Clinical trial NCT04133311: 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
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Open-Angle Glaucoma or Ocular Hypertension
Ocular Surface Disease
Keywords: IOP
OSD
Lead sponsor: Santen SAS
Sponsor class: INDUSTRY
First posted: 2019-10-21
Enrollment: 386
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

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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.

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Primary outcomes:
measure: Intraocular Pressure (IOP) Change (mmHg) at Week 12
timeFrame: Week 12 (09:00) peak timepoint
measure: Intraocular Pressure (IOP) Change (mmHg) at Week 12
timeFrame: Week 12 (16:00) trough timepoint
Secondary outcomes:
measure: Corneal Fluorescein Staining (CFS) Change From Baseline (First Key Secondary Endpoint)
timeFrame: Week 12
measure: Ocular Surface Disease (OSD) Symptoms (Average of 3 Symptoms); Second Key Secondary Endpoint
timeFrame: Week 12
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital des XV-XX
state: Île-de-France
Study officials:
affiliation: Santen SAS
name: Jean-Sebastien Garrigue, PhD
role: STUDY_CHAIR
References: