Clinical trial NCT03654885: XEN-45 Gel Stent Versus Trabeculectomy in Glaucoma: Gold-Standard Pathway Study (GPS)
Official title: XEN-45 Gel Stent Versus Trabeculectomy in Glaucoma: Gold-Standard Pathway Study (GPS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Glaucoma
Lead sponsor: Allergan
Sponsor class: INDUSTRY
First posted: 2018-08-31
Enrollment: 158
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: The purpose of this study is to compare the safety and efficacy of XEN-45 to trabeculectomy in participants with open angle glaucoma refractory to topical medical therapy.

Detailed description: This is a multi-center, randomized, parallel group, prospective, open-label clinical trial to evaluate the ability of XEN-45 to reduce intraocular pressure (IOP) and reduce the amount of topical IOP-lowering medications in participants poorly controlled on topical therapy. The planned study duration is 12 months. Participants were to be screened for enrollment and eligible candidates were to be approached to ascertain interest in study participation. Eligible participants were to be randomized 2:1; resulting in approximately 95 eyes implanted with XEN-45 and 44 eyes received trabeculetomy by study end.

Eligibility criteria: Inclusion Criteria:

* Open-angle glaucoma where the intraocular pressure (IOP) is not controlled when using topical IOP-lowering glaucoma medication
* Best-corrected baseline Snellen visual acuity of 20/100 or better
* Visual field mean deviation no worse than -18.0 decibels (dB)
* Medicated IOP ≥15 millimeter of mercury (mm Hg) and ≤44 mm Hg
* Participants not anticipated to require any ocular surgery (e.g., cataract surgery) in either eye up to 3 months from the time of inclusion
* Area of healthy, free, and mobile conjunctiva in the target area (superior bulbar conjunctiva)
* Trabecular meshwork must be visible (with Shaffer angle grade ≥2 in the target quadrant)
* Failed ab-interno canal or suprachoroidal micro invasive glaucoma surgery (MIGS) procedures (such as i-Stent, gonioscopy-assisted transluminal trabeculotomy \[GATT\], Ab-interno canaloplasty \[ABiC\], Kahook dual blade goniotomy, etc.) are allowed ≥3 months before enrollment. CyPass® Micro-Stents were not allowed.

Exclusion Criteria:

* Participant has active neovascular, uveitic or angle recession glaucoma or any glaucoma associated with vascular disorders
* Participant has had prior ab externo incisional glaucoma surgery (such as trabeculectomy, viscocanalostomy, canaloplasty, tube shunts of any type, collagen implants, etc.), conjunctival filtering surgery, transscleral cycloablative procedures (such as cyclophotocoagulation, micro pulse cyclophotocoagulation, cryotherapy, ultrasound circular cyclocoagulation \[UC3\], etc.) or prior major conjunctival surgery (i.e., scleral buckle)
* Clinically significant inflammation or infection within 30 days before the preoperative visit (e.g., blepharitis, conjunctivitis, severe ocular surface disease, keratitis, uveitis, herpes simplex infection)
* Presence of conjunctival scarring or prior conjunctival surgery or other conjunctival pathologies (e.g., pterygium) in the target area
* History of corneal surgery, corneal opacities, or corneal disease
* Central corneal thickness ≤490 micrometer (μm) or ≥620μm
* Vitreous present in the anterior chamber
* Aphakic
* Participant has had prior intraocular surgery in either eye within ≤3 months before the preoperative visit (including phacoemulsification)
* History of complicated cataract surgery (e.g. with visual impairment, e.g. vitreous loss, anterior chamber intraocular lens \[ACIOL\], perhaps sutured intraocular lens \[IOL\] or scleral fixated IOL, prior cystoid macular edema \[CME\], etc.)
* Presence of intraocular silicone oil
* Active diabetic retinopathy, proliferative retinopathy, choroidal neovascularization, branch retinal vein occlusion, central retinal vein occlusion, geographic atrophy, or other ophthalmic disease or disorder that could confound study results or impaired episcleral venous drainage (e.g., Sturge-Weber or nanophthalmos, Axenfeld-Reiger, iridocorneal endothelial syndrome \[ICE\], etc.)
* Known or suspected allergy or sensitivity to drugs required for the protocol (including anesthesia), or any of the device components (e.g., bovine or porcine products, or glutaraldehyde)
* Pregnant or nursing women and those planning a pregnancy during the study period.
* Participation in another drug or device clinical trial concluding within 30 days before the preoperative visit

Primary outcomes:
measure: Percentage of Participants Achieving at Least 20% Intraocular Pressure (IOP) Reduction (Improvement) From Baseline at Month 12 With Prespecified Caveats
timeFrame: Baseline (Preoperative) to Month 12
Secondary outcomes:
measure: Mean IOP Over Time
timeFrame: Baseline and Day 1, Weeks 1 and 2, Months 1, 3, 6, 9, and 12
measure: Change From Baseline in Mean IOP Over Time
timeFrame: Baseline and Day 1, Weeks 1 and 2, Months 1, 3, 6, 9, and 12
measure: Mean Number of Topical IOP-Lowering Medications Over Time
timeFrame: Baseline and Day 1, Weeks 1 and 2, Months 1, 3, 6, 9, and 12
measure: Change From Baseline in Mean Number of Topical IOP-Lowering Medications Over Time
timeFrame: Baseline and Day 1, Weeks 1 and 2, Months 1, 3, 6, 9, and 12
measure: Change From Baseline in Mean IOP at Month 12
timeFrame: Baseline (Preoperative) and Month 12
measure: Change From Baseline in Mean Number of Topical IOP-Lowering Medications at Month 12
timeFrame: Baseline (Preoperative) and Month 12
measure: Change in Mean IOP From Preoperative Baseline Over Time in Participants With Eyes With Baseline IOP ≤18 mm Hg
timeFrame: Baseline (Preoperative) and Month 12
measure: Change in Number of Topical IOP-Lowering Medications From Preoperative Baseline to Month 12 in Participants With Eyes With Baseline IOP ≤18 mm Hg
timeFrame: Baseline (Preoperative) and Month 12
measure: Percentage of Participants Achieving Specific IOP Targets at Month 12
timeFrame: Month 12
measure: Percentage of Participants Achieving Specific Percentage IOP Lower Targets From Baseline at Month 12
timeFrame: Baseline (Preoperative) to Month 12
measure: Percentage of Participants Achieving at Least a 20% IOP Reduction and Specific IOP Targets on Same or Lower Number of Topical IOP-Lowering Medications at Month 12
timeFrame: Baseline (Preoperative) and Month 12
measure: Percentage of Participants With Needlings Performed
timeFrame: Up to Month 12
measure: Mean Number of Needlings Per Eye
timeFrame: Up to Month 12
measure: Percentage of Eyes Achieving at Least a 20% Reduction in IOP at Month 12 on the Same or Fewer Topical IOP-lowering Medications in Participants Who Had Needlings
timeFrame: Month 12
measure: Percentage of Eyes Not Using Any Topical IOP-lowering Medications in Participants Who Had Needlings
timeFrame: Month 12
measure: Percentage of Participants With Antifibrotic Use During Needling
timeFrame: Up to Month 12
measure: Percentage of Participants Achieving Complete Success at Month 12
timeFrame: Month 12
measure: Percentage of Participants Achieving Qualified Success at Month 12
timeFrame: Month12
measure: Percentage of Participants Achieving Specific IOP Targets at Month 12 in Medication-free Eye
timeFrame: Month 12
measure: Percentage of Participants Achieving Specific Percentage IOP Lower Targets From Baseline at Month 12 With Medication-free Eyes
timeFrame: Month 12
measure: Percentage of Participants With Intraoperative Adjunctive Antifibrotic Therapy Use
timeFrame: Month 12
measure: Percentage of Participants With Intraoperative Adjunctive Antifibrotic Therapy Based on Time of Administration
timeFrame: Month 12
measure: Percentage of Participants With Different Modes of Administration of Intraoperative Adjunctive Antifibrotic Therapy
timeFrame: Month 12
measure: Percentage of Participants With Different Volumes of Intraoperative Adjunctive Antifibrotic Therapy
timeFrame: Month 12
measure: Percentage of Participants With Different Concentrations for Intraoperative Adjunctive Antifibrotic Therapy
timeFrame: Month 12
measure: Percentage of Participants With Different Absolute Dose for Intraoperative Adjunctive Antifibrotic Therapy
timeFrame: Month 12
measure: Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) With Current Glasses
timeFrame: Baseline and Day 1, Weeks 1 and 2, and Months 1, 3, 6, 9, and 12
measure: Mean Change From Baseline in Manifest Refraction - Mean Visual Acuity Using Snellen Eye Chart in LogMAR Scale
timeFrame: Baseline (Preoperative) and postoperative Months 1, 3, 6, and 12
measure: Mean Surgically Induced Astigmatism - Autorefractor Reading
timeFrame: Month 12
measure: Mean Change From Baseline in Surgically Induced Astigmatism - Autorefractor Reading
timeFrame: Baseline (Preoperative) and Month 12
measure: Mean Change From Baseline in Surgically Induced Astigmatism - Topography at Selected Sites
timeFrame: Baseline (Preoperative), Week 1, and Months 1 and 12
measure: Mean Change From Baseline in Optical Biometry - Anterior Chamber Depth
timeFrame: Baseline, Day 1 and Week 2
measure: Mean Change in From Baseline Optical Biometry - Keratometry (K)1, K2, Delta D
timeFrame: Baseline, Day 1 and Week 2
measure: Bleb Morphology - Anterior Segment Optical Coherence Tomography (AS-OCT) at Selected Sites
timeFrame: Up to Month 12
measure: Bleb Morphology - Slit Lamp Photography at Selected Sites
timeFrame: Up to Month 12
measure: Percentage of Participants With Clinical Hypotony
timeFrame: Month 12
measure: Percentage of Eyes With IOP 6 mm Hg or Less at Any Time Point and Relevant Clinical Assessment
timeFrame: Up to Month 12
measure: Percentage of Participants With Specific Intraoperative Adverse Events of Special Interest (AESIs)
timeFrame: Median follow-up of 366.0 days
measure: Percentage of Participants With Postoperative Treatment-Emergent Adverse Events of Special Interest (AESIs)
timeFrame: Median follow-up of 366.0 days
measure: Percentage of Participants With BCVA Worst Line Change From Baseline Across Follow-Up
timeFrame: Baseline up to Month 12
measure: Pachymetry Based on Change From Baseline In Average Central Corneal Thickness
timeFrame: Baseline (Preoperative) and Month 12
measure: Change From Baseline in Visual Field Examinations Analyzed by Machine Type
timeFrame: Baseline and Month 12
measure: Percentage of Participants With at Least One Adverse Event (AE), Serious Adverse Events (SAEs), Adverse Device Effects (ADEs) and Serious ADEs (SADEs)
timeFrame: Median follow-up of 366.0 days
measure: Patient-reported Outcomes (PRO): Change From Baseline in Symptom and Health Problem Checklist (SHPC-18) Scores
timeFrame: Baseline (Preoperative) to Month 6
measure: PRO: Percentage of Participants With Post-Surgical Resumption of Activities and Daily Routine
timeFrame: Month 3
measure: PRO: Percent Change From Baseline in Work Productivity and Activity Impairment (WPAI): Percent Overall Work Impairment Due to Health
timeFrame: Baseline (Preoperative) and Month 12
measure: PRO: Percent Change From Baseline in WPAI: Percent Activity Impairment Due to Health
timeFrame: Baseline (Preoperative) and Month 12
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Vold Vision /ID# 233677
state: Arkansas
city: Arcadia
country: United States
facility: Retina Institute of California /ID# 233692
state: California
city: Culver City
country: United States
facility: Angeles Eye Institute /ID# 233632
state: California
city: Los Angeles
country: United States
facility: Cha Medical Group Pc /Id# 233649
state: California
city: Sacramento
country: United States
facility: Grutzmacher Lewis and Sierra Inc. /ID# 233654
state: California
city: Denver
country: United States
facility: University of Colorado Denver /ID# 233676
state: Colorado
city: Washington
country: United States
facility: Howard University Hospital /ID# 233615
state: District of Columbia
city: Hollywood
country: United States
facility: Eye Surgery Associates /ID# 233638
state: Florida
city: Weston
country: United States
facility: Specialty Retina Center /ID# 233628
state: Florida
city: Atlanta
country: United States
facility: Georgia Eye Partners /ID# 233655
state: Georgia
city: Roswell
country: United States
facility: Coastal Research Associates /ID# 233575
state: Georgia
city: Honolulu
country: United States
facility: Tyrie Lee Jenkins MD Inc. /ID# 233674
state: Hawaii
city: Peoria
country: United States
facility: Illinois Eye Center /ID# 233631
state: Illinois
city: Overland Park
country: United States
facility: Stiles Eyecare Excellence /ID# 233583
state: Kansas
city: Reading
country: United States
facility: Advanced Glaucoma Specialists /ID# 233690
state: Massachusetts
city: Ann Arbor
country: United States
facility: Kellogg Eye Center University of Michigan health system /ID# 233651
state: Michigan
city: Saint Paul
country: United States
facility: Mayo Clinic Jacksonville /ID# 233634
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University in St. Louis /ID# 233599
state: Missouri
city: Slingerlands
country: United States
facility: Glaucoma associates/consultants of the capital region /ID# 233695
state: New York
city: Southern Pines
country: United States
facility: Carolina Eye Associates /ID# 233656
state: North Carolina
city: Youngstown
country: United States
facility: Eye Care Associates Inc /ID# 233636
state: Ohio
city: Oklahoma City
country: United States
facility: Dean McGee Eye Institute /ID# 233595
state: Oklahoma
city: Chambersburg
country: United States
facility: Ludwick Eye Center /ID# 233691
state: Pennsylvania
city: King Of Prussia
country: United States
facility: Kremer Eye Center /Id# 233642
state: Pennsylvania
city: Philadelphia
country: United States
facility: Wills Eye Institute /ID# 233645
state: Pennsylvania
city: Pittsburgh
country: United States
facility: university of Pittsburgh /ID# 233622
state: Pennsylvania
city: Florence
country: United States
facility: Carolinas Centers for Sight,PC /ID# 233606
state: South Carolina
city: Nashville
country: United States
facility: Nashville Vision Associates /ID# 233644
state: Tennessee
city: Dallas
country: United States
facility: Glaucoma Associates of Texas /ID# 233587
state: Texas
city: El Paso
country: United States
facility: El Paso Eye Surgeons, P.A. /ID# 233584
state: Texas
city: Houston
country: United States
facility: Houston Eye Associates /ID# 233621
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine - Baylor Medical Center /ID# 233612
state: Texas
city: Roanoke
country: United States
facility: Vistar Eye Center /ID# 233652
state: Virginia
city: Madison
country: United States
facility: SSM Health Dean Medical Group /ID# 233624
state: Wisconsin
city: Racine
country: United States
facility: The Eye Centers of Racine and Kenosha LTD /ID# 233657
state: Wisconsin
Study officials:
affiliation: Allergan
name: ALLERGAN INC.
role: STUDY_DIRECTOR
References: