safety findings, starting on Day 2, participants administered the same randomized study drug twice daily to both eyes through Day 14, followed by a single dose administration to both eyes on Day 15 (Visit 5).
Upon completion of Cohort 1A, an independent data monitoring committee reviewed the data before proceeding to the next cohort. Cohort 1B participants were randomized 3:3:1:1 to receive AGN-242428 (High Dose), AGN-231868 (High Dose), or their respective vehicles (4 treatment groups total) and followed the same dosing regimen used in Cohort 1A.
All subjects enrolled in Stage 2 had DED. In addition, subjects were selected based on their response to a controlled adverse environment (CAE). Only subjects with DED who responded to the CAE exposure with an increase in the signs and symptoms of DED were enrolled in Stage 2.
During Stage 2, participants were randomized in a 1:1:1:1:1 ratio (within each site), to receive AGN-242428 (High Dose), AGN-242428 vehicle, AGN-231868 (High Dose), AGN-231868 vehicle, or Lifitegrast Ophthalmic Solution (Xiidra). Participants administered the assigned study drug in each eye twice daily for 41 days, followed by a single administration during the morning on Day 42.
- Conditions
- Dry Eye Disease, Dry Eye Syndrome
- Being tested
- AGN-242428, AGN-231868, AGN-242428 Vehicle, AGN-231868 Vehicle, Lifitegrast 5% Ophthalmic Solution
- Medical subject headings
- Dry Eye Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AGN-242428Drug
Ophthalmic solution administered as a topical eye drop
AGN-231868Drug
Ophthalmic solution administered as a topical eye drop
AGN-242428 VehicleOther
Matching placebo (vehicle) ophthalmic solution administered as a topical eye drop
AGN-231868 VehicleOther
Matching placebo (vehicle) ophthalmic solution administered as a topical eye drop
Lifitegrast 5% Ophthalmic SolutionDrug
Also called Xiidra
Ophthalmic solution administered as a topical eye drop
| Study group | Role | What they receive |
|---|---|---|
| Stage 1 Cohort 1A: AGN-242428 Low Dose | Experimental | Administration of AGN-242428 ophthalmic solution Receives: Drug: AGN-242428 |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Placebo comparator | Administration of matching placebo (vehicle) ophthalmic solution Receives: Other: AGN-242428 Vehicle |
| Stage 1 Cohort 1A: AGN-231868 Lose Dose | Experimental | Administration of AGN-231868 ophthalmic solution Receives: Drug: AGN-231868 |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Placebo comparator | Administration of matching placebo (vehicle) ophthalmic solution Receives: Other: AGN-231868 Vehicle |
| Stage 1 Cohort 1B: AGN-242428 High Dose | Experimental | Administration of AGN-242428 ophthalmic solution Receives: Drug: AGN-242428 |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Placebo comparator | Administration of matching placebo (vehicle) ophthalmic solution Receives: Other: AGN-242428 Vehicle |
| Stage 1 Cohort 1B: AGN-231868 High Dose | Experimental | Administration of AGN-231868 ophthalmic solution Receives: Drug: AGN-231868 |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Placebo comparator | Administration of matching placebo (vehicle) ophthalmic solution Receives: Other: AGN-231868 Vehicle |
| Stage 2 Cohort 2: AGN-242428 High Dose | Experimental | Administration of AGN-242428 ophthalmic solution Receives: Drug: AGN-242428 |
| Stage 2 Cohort 2: AGN-242428 Vehicle | Placebo comparator | Administration of matching placebo (vehicle) ophthalmic solution Receives: Other: AGN-242428 Vehicle |
| Stage 2 Cohort 2: AGN-231868 High Dose | Experimental | Administration of AGN-231868 ophthalmic solution Receives: Drug: AGN-231868 |
| Stage 2 Cohort 2: AGN-231868 Vehicle | Placebo comparator | Administration of matching placebo (vehicle) ophthalmic solution Receives: Other: AGN-231868 Vehicle |
| Stage 2 Cohort 2: Lifitegrast Ophthalmic Solution | Active comparator | Administration of Lifitegrast ophthalmic solution Receives: Drug: Lifitegrast 5% Ophthalmic Solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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)
Measured: 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)
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Day 42 (Post-CAE)
Secondary outcomes (2)
Stage 2: Trough Plasma Concentration (Ctrough) and Plasma Concentration at 0.5 Hours Postdose (C0.5h)
Trough plasma concentration (Ctrough) and plasma concentration at 0.5 hours postdose (C0.5h), following twice daily dosing for up to 6 weeks
Measured: Day 42
Stage 2: Trough Tear Concentration (Ctrough) and Tear Concentration at 0.5 Hours Postdose (C0.5h)
Trough tear concentration (Ctrough) and tear concentration at 0.5 hours postdose (C0.5h), following twice daily dosing for up to 6 weeks
Measured: Day 42
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2019
- Study start4 Mar 2020
- Primary completion18 Mar 2022
- Study completion18 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Dry Eye DiseaseStudies of the same condition, open and under way.
- More trials run by AbbVieThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 292 participants (actual)
Sponsor and investigators
- Lead sponsor
- AbbVie
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- ABBVIE INC., Study director, AbbVie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04030962
- Sponsor's protocol ID
- 2012-201-005
- Status last verified
- May 2025
- First submitted
- 10 Jul 2019
- Last updated
- 20 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Tunon-Robinson I, Zheng S, Zhao C, Nguyen AK, Gomez-Freeman L. Selecting Vehicle Comparators in Dry Eye Disease Clinical Trials: Implications for Efficacy and Safety Assessment and Regulatory Outcomes. Ophthalmol Ther. 2026 Sep 7. doi: 10.1007/s40123-026-01490-2. Online ahead of print.
PubMed 42704415
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04030962
- Acronym / sponsor ID
- 2012-201-005
- Conditions
- Dry Eye Disease, Dry Eye Syndrome
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 292 participants (actual)
- Lead sponsor
- AbbVieIndustry (pharma, biotech, devices)
- Study start
- 4 Mar 2020 (actual)
- Primary completion
- 18 Mar 2022 (actual)
- Study completion
- 18 Mar 2022 (actual)
- First posted
- 24 Jul 2019 (actual)
- Results
- Posted 20 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Participants with DED in Cohort 1A were randomized 3:3:1:1 to receive AGN-242428 (Low Dose), AGN-231868 (Low Dose), or their respective vehicles (4 treatment groups total) to the left eye on Day 1 (Visit 2). If there were no significant study drug-related safety findings, starting on Day 2, participants administered the same randomized study drug twice daily to both eyes through Day 14, followed by a single dose administration to both eyes on Day 15 (Visit 5).
Upon completion of Cohort 1A, an independent data monitoring committee reviewed the data before proceeding to the next cohort. Cohort 1B participants were randomized 3:3:1:1 to receive AGN-242428 (High Dose), AGN-231868 (High Dose), or their respective vehicles (4 treatment groups total) and followed the same dosing regimen used in Cohort 1A.
All subjects enrolled in Stage 2 had DED. In addition, subjects were selected based on their response to a controlled adverse environment (CAE). Only subjects with DED who responded to the CAE exposure with an increase in the signs and symptoms of DED were enrolled in Stage 2.
During Stage 2, participants were randomized in a 1:1:1:1:1 ratio (within each site), to receive AGN-242428 (High Dose), AGN-242428 vehicle, AGN-231868 (High Dose), AGN-231868 vehicle, or Lifitegrast Ophthalmic Solution (Xiidra). Participants administered the assigned study drug in each eye twice daily for 41 days, followed by a single administration during the morning on Day 42.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 13
| Arm | Type | Receives |
|---|---|---|
| Stage 1 Cohort 1A: AGN-242428 Low Dose | Experimental | Drug: AGN-242428Administration of AGN-242428 ophthalmic solution |
| Stage 1 Cohort 1A: AGN-242428 Vehicle | Placebo comparator | Other: AGN-242428 VehicleAdministration of matching placebo (vehicle) ophthalmic solution |
| Stage 1 Cohort 1A: AGN-231868 Lose Dose | Experimental | Drug: AGN-231868Administration of AGN-231868 ophthalmic solution |
| Stage 1 Cohort 1A: AGN-231868 Vehicle | Placebo comparator | Other: AGN-231868 VehicleAdministration of matching placebo (vehicle) ophthalmic solution |
| Stage 1 Cohort 1B: AGN-242428 High Dose | Experimental | Drug: AGN-242428Administration of AGN-242428 ophthalmic solution |
| Stage 1 Cohort 1B: AGN-242428 Vehicle | Placebo comparator | Other: AGN-242428 VehicleAdministration of matching placebo (vehicle) ophthalmic solution |
| Stage 1 Cohort 1B: AGN-231868 High Dose | Experimental | Drug: AGN-231868Administration of AGN-231868 ophthalmic solution |
| Stage 1 Cohort 1B: AGN-231868 Vehicle | Placebo comparator | Other: AGN-231868 VehicleAdministration of matching placebo (vehicle) ophthalmic solution |
| Stage 2 Cohort 2: AGN-242428 High Dose | Experimental | Drug: AGN-242428Administration of AGN-242428 ophthalmic solution |
| Stage 2 Cohort 2: AGN-242428 Vehicle | Placebo comparator | Other: AGN-242428 VehicleAdministration of matching placebo (vehicle) ophthalmic solution |
| Stage 2 Cohort 2: AGN-231868 High Dose | Experimental | Drug: AGN-231868Administration of AGN-231868 ophthalmic solution |
| Stage 2 Cohort 2: AGN-231868 Vehicle | Placebo comparator | Other: AGN-231868 VehicleAdministration of matching placebo (vehicle) ophthalmic solution |
| Stage 2 Cohort 2: Lifitegrast Ophthalmic Solution | Active comparator | Drug: Lifitegrast 5% Ophthalmic SolutionAdministration of Lifitegrast ophthalmic solution |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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.
- 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;
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AGN-242428Ophthalmic solution administered as a topical eye drop | Drug | 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-231868Ophthalmic solution administered as a topical eye drop | Drug | 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 VehicleMatching placebo (vehicle) ophthalmic solution administered as a topical eye drop | Other | Stage 1 Cohort 1A: AGN-242428 Vehicle, Stage 1 Cohort 1B: AGN-242428 Vehicle, Stage 2 Cohort 2: AGN-242428 Vehicle |
| AGN-231868 VehicleMatching placebo (vehicle) ophthalmic solution administered as a topical eye drop | Other | Stage 1 Cohort 1A: AGN-231868 Vehicle, Stage 1 Cohort 1B: AGN-231868 Vehicle, Stage 2 Cohort 2: AGN-231868 Vehicle |
| Lifitegrast 5% Ophthalmic SolutionAlso: XiidraOphthalmic solution administered as a topical eye drop | Drug | Stage 2 Cohort 2: Lifitegrast Ophthalmic Solution |
Primary outcome
Stage 1: Number of Participants With Adverse Events
Time frame: Day 1 to Day 15
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.
Stage 1: Area Under the Plasma Concentration Versus Time Curves After Single and Repeat Dose Administration
Time frame: Day 2 and Day 15 (Predose and up to 12 hours postdose)
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.
Stage 1: Area Under the Tear Concentration Versus Time Curves After Single and Repeat Dose Administration
Time frame: Day 2 and Day 15 (Predose and up to 12 hours postdose)
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.
Stage 1: Maximum Plasma Drug Concentration (Cmax) After Single and Repeat Dose Administration
Time frame: Day 2 and Day 15 (Predose and up to 12 hours postdose)
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.
Stage 1: Maximum Tear Drug Concentration (Cmax) After Single and Repeat Dose Administration
Time frame: Day 2 and Day 15 (Predose and up to 12 hours postdose)
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.
Stage 1: Time of Maximum Plasma Drug Concentration (Tmax) After Single and Repeat Dose Administration
Time frame: Day 2 and Day 15 (Predose and up to 12 hours postdose)
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.
Stage 1: Time of Maximum Tear Drug Concentration (Tmax) After Single and Repeat Dose Administration
Time frame: Day 2 and Day 15 (Predose and up to 12 hours postdose)
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.
Stage 1: Terminal Elimination Half-life of the Study Drugs (T1/2) in Plasma After Single Dose Administration
Time frame: Day 2 (Predose and up to 12 hours postdose).
Following single dose administration, the plasma T1/2 (Day 2; Visit 3) was calculated.
Stage 1: Terminal Elimination Half-life of the Study Drugs (T1/2) in Plasma After Repeat Dose Administration
Time frame: Day 15 (Predose and up to 12 hours postdose)
Following repeat dose administration twice daily for 14 days, plasma T1/2 (Day 15; Visit 5) was calculated.
Stage 1: Terminal Elimination Half-life of the Study Drugs (T1/2) in Tear After Single and Repeat Dose Administration
Time frame: Day 2 and Day 15 (Predose and up to 12 hours postdose)
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.
Stage 1: Minimum Tear Drug Concentration at Steady State (Cmin,ss) After Repeat Dose Administration
Time frame: Day 15 (Predose and up to 12 hours postdose)
Following repeat dose administration twice daily for 14 days, the tear Cmin,ss (Visit 5) was calculated.
Stage 1: Minimum Plasma Drug Concentration at Steady State (Cmin,ss) After Repeat Dose Administration
Time frame: Day 15 (Predose and up to 12 hours postdose)
Following repeat dose administration twice daily for 14 days, the plasma Cmin,ss (Visit 5) was calculated.
Stage 1: Mean Accumulation Index of Drug Concentration (AI) After Repeat Dose Administration
Time frame: Day 15 (up to 12 hours) / Day 1 (up to 12 hours)
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.
Stage 1: Mean Drop Tolerability Questionnaire Scores
Time frame: Day 15
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.
Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values
Time frame: Day 1 to Day 15
The percentage of participants with non-PCS baseline value and met PCS criterion at least once postbaseline for clinical laboratory values.
Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature)
Time frame: Day 1 to Day 15
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)
Stage 1: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values
Time frame: Day 1 to Day 15
The percentage of participants with PCS postbaseline (but not at baseline) ECG values for QRS interval, PR interval, and QTc (Fridericia)
Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP)
Time frame: Day 1 to Day 15
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.
Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA)
Time frame: Day 1 to Day 15
BCVA was quantified using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity protocol.
Stage 1: Biomicroscopy: Percentage of Participants With Any Severity Increase From Baseline
Time frame: Day 1 to Day 15
The number of participants with any ophthalmoscopy findings of any severity increase from baseline at one or more visit.
Stage 1: Percentage of Participants With Any Clinically Significant Postbaseline Findings During Dilated Fundus Examination
Time frame: Day 1 to Day 15
The fundus (posterior pole; periphery, when dilated) was evaluated for pathology. Ophthalmoscopy with clinically significant findings (per investigator assessment) postbaseline are reported.
Stage 2: Number of Participants With Adverse Events
Time frame: Day 1 to Day 42
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.
Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values
Time frame: Day 42
The percentage of participants who have PCS postbaseline clinical laboratory values at Day 42 (Visit 6).
Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature)
Time frame: Day 42
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.
Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values
Time frame: Day 42
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.
Stage 2: Mean Change From Baseline in Intraocular Pressure (IOP)
Time frame: Day 1, Day 42
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.
Stage 2: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA)
Time frame: Day 1, Day 42
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.
Stage 2: Slit-lamp Biomicroscopy: Percentage of Participants With Any Clinically Significant Finding Postbaseline
Time frame: Day 1 to Day 42
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.
Stage 2: Percentage of Participants With Any Clinically Significant Postbaseline Findings During Dilated Fundus Examination
Time frame: Day 1 to Day 42
The fundus (posterior pole; periphery, when dilated) was evaluated for pathology. Ophthalmoscopy with clinically significant findings (per investigator assessment) postbaseline are reported.
Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment)
Time frame: Day 42 (Post-CAE)
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.
2 secondary outcomes
Stage 2: Trough Plasma Concentration (Ctrough) and Plasma Concentration at 0.5 Hours Postdose (C0.5h)
Time frame: Day 42
Stage 2: Trough Tear Concentration (Ctrough) and Tear Concentration at 0.5 Hours Postdose (C0.5h)
Time frame: Day 42
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42704415Tunon-Robinson I, Zheng S, Zhao C, Nguyen AK, Gomez-Freeman L. Selecting Vehicle Comparators in Dry Eye Disease Clinical Trials: Implications for Efficacy and Safety Assessment and Regulatory Outcomes. Ophthalmol Ther. 2026 Sep 7. doi: 10.1007/s40123-026-01490-2. Online ahead of print.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
ABBVIE INC. study director
AbbVie
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AGN-242428, AGN-231868 and Lifitegrast 5% Ophthalmic Solution in people with Dry Eye Disease and Dry Eye Syndrome, run by AbbVie at 11 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Stage 1: Number of Participants With Adverse Events (time frame: Day 1 to Day 15). The study lists 30 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04030962, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2025.