Glaucoma
Conditions
Keywords
glaucoma, trabeculectomy
Brief summary
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.
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.
Interventions
DRUGPRM-151
PRM-151 2 milligrams (mg) (0.1 mL volume) by subconjunctival injection Days 1 (immediately following trabeculectomy), 2, 3, 5 and 9
DRUGPlacebo
Placebo solution (0.1 mL volume) by subconjunctival injection Days 1 (immediately following trabeculectomy), 2, 3, 5 and 9
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of Subconjunctival Injection | AEs, slit-lamp, and fundoscopy findings from first injection through end of study; TEAEs from first injection through Day 30 | 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 |
| Subjects With Safety Related Events or Findings | First injection through end of study for AEs, SAEs, visual acuity and visual fields, and from first injection through Day 30 for TEAEs | The number of Subjects with AEs, TEAEs, SAEs, decreased visual acuity, and worsened visual fields |
Other
| Measure | Time frame | Description |
|---|---|---|
| Successful Intra-ocular Pressure (IOP) Control | Day 120 | Exploratory efficacy outcome measure. Successful IOP control defined as IOP between 6 and 18 mm Hg or 25% reduction from pre-surgical IOP |
| Bleb Scarring | Day 120 | 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. |
Countries
Belgium, Czechia, Netherlands, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PRM-151 PRM-151 (recombinant human serum amyloid P, recombinant human pentraxin 2)
PRM-151: PRM-151 2 milligrams (mg) (0.1 mL volume) by subconjunctival injection Days 1 (immediately following trabeculectomy), 2, 3, 5 and 9 | 62 |
| Placebo Placebo
Placebo: Placebo solution (0.1 mL volume) by subconjunctival injection Days 1 (immediately following trabeculectomy), 2, 3, 5 and 9 | 62 |
| Total | 124 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Study Completion | Physician Decision | 1 | 0 |
| Study Completion | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | PRM-151 | Total |
|---|---|---|---|
| Age, Continuous | 68 years | 65 years | 66 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 61 Participants | 59 Participants | 120 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 59 Participants | 58 Participants | 117 Participants |
| Region of Enrollment Belgium | 9 participants | 5 participants | 14 participants |
| Region of Enrollment Czech Republic | 39 participants | 34 participants | 73 participants |
| Region of Enrollment Netherlands | 3 participants | 4 participants | 7 participants |
| Region of Enrollment United Kingdom | 11 participants | 19 participants | 30 participants |
| Sex: Female, Male Female | 32 Participants | 22 Participants | 54 Participants |
| Sex: Female, Male Male | 30 Participants | 40 Participants | 70 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 44 / 62 | 41 / 62 |
| serious Total, serious adverse events | 9 / 62 | 6 / 62 |
Outcome results
Primary
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
Time frame: AEs, slit-lamp, and fundoscopy findings from first injection through end of study; TEAEs from first injection through Day 30
Population: All subjects enrolled in study; all subjects received all study treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PRM-151 | Safety of Subconjunctival Injection | Number of AEs | 274 Number of occurrences |
| PRM-151 | Safety of Subconjunctival Injection | Number of TEAEs | 166 Number of occurrences |
| PRM-151 | Safety of Subconjunctival Injection | Number of Non-ocular TEAEs | 16 Number of occurrences |
| PRM-151 | Safety of Subconjunctival Injection | Number of Ocular TEAEs | 150 Number of occurrences |
| PRM-151 | Safety of Subconjunctival Injection | Number of SAEs | 16 Number of occurrences |
| PRM-151 | Safety of Subconjunctival Injection | Number of abnormal slit-lamp findings | 58 Number of occurrences |
| PRM-151 | Safety of Subconjunctival Injection | Number of abnormal optic nerve findings | 284 Number of occurrences |
| PRM-151 | Safety of Subconjunctival Injection | Number of abnormal retina findings | 18 Number of occurrences |
| PRM-151 | Safety of Subconjunctival Injection | Number of abnormal macula findings | 2 Number of occurrences |
| PRM-151 | Safety of Subconjunctival Injection | Number of abnormal choroid findings | 0 Number of occurrences |
| Placebo | Safety of Subconjunctival Injection | Number of abnormal retina findings | 39 Number of occurrences |
| Placebo | Safety of Subconjunctival Injection | Number of AEs | 220 Number of occurrences |
| Placebo | Safety of Subconjunctival Injection | Number of abnormal slit-lamp findings | 108 Number of occurrences |
| Placebo | Safety of Subconjunctival Injection | Number of TEAEs | 113 Number of occurrences |
| Placebo | Safety of Subconjunctival Injection | Number of abnormal choroid findings | 1 Number of occurrences |
| Placebo | Safety of Subconjunctival Injection | Number of Non-ocular TEAEs | 11 Number of occurrences |
| Placebo | Safety of Subconjunctival Injection | Number of abnormal optic nerve findings | 290 Number of occurrences |
| Placebo | Safety of Subconjunctival Injection | Number of Ocular TEAEs | 102 Number of occurrences |
| Placebo | Safety of Subconjunctival Injection | Number of abnormal macula findings | 4 Number of occurrences |
| Placebo | Safety of Subconjunctival Injection | Number of SAEs | 7 Number of occurrences |
Primary
Subjects With Safety Related Events or Findings
The number of Subjects with AEs, TEAEs, SAEs, decreased visual acuity, and worsened visual fields
Time frame: First injection through end of study for AEs, SAEs, visual acuity and visual fields, and from first injection through Day 30 for TEAEs
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PRM-151 | Subjects With Safety Related Events or Findings | Subjects with at least 1 Treatment Emergent AE | 44 participants |
| PRM-151 | Subjects With Safety Related Events or Findings | Subjects with decreased visual acuity | 0 participants |
| PRM-151 | Subjects With Safety Related Events or Findings | Subjects with at least 1 SAE | 9 participants |
| PRM-151 | Subjects With Safety Related Events or Findings | Subjects with worsened visual field | 5 participants |
| PRM-151 | Subjects With Safety Related Events or Findings | Subjects with at least 1 AE | 46 participants |
| Placebo | Subjects With Safety Related Events or Findings | Subjects with worsened visual field | 5 participants |
| Placebo | Subjects With Safety Related Events or Findings | Subjects with at least 1 AE | 47 participants |
| Placebo | Subjects With Safety Related Events or Findings | Subjects with at least 1 Treatment Emergent AE | 41 participants |
| Placebo | Subjects With Safety Related Events or Findings | Subjects with at least 1 SAE | 6 participants |
| Placebo | Subjects With Safety Related Events or Findings | Subjects with decreased visual acuity | 0 participants |
Other Pre-specified
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.
Time frame: Day 120
Population: Number of subjects who had assessment of bleb scarring on Day 120
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PRM-151 | Bleb Scarring | 1.29 units on a scale | Standard Deviation 0.663 |
| Placebo | Bleb Scarring | 1.30 units on a scale | Standard Deviation 0.633 |
Other Pre-specified
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
Time frame: Day 120
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PRM-151 | Successful Intra-ocular Pressure (IOP) Control | 36 participants |
| Placebo | Successful Intra-ocular Pressure (IOP) Control | 46 participants |