Clinical trial NCT01965106: Phase IIA Double-Masked Randomized Sham-Controlled Trial of QPI-1007 Delivered by a Single Intravitreal Injection to Subjects With Acute Primary Angle-Closure Glaucoma (APACG)
Official title: Phase IIA Double-Masked Randomized Sham-Controlled Trial of QPI-1007 Delivered by a Single Intravitreal Injection to Subjects With Acute Primary Angle-Closure Glaucoma (APACG)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Glaucoma, Angle-closure, Primary, Acute
Keywords: Glaucoma, Angle-Closure
Glaucoma, Closed-Angle
Primary angle closure
Acute angle closure
Acute angle-closure glaucoma
Lead sponsor: Quark Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2013-10-18
Enrollment: 46
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: This study will assess any side effects that may occur when QPI-1007 is injected into the eye in subjects with acute primary angle-closure glaucoma, as well as how long it takes for the body to clear the drug. This study will also test whether QPI-1007, injected into the eye, helps prevent both structural damage of the nerve tissue in the eye and the loss of visual function in subjects with acute primary angle-closure glaucoma.

Detailed description: This is a Phase IIa double-masked, single dose, randomized, sham-controlled study evaluating the safety and tolerability, and pharmacokinetics of QPI-1007 versus Control (sham procedure) in subjects with an acute attack of primary angle-closure glaucoma.

Subjects will be randomized at a ratio of 1:1 into one of two study arms: 1.5 QPI-1007 arm or Control arm (sham procedure). The study will enroll approximately 30 subjects into each arm. Randomization will be stratified by time from symptom onset to the study drug administration or sham procedure (≤72 hours and \>72 hours).

Eligibility criteria: Inclusion Criteria:

* Males and females aged at least 40 years or older.
* Onset of symptoms of an acute attack of primary angle-closure in the study eye within the 120 hours prior to the planned study drug administration.
* Best-corrected visual acuity (BCVA) 20/40 or better in the study eye after resolution of the acute attack.
* Received successful treatment for the acute attack of angle-closure, and have undergone laser iridotomy with intraocular pressure in the study eye \<25mm Hg.
* Sufficiently clear ocular media and adequate pupil dilation to allow the optic nerve and fovea to be visualized and assessed in the study eye.
* Female subjects must be: (1) post menopausal, (2) surgically sterile, or (3) using an effective means of contraception.

Exclusion Criteria:

* Previously diagnosed with glaucoma in either eye.
* The time planned for study drug administration is more than 120 hours from the onset of the symptoms.
* History of chronic angle-closure in either eye.
* Secondary angle-closure/secondary angle-closure glaucoma in the study eye.
* Monocular subjects.
* Prior incisional intraocular surgery.
* Inability to perform a reliable visual field test on Day 0 in the study eye.
* History of panretinal photocoagulation or macular laser photocoagulation in the study eye.
* History of active malignancy within the last 5 years (however, non facial, basal cell carcinoma is allowed).
* History of myocardial infarction within the last 6 months.
* Received any drugs known to cause optic nerve or retinal toxicity within 14 days prior to dosing.
* Women who are pregnant or lactating.
* Participating in a concurrent interventional study with the last intervention occurring within 30 days prior to planned dosing with QPI-1007.

Primary outcomes:
measure: Safety and tolerability of a single intravitreal (IVT) dose of QPI-1007 as assessed by adverse events (AE)
timeFrame: Day 0 (after injection) through Month 4. Systemic serious AEs (SAEs) assessed as related to study drug and all ocular SAEs Month 4 to Month 6 after injection
measure: Safety and tolerability of a single IVT dose of QPI-1007 as assessed by laboratory evaluations
timeFrame: Screening, Day 1, and Month 4 after injection
measure: Safety and tolerability of a single IVT dose of QPI-1007 as assessed by vital signs and weight
timeFrame: Weight: Screening and Month 4; Vital signs: Screening, Days 0 (before injection), 1 and 7, and Month 4 to 6
measure: Safety and tolerability of a single IVT dose of QPI-1007 as assessed by ophthalmic evaluations, Best Corrected Visual Acuity (BCVA) using Early Treatment Diabetic Retinopathy Study (EDTRS) chart and slit lamp exams (anterior & posterior segment)
timeFrame: Screening, Days 0, 1 and 7, and Month 1 to 6
measure: Safety and tolerability of a single IVT dose of QPI-1007 as assessed by ophthalmic evaluations, Visual Field (VF) and Spectral Domain Optical Coherence Tomography (SD-OCT)
timeFrame: Days 0 and 7, and Month 1 to 6
measure: Safety and tolerability of a single IVT dose of QPI-1007 as assessed by ophthalmic evaluation intraocular pressure (IOP)
timeFrame: Screening, Days 0 (before injection, both eyes; after injection study eye only), 1 and 7, and Month 1 to 6
measure: Safety and tolerability of a single IVT dose of QPI-1007 as assessed by ophthalmic evaluation, Fundus Photographs (FP)
timeFrame: Days 0 and 7, and Month 4
measure: Safety and tolerability of a single IVT dose of QPI-1007 as assessed by ophthalmic evaluations optic nerve head stereo photographs and contrast sensitivity
timeFrame: Days 0 and 7, and Month 4 and 6
measure: Safety and tolerability of a single IVT dose of QPI-1007 as assessed by use of concomitant treatments
timeFrame: Days 0, 1 and 7, and Month 1 to 6
Secondary outcomes:
measure: QPI-1007 pharmacokinetics (PK) parameters as assessed by the peak plasma concentration (Cmax)
timeFrame: Pre-injection, 1, 4 and 24 hours after injection, and 7 days after injection
measure: QPI-1007 pharmacokinetics (PK) parameters as assessed by the time to peak plasma concentration (Tmax)
timeFrame: Pre-injection, 1, 4 and 24 hours after injection, and 7 days after injection
measure: Difference between QPI-1007 and control group (sham) as assessed by the prevalence of the abnormal visual fields
timeFrame: 4 months after injection
measure: Difference between QPI-1007 and control group (sham) as assessed by change in the mean deviation compared to baseline
timeFrame: 4 months after injection
measure: Difference between QPI-1007 and control group (sham) as assessed by progression of the visual fields compared to baseline
timeFrame: 4 months after injection
measure: Difference between QPI-1007 and control group (sham) as assessed by change in the mean BCVA using the EDTRS chart compared to baseline
timeFrame: 4 months after injection
measure: Difference between QPI-1007 and control group (sham) as assessed by SD-OCT parameters
timeFrame: 4 months after injection
measure: Difference between QPI-1007 and control group (sham) as assessed by change in the mean contrast sensitivity compared to baseline
timeFrame: 4 months after injection
Other outcomes:
Locations:
city: Orange
country: United States
facility: The Gavin Herbert Eye Institute, UC Irvine
state: California
city: Pasadena
country: United States
facility: Doheny Eye Center, UCLA
state: California
city: Houston
country: United States
facility: Robert Cizik Eye Clinic - Clinical Trials Unit
state: Texas
city: Seattle
country: United States
facility: Dept. of Ophthalmology, University of Washington Medical Center
state: Washington
city: Singapore
country: Singapore
facility: Singapore National Eye Centre
city: Ha Noi
country: Vietnam
facility: Hanoi Eye Hospital
city: Ha Noi
country: Vietnam
facility: Vietnam National Institute of Ophthalmology
city: Ho Chi Minh City
country: Vietnam
facility: Ho Chi Minh City Eye Hospital
Study officials:
affiliation: Quark Pharmaceuticals
name: Avner Ingerman, M.D., MSc.
role: STUDY_CHAIR
References: