PRM-151 in the Prevention of Scarring Following Trabeculectomy

A Randomized, Double-Masked, Placebo-Controlled Study of PRM-151 in the Prevention of Postoperative Scarring in Glaucoma Patients Following Primary Trabeculectomy

This study will assess the safety and tolerability of PRM-151 administered as a subconjunctival injection and explore the effect of PRM-151 on various correlates of the wound healing process that occurs in the eye after glaucoma filtration surgery.

Study Overview

• Status: Completed
• Conditions: Glaucoma
• Intervention / Treatment: Drug: PRM-151; Drug: Placebo

Detailed Description

Glaucoma is a disease of the eye which affects the optic nerve (the nerve that sends signals from the eye to the brain) and is associated with visual field defects and potential blindness. The treatment of glaucoma involves lowering the pressure in the eye, which is often (but not always) elevated due to accumulation of fluid inside the eye that cannot drain away. In the operation called trabeculectomy (a type of filtration surgery), a small channel is created through the sclera (the white of the eye) to allow accumulated fluid to drain away. Scarring may occur after surgery when, during healing, too much collagen (a type of protein) is deposited in the channel. This causes the channel to seal up and the pressure inside the eye to build up again.

The study will be conducted in patients suffering from glaucoma who are due to undergo trabeculectomy. Patients will be randomized to have either PRM-151 or placebo.

• Study Type: Interventional
• Enrollment (Actual): 124
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, B-3000
    • University Hospital Leuven
• Czechia
  • Brno, Czechia, 639 00
    • Oftalmologicka klinika Brno-Bohunice
  • Hradec Kralove, Czechia, 500 05
    • Facility Hospital Hradec Kralove
  • Olomouc, Czechia, 775 20
    • Palacky University
  • Pardubice, Czechia, 53203
    • Hospital Pardubice
  • Praha, Czechia
    • Charles University
  • Usti' Nad/Labem, Czechia, 40013
    • Masaryak's Hospital
• Netherlands
  • Nijmegen, Netherlands, 6525 EX
    • UMC St. Radboud West
  • Rotterdam, Netherlands, 3015 CE
    • Eramus Medical Center
• United Kingdom
  • Gloucestershire, United Kingdom, GL53 7AN
    • Cheltenham General Hospital
  • London, United Kingdom
    • St. Thomas
  • Norwich, United Kingdom, NR4 7UY
    • Norfolk and Norwich University Hospital-NHS Trust
  • Oxford, United Kingdom, OX3 9DU
    • Oxford Eye Hosiptal
  • Sheffield, United Kingdom, S10 2JF
    • Royal Hallamshire Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men or women of nonchildbearing potential (WONCBP) aged 18 years and older at screening.
• Diagnosis of chronic angle-closure glaucoma or open-angle glaucoma, phakic or pseudophakic, with visual field or optic disc changes characteristic of glaucoma. For pseudophakic glaucoma patients, the cataract surgery performed was with phacoemulsification and through a corneal incision.
• Suitable candidate for trabeculectomy in the study eye which the physician deems as medically necessary.

Exclusion Criteria:

• Diagnosis of glaucoma other than chronic angle-closure glaucoma or open-angle glaucoma (ie., uveitic, traumatic or neovascular glaucoma).
• Any previous ocular surgeries in the study eye involving the upper conjunctiva and sclera.
• History of laser surgeries in the study eye within 90 days before day 1.
• Presence or history of any disease that could affect wound healing.
• Any asymmetric abnormality of the anterior segment which requires additional intervention (surgery or medication).
• Any abnormality other than glaucoma in the study eye that could affect tonometry.
• Presence or history of uveitis within 10 years or any other ocular infection or inflammation within 14 days before day 1.
• Clear corneal phacoemulsification performed within 90 days before day 1.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo solution (0.1 mL volume) by subconjunctival injection Days 1 (immediately following trabeculectomy), 2, 3, 5 and 9
Experimental: PRM-151; PRM-151 (recombinant human serum amyloid P, recombinant human pentraxin 2)	Drug: PRM-151; PRM-151 2 milligrams (mg) (0.1 mL volume) by subconjunctival injection Days 1 (immediately following trabeculectomy), 2, 3, 5 and 9; Other Names: recombinant human serum amyloid P; recombinant human pentraxin 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of Subconjunctival Injection	Number of adverse events (AEs), treatment emergent adverse events (TEAEs), non-ocular TEAEs, Ocular TEAEs, serious adverse events (SAEs), abnormal slit-lamp biomicroscopic findings, and abnormal dilated fundoscopy findings	AEs, slit-lamp, and fundoscopy findings from first injection through end of study; TEAEs from first injection through Day 30
Subjects With Safety Related Events or Findings	The number of Subjects with AEs, TEAEs, SAEs, decreased visual acuity, and worsened visual fields	First injection through end of study for AEs, SAEs, visual acuity and visual fields, and from first injection through Day 30 for TEAEs

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Successful Intra-ocular Pressure (IOP) Control	Exploratory efficacy outcome measure. Successful IOP control defined as IOP between 6 and 18 mm Hg or 25% reduction from pre-surgical IOP	Day 120
Bleb Scarring	Exploratory Efficacy Outcome measure: Bleb scarring is graded on a scale from 0-3. 0= none to minimal scarring, 1= mild, 2= moderate, 3= severe scarring.	Day 120

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Jeffrey Edelson, MD, FRCPC, MHSc, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2010
• Primary Completion (Actual): April 30, 2012
• Study Completion (Actual): November 14, 2012

Study Registration Dates

• First Submitted: February 5, 2010
• First Submitted That Met QC Criteria: February 5, 2010
• First Posted (Estimate): February 8, 2010

Study Record Updates

• Last Update Posted (Actual): April 28, 2022
• Last Update Submitted That Met QC Criteria: March 31, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: glaucoma, trabeculectomy
• Additional Relevant MeSH Terms: Eye Diseases; Ocular Hypertension; Glaucoma
• Other Study ID Numbers: GA42405; PRM151B-21GL (Other Identifier: Promedior, Inc.); 2009-017859-98 (EudraCT Number)