Primary: To assess the effects of PRM-151 compared to placebo on the success of trabeculectomy by reducing post-surgical scarring in glaucoma patients who have undergone primary trabeculectomy, evaluated at day 120.Secondary: To assess the safety…
ID
Source
Brief title
Condition
- Glaucoma and ocular hypertension
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main co-primary endpoints of the study upon which the efficacy conclusions
will be based are the following:
1. Successful IOP control (either qualified or unqualified) at day 120.
Successful IOP control is defined as unqualified when IOP was between 6 and 18
mmHg or a 25% reduction from the pre-surgical IOP without medication and
qualified when IOP-lowering therapies are required to maintain IOP at that
level.
2. Bleb scarring at day 120, as assessed by OCT.
3. Vascularity of the peripheral, non-bleb conjunctiva at day 120 as assessed
by the Moorfields bleb grading scale.
4. Comparison of mean decrease from baseline in IOP at day 120
The primary analysis will be based on the following null hypotheses:
1. There is no difference for the proportion of subjects with successful IOP
control at day 120 between PRM-151 and placebo.
2. There is no difference for the distribution of bleb scarring at day 120
between PRM-151 and placebo.
3. There is no difference for the distribution of vascularity of the
peripheral, non-bleb conjunctiva at day 120 between PRM-151 and placebo.
4. There is no difference for the mean decrease in IOP at day 120 between
PRM-151 and placebo.
The proportions of subjects with successful IOP control at day 120, the
distributions of bleb scarring at day 120 and the distributions of the
vascularity of the peripheral, non-bleb conjunctivas at day 120 will be
compared between PRM-151 and placebo by Fisher's exact test. The mean decrease
in IOP at day 120 will be compared between PRM-151 and placebo by two sample
t-test.
Secondary outcome
Secondary efficacy endpoints include the primary efficacy endpoints assessed at
all other timepoints, percent change from baseline in IOP, trabeculectomy
failure rate, the mean number of IOP-lowering medications taken per subject,
and the other parameters assessed by Moorfields bleb grading system.
The baseline for IOP will be the IOP measured at the time of the decision to
perform the surgery.
Subjects will be randomized within each stratum in a 1:1 ratio to placebo or
PRM-151. The primary analysis will be based on the intent-to-treat (ITT)
analysis set, which will include all randomized, treated subjects who receive
at least one injection of test article. The last-observation-carried-forward
(LOCF) imputation will be implemented for those subjects with missing efficacy
values, who are prematurely discontinued, or have undergone rescue procedures.
Secondary analyses include the analyses for co-primary endpoints at all
timepoints. In addition, a stratified analysis will be performed using a
Cochran-Mantel-Haenszel (CMH) test (age and baseline IOP as stratification
factors) for IOP control, bleb scarring and vascularity of the peripheral,
non-bleb conjunctiva. For the mean decrease in IOP, an Analysis of Covariance
(ANCOVA) model will be used to include the stratification factors age and
baseline IOP as covariates. Bleb scarring and the vascularity of the
peripheral, non-bleb conjunctiva will be also analyzed as continuous variables.
Background summary
SAP (Serum Amyloid P) is a naturally occurring protein that circulates in the
bloodstream and plays a crucial role in regulating wound healing. SAP's role is
to regulate the activity of innate immune cells including monocyte-derived
cells (fibrocytes, macrophages, dendritic cells) and myofibroblasts. The innate
responses to injury can result in excess collagen production and scarring. This
excess collagen production is an unwanted effect at surgical sites or in
response to injury in a solid organ. Studies conducted show that maintaining an
elevated level of SAP in the blood or locally at the site of injury can prevent
production of excess scarring and the progression of fibrosis.
Study objective
Primary: To assess the effects of PRM-151 compared to placebo on the success of
trabeculectomy by reducing post-surgical scarring in glaucoma patients who have
undergone primary trabeculectomy, evaluated at day 120.
Secondary: To assess the safety and tolerability of PRM-151 administered as a
subconjunctival injection in glaucoma patients who have undergone primary
trabeculectomy.
Study design
This is a multicenter, randomized, double-masked, placebo-controlled 120-day
study of PRM-151 administered as a subconjunctival injection to patients
undergoing primary trabeculectomy followed by an investigator-masked, 240- day
extension.
Intervention
Subjects will be randomly assigned to one of two treatment arms:
A: PRM-151 2 mg will be administered as a subconjunctival injection at the end
of surgery on day 1 followed by an additional injection of PRM-151 2 mg
administered as a subconjunctival injection on days 2, 3, 5 and 9 post-surgery.
B: Placebo will be administered as a subconjunctival injection at the end of
surgery on day 1 followed by an additional injection of placebo administered as
a subconjunctival injection on days 2, 3, 5 and 9 post-surgery.
Study burden and risks
Each subject will participate in the study for approximately 1 year.
Participation will include a screening evaluation within 30 days before initial
test article administration on day 1, 1 visit following surgery and 12 follow
up visits during the year post-surgery. Following surgery, patients will be
evaluated on days 2, 3, 5, 9, 14, 21, 30, 60, 90 and 120 for the double-masked
phase, and on days 180 and 360 for the investigator- masked extension.
Time input visits: screening: half a day - 1 day. 1 visit after surgery: 1 - 3
hours and 12 follow up visits until 1 year after surgery 2 - 4 hours.
Total: appr. 7 - 8 days.
Risks:
In a study of healthy volunteers, the following were common side effects:
headache and fatigue. It is unknown whether the subject will experience these
side effects or not. There is a possibility that an allergic reaction to the
medication can occur. This could require prescribtion of additional medications
to treat this condition.
PRM-151 is a protein and the possibility of an allergic drug reaction does
exist. Early signs and symptoms of anaphylaxis can include urticaria, rhinitis,
conjunctivitis, abdominal pain, vomiting and diarrhea.
Subconjunctival injections: The possible side effects and discomforts of
having an injection under the conjunctiva include the possibility of pain or
bruising at the site of the injection; and rarely, infection at the site of the
injection.
Eye examinations: The risks and discomforts of eye examinations are similar to
those of eye examinations the subject may have had in the past. For example,
dilating drops or anesthetic drops may sting when they are first into your
eyes. Dilation of your pupils may cause some temporary glare and blurring of
vision. The drops could cause an allergic reaction, and, if they are
contaminated, they could cause an infection. This problem is rare.
Slit-lamp photography: The camera flash is bright and may cause temporary
discomfort due to aversion for light.
Tonometry (Measuring the pressure inside the eyes): The instrument used to
measure the pressure of the eye, could scratch the outside of your eye.
Visual Field and OCT: There are no risks or side effects assocatied with these
tests.
Blood draw: There is minimal risk from routine blood drawing, but slight pain
or discomfort during this procedure is common. The side effects from blood
drawing procedures may include the following: discomfort, bleeding or bruising
where the needle enters the body, and in rare cases, fainting, scarring, or
infection.
371 Phoenixville Pike
Malvern, PA 19355
US
371 Phoenixville Pike
Malvern, PA 19355
US
Listed location countries
Age
Inclusion criteria
Inclusion Criteria
General
1. Men or women of nonchildbearing potential (WONCBP) aged 18 years and older at screening.
WONCBP may be included if they are either surgically sterile (hysterectomy and/or oophorectomy) or postmenopausal for >=1 year (with follicle stimulating hormone [FSH] >=38 mIU/mL) and must have a negative pregnancy test result at screening. Women who are surgically sterile must provide documentation of the procedure by an operative report or by ultrasound. Sexually active men must agree to use a medically acceptable form of contraception from day 1 to 12 weeks after the last dose of test article.
2. 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.
3. Suitable candidate for trabeculectomy in the study eye which the physician deems as medically necessary.
Exclusion criteria
Exclusion Criteria
Medical History
1. Diagnosis of glaucoma other than chronic angle-closure glaucoma or open-angle glaucoma (ie., uveitic, traumatic or neovascular glaucoma).
2. Any previous ocular surgeries in the study eye involving the upper conjunctiva and sclera.
3. History of laser surgeries in the study eye within 90 days before day 1.
4. Presence or history of any disease that could affect wound healing.
5. Any asymmetric abnormality of the anterior segment which requires additional intervention (surgery or medication).
6. Any abnormality other than glaucoma in the study eye that could affect tonometry.
7. Presence or history of uveitis within 10 years or any other ocular infection or inflammation within 14 days before day 1.
8. Presence or history of any abnormality or disorder that could interfere with the study procedure or prevent the successful completion of the study.
9. Clear corneal phacoemulsification performed within 90 days before day 1.
10. Any significant unstable cardiovascular, hepatic, renal, respiratory, gastrointestinal, endocrine, immunologic, dermatologic, hematologic, neurologic, or psychiatric disease.
11. Any surgical or medical condition that may interfere with the absorption, distribution, metabolism, or excretion of the test article or the assessment of the effect of the test article.
12. History of drug abuse or alcohol abuse within 1 year before screening that may interfere with the subject*s ability to comply with the protocol requirements.
Physical and Laboratory Findings
13. Conjunctival scarring precluding a trabeculectomy.
14. Vitreous in the anterior chamber.
15. Proliferative retinopathy.
16. Abnormality preventing reliable applanation tonometry in each eye.
Allergies and Adverse Drug Reactions
17. History of drug anaphylaxis to any of the test articles used in this study.
Prohibited Treatments
18. Hemodialysis.
19. Use of any anti-scarring ophthalmologic agents within 90 days before day 1.
20. Use of antimetabolites or systemic steroids within 90 days before day 1.
21. Treatment with cancer chemotherapy within 30 days before day 1.
22. Use of any investigational drug within 30 days before day 1.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-017859-98-NL |
| ClinicalTrials.gov | NCT01064817 |
| CCMO | NL31350.091.10 |