Ocular Surface Disease, Open-Angle Glaucoma or Ocular Hypertension
Conditions
Keywords
IOP, OSD
Brief summary
A Phase III, Multinational, Multicenter, Investigator-Masked, Randomized, Active-Controlled Trial, comparing the efficacy and safety of DE-130A with Xalatan® in Patients with Open-Angle Glaucoma or Ocular Hypertension over a 3-Month period, followed by a 12-Month Follow-Up with Open-Label DE-130A Treatment.
Detailed description
Phase III, prospective, interventional, multinational, multicentre, investigator-masked, randomized, active-controlled trial Study duration: * 5 days to 5-week washout period * 15 months for the first 130 patients * 12 weeks for the next 250 patients Patients will attend 6 visits following the wash-out phase (up to 5 weeks): * Period 1 (3-month investigator-masked treatment period, DE-130A vs Xalatan®): Randomization/Baseline visit (Day 1), Week 4 (±3 days) and Week 12 (±3 days) * Period 2 (12-month follow-up from Week 12, open-label DE-130A treatment for the first 130 patients who complete their week 12 visit and agree to participate in the open-label period of the study): Month 6 (± 7days), Month 9 (±7 days) and Month 15 (± 1 week) visits.
Interventions
DRUGDE-130A/DE-130A
After Week 12, received DE-130A continuously.
DRUGXalatan®/DE-130A
From week 12 onwards, DE-130A was continued to be administered instead of Xalatan®.
DRUGDE-130A
Latanoprost 50 microg/ml eye drops emulsion, preservative-free eye drops emulsion in single-dose containers.
DRUGXalatan®
Latanoprost 50 microg/ml eye drops solution, eye drops in 2.5 ml dropper containers.
Sponsors
Santen SAS
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female, 18 years of age or older 2. The patient has signed and dated a written informed consent form and any required privacy authorization prior to the conduct of any study procedures. 3. Diagnosis of OAG (primary open angle glaucoma, pseudo exfoliative glaucoma, or pigmentary glaucoma), or OHT in eligible eye(s) currently on monotherapy. 4. Unilateral OAG, or OHT are permissible as long as the physician does not anticipate significant IOP changes to the fellow eye that would require treatment during the duration of the study. 5. Current treatment with monotherapy for OAG or OHT with a controlled IOP ≤ 18 mmHg in each eye (pre-washout). 6. Stable visual field (based on at least two visual fields available within the last 18 months prior to screening, including one in the last 6 months; A visual field test will be performed at screening if not already performed within the last 6 months prior to screening) in each eye. 7. Post-washout IOP ≥ 22 mmHg in at least one eye (defined at baseline visit \[Day 1\] by IOP measurement at both 9:00 am ± 1 hour and 4:00 pm ±1 hour) 8. Post-washout IOP ≤ 32 mmHg (defined at baseline visit \[Day 1\] by IOP measurement at both 9:00 am ±1 hour and 4:00 pm ±1 hour) in both eyes. 9. Ability to discontinue their current topical IOP-lowering medication for the required washout period. Washout periods should be as follows; * Prostaglandin analogs = 4 weeks * Topical beta blockers ≥ 3 weeks and ≤ 4 weeks * Topical carbonic anhydrase inhibitors ≥ 5 days and ≤ 4 weeks * All other IOP lowering medication ≥ 2 weeks and ≤ 4 weeks 10. Snellen best corrected visual acuity score of 20/100 or better in each eye 11. Patient must be willing to discontinue wearing contact lenses during the study. 12. Adequate health for study participation as determined by the investigator 13. In the opinion of the investigator, the patient is capable of understanding and complying with protocol requirements 14. Patient must be willing and able to undergo and return for scheduled study-related examinations. \-
Exclusion criteria
1. Any form of glaucoma other than primary open angle glaucoma, pseudo exfoliative glaucoma, and pigmentary glaucoma in either eye. 2. IOP at any time point during the Screening or Baseline visits (Visits 1 or 2) of \> 32 mmHg in either eye. 3. Current treatment for glaucoma with a fixed-combination therapy or more than one drug in either eye or with an oral drug within 6 months prior to screening. 4. Corneal abnormalities that would interfere with accurate IOP readings with an applanation tonometer in either eye. 5. Central corneal thickness ≤ 480 µm or ≥ 600 µm in either eye (historical data or at the screening visit). 6. Significant visual field loss (absolute defect in the 10° central point or mean deviation worse than -12 dB) or progressive field loss during the year before screening in either. 7. Significant optic nerve abnormality, other than glaucomatous abnormalities in the opinion of the investigator as determined by ophthalmoscopy in either eye. 8. Significant changes of the optic neuropathy (e.g. increase cupping since the last examination, optic nerve hemorrhage) in either eye. 9. Inability to visualize the patient's optic nerve in either eye. 10. Gonioscopy consistent with potential angle closure glaucoma in either eye. 11. Patients with severe blepharitis and/or Meibomian Gland Disease (MGD). Patients enrolled with mild to moderate blepharitis and/or MGD should be treated as appropriate during the study in either eye. 12. Use of oral or topical ophthalmic steroid within the past 14 days from screening date, or anticipated need for ocular steroid treatment during the study in either eye. 13. Use of intravitreal or peribulbar injection of depot steroid or placement of an intravitreal steroid implant within the past 3 months from screening date in either eye. 14. Known allergy or sensitivity to the study medications. 15. Active or expected ocular allergy during period 1. 16. Any active ocular disease (e.g. uveitis, ocular infection, severe dry eye with CFS grade 4 or more on the modified Oxford scale) in either eye. Patients may have mild cataracts, age-related maculopathy or background diabetic retinopathy if, in the opinion of the Investigator, it would not interfere with the conduct of the study. 17. Intraocular surgery within 6 months prior to screening in either eye. 18. Past history of any filtering surgery for glaucoma in either eye. 19. Refractive surgery of any type within 1 year prior to screening in either eye. 20. Uncontrolled systemic disease of any type. 21. Anticipated alteration in chronic therapy with or introduction of agents known to have a substantial effect on IOP (e.g., alpha-adrenergic agonists, beta-adrenergic antagonists, calcium channel blockers, ACE inhibitors and/or angiotensin II receptor blockers), unless the subject and the medication dosage have been stable for three months prior to the screening visit and the dosage is not expected to change during the study. 22. Anticipated change in dosage of or introduction of new medications for chronic cardiac, pulmonary or hypertensive conditions. 23. Females who are pregnant or lactating and females of child-bearing potential who are not using a medically acceptable, highly effective method of birth control. 24. Current enrolment in an investigational drug or device study or participation in such a study within 30 days prior to screening. 25. History of drug or alcohol abuse. 26. Patient has any condition or situation that, in the Investigator's opinion, might confound the results of the study, may put the patient at significant risk or might interfere with the patient's ability to participate in the study. \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Intraocular Pressure (IOP) Change (mmHg) at Week 12 | Week 12 (09:00) peak timepoint | Intraocular Pressure (IOP) change from baseline peak (mmHg). IOP was measured using calibrated Goldman applanation tonometer in the morning (9:00 am ± 1 hour). Analysis using Mixed-Effects Model for Repeated Measures (MMRM). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Corneal Fluorescein Staining (CFS) Change From Baseline (First Key Secondary Endpoint) | Week 12 | CFS Change from baseline in participants with baseline CFS score ≥ 1 at Week 12 Staining using fluorescein were graded using the Modified Oxford scale (7-point ordinal scale, score 0, 0.5, and 1 to 5 per area for cornea and conjunctiva separately) as shown below: * Score = 0: No staining dots * Score = 0.5: One staining dot per area * Score = 1: More staining dot per area than score 0.5 * Score = 2: More staining dot per area than score 1 * Score = 3: More staining dot per area than score 2 * Score = 4: More staining dot per area than score 3 * Score = 5: More staining dot per area than score 4 A Mixed-Effects Model for Repeated Measures (MMRM) was fitted to the CFS change from baseline at each visit. |
| Ocular Surface Disease (OSD) Symptoms (Average of 3 Symptoms); Second Key Secondary Endpoint | Week 12 | Change from baseline in OSD symptom score (average of 3 symptoms: dry eye sensation, blurred/poor vision and burning/stinging/itching) in the study eye at Week 12 in patients with baseline symptom average score\>0. Ocular symptoms were graded on a 5-point scale as shown below: * Scale = 0: Absent * Scale = 1: Mild * Scale = 2: Moderate * Scale = 3: Severe * Scale = 4: Very severe Least Square Means and p-values were obtained by fitting a Mixed-Effects Model for Repeated Measures (MMRM) model to the Ocular Surface Disease (OSD) average change from baseline at each visit. |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| DE-130A DE-130A: Latanoprost 50 microg/ml preservative-free eye drops emulsion, eye drops emulsion in single-dose containers.
Instillation of one drop, once daily in the evening (9 pm ±1 hour) in the conjunctival sac of the affected eye(s). Both eyes will be treated unless the patient suffers from unilateral OAG/OHT | 193 |
| Xalatan® Xalatan®: Latanoprost 50 microg/ml eye drops solution, eye drops in 2.5 ml dropper containers.
Instillation of one drop, once daily in the evening (9 pm ± 1 hour) in the conjunctival sac of the affected eye(s). Both eyes will be treated unless the patient suffers from unilateral OAG/OHT | 193 |
| Total | 386 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period 1 Double Masked Treatment Period | Adverse Event | 1 | 1 | 0 | 0 |
| Period 1 Double Masked Treatment Period | Death | 1 | 0 | 0 | 0 |
| Period 1 Double Masked Treatment Period | Sponsor Temporarily Discontinued Study | 0 | 1 | 0 | 0 |
| Period 1 Double Masked Treatment Period | Withdrawal by Subject | 1 | 1 | 0 | 0 |
| Period 2 Open Label Treatment Period | Adverse Event | 0 | 0 | 0 | 2 |
| Period 2 Open Label Treatment Period | Early Termination | 0 | 0 | 1 | 0 |
| Period 2 Open Label Treatment Period | Pregnancy | 0 | 0 | 1 | 0 |
| Period 2 Open Label Treatment Period | Withdrawal by Subject | 0 | 0 | 2 | 2 |
Baseline characteristics
| Characteristic | DE-130A | Total | Xalatan® |
|---|---|---|---|
| Age, Categorical Double Masked Period <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Double Masked Period >=65 years | 90 Participants | 188 Participants | 98 Participants |
| Age, Categorical Double Masked Period Between 18 and 65 years | 102 Participants | 196 Participants | 94 Participants |
| Age, Continuous Double Masked Period | 62.3 years STANDARD_DEVIATION 12.07 | 63.1 years STANDARD_DEVIATION 11.16 | 63.9 years STANDARD_DEVIATION 10.14 |
| Race (NIH/OMB) Double Masked Period American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Double Masked Period Asian | 4 Participants | 8 Participants | 4 Participants |
| Race (NIH/OMB) Double Masked Period Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Double Masked Period More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Double Masked Period Native Hawaiian or Other Pacific Islander | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Double Masked Period Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Double Masked Period White | 184 Participants | 370 Participants | 186 Participants |
| Region of Enrollment Austria | 5 participants | 7 participants | 2 participants |
| Region of Enrollment Belgium | 5 participants | 11 participants | 6 participants |
| Region of Enrollment Estonia | 13 participants | 29 participants | 16 participants |
| Region of Enrollment Finland | 3 participants | 5 participants | 2 participants |
| Region of Enrollment France | 4 participants | 4 participants | 0 participants |
| Region of Enrollment Germany | 7 participants | 15 participants | 8 participants |
| Region of Enrollment Italy | 19 participants | 37 participants | 18 participants |
| Region of Enrollment Latvia | 14 participants | 26 participants | 12 participants |
| Region of Enrollment Poland | 4 participants | 9 participants | 5 participants |
| Region of Enrollment Russia | 89 participants | 181 participants | 92 participants |
| Region of Enrollment South Korea | 3 participants | 6 participants | 3 participants |
| Region of Enrollment Spain | 19 participants | 43 participants | 24 participants |
| Region of Enrollment United Kingdom | 8 participants | 13 participants | 5 participants |
| Sex: Female, Male Double Masked Period Female | 120 Participants | 236 Participants | 116 Participants |
| Sex: Female, Male Double Masked Period Male | 72 Participants | 148 Participants | 76 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 193 | 0 / 193 | 0 / 71 | 0 / 66 |
| other Total, other adverse events | 35 / 193 | 42 / 193 | 21 / 71 | 21 / 66 |
| serious Total, serious adverse events | 1 / 193 | 2 / 193 | 0 / 71 | 0 / 66 |
Outcome results
Primary
Intraocular Pressure (IOP) Change (mmHg) at Week 12
Intraocular Pressure (IOP) change from baseline peak (mmHg). IOP was measured using calibrated Goldman applanation tonometer in the morning (9:00 am ± 1 hour). Analysis using Mixed-Effects Model for Repeated Measures (MMRM).
Time frame: Week 12 (09:00) peak timepoint
Population: Full Analysis Set (FAS) included all randomized subjects who received at least one dose of the study medication and provided at least one post-baseline IOP measurement at peak and trough timepoints separately. The number analyzed are participants evaluable for the outcome measure at Week 12 (09:00) timepoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| DE-130A | Intraocular Pressure (IOP) Change (mmHg) at Week 12 | -8.8 mmHg | Standard Error 0.25 |
| Xalatan® | Intraocular Pressure (IOP) Change (mmHg) at Week 12 | -8.2 mmHg | Standard Error 0.26 |
Primary
Intraocular Pressure (IOP) Change (mmHg) at Week 12
Intraocular Pressure (IOP) change from baseline trough (mmHg). IOP was measured using calibrated Goldman applanation tonometer in the afternoon (4:00 pm ± 1 hour). Analysis using Mixed-Effects Model for Repeated Measures (MMRM).
Time frame: Week 12 (16:00) trough timepoint
Population: Full Analysis Set (FAS) included all randomized subjects who received at least one dose of the study medication and provided at least one post-baseline IOP measurement at peak and trough timepoints separately. The number analyzed are participants evaluable for the outcome measure at Week 12 (16:00) timepoint.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| DE-130A | Intraocular Pressure (IOP) Change (mmHg) at Week 12 | -8.6 mmHg | Standard Error 0.24 |
| Xalatan® | Intraocular Pressure (IOP) Change (mmHg) at Week 12 | -8.1 mmHg | Standard Error 0.25 |
Secondary
Corneal Fluorescein Staining (CFS) Change From Baseline (First Key Secondary Endpoint)
CFS Change from baseline in participants with baseline CFS score ≥ 1 at Week 12 Staining using fluorescein were graded using the Modified Oxford scale (7-point ordinal scale, score 0, 0.5, and 1 to 5 per area for cornea and conjunctiva separately) as shown below: * Score = 0: No staining dots * Score = 0.5: One staining dot per area * Score = 1: More staining dot per area than score 0.5 * Score = 2: More staining dot per area than score 1 * Score = 3: More staining dot per area than score 2 * Score = 4: More staining dot per area than score 3 * Score = 5: More staining dot per area than score 4 A Mixed-Effects Model for Repeated Measures (MMRM) was fitted to the CFS change from baseline at each visit.
Time frame: Week 12
Population: The number analyzed are participants evaluable for the outcome measure at Week 12 with CFS change from baseline in participants with baseline CFS score ≥ 1. Data were obtained by fitting a Mixed-Effects Model for Repeated Measures (MMRM) to the CFS change from baseline at each visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| DE-130A | Corneal Fluorescein Staining (CFS) Change From Baseline (First Key Secondary Endpoint) | -0.71 score | Standard Error 0.069 |
| Xalatan® | Corneal Fluorescein Staining (CFS) Change From Baseline (First Key Secondary Endpoint) | -0.41 score | Standard Error 0.077 |
Secondary
Ocular Surface Disease (OSD) Symptoms (Average of 3 Symptoms); Second Key Secondary Endpoint
Change from baseline in OSD symptom score (average of 3 symptoms: dry eye sensation, blurred/poor vision and burning/stinging/itching) in the study eye at Week 12 in patients with baseline symptom average score\>0. Ocular symptoms were graded on a 5-point scale as shown below: * Scale = 0: Absent * Scale = 1: Mild * Scale = 2: Moderate * Scale = 3: Severe * Scale = 4: Very severe Least Square Means and p-values were obtained by fitting a Mixed-Effects Model for Repeated Measures (MMRM) model to the Ocular Surface Disease (OSD) average change from baseline at each visit.
Time frame: Week 12
Population: The number analyzed are participants evaluable for the outcome measure at Week 12 with change from baseline in OSD symptom score\>0 (average of 3 symptoms).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| DE-130A | Ocular Surface Disease (OSD) Symptoms (Average of 3 Symptoms); Second Key Secondary Endpoint | -0.26 score | Standard Error 0.058 |
| Xalatan® | Ocular Surface Disease (OSD) Symptoms (Average of 3 Symptoms); Second Key Secondary Endpoint | -0.17 score | Standard Error 0.06 |