PF-04523655 Dose Escalation Study, and Evaluation of PF-04523655 With/Without Ranibizumab in Diabetic Macular Edema (DME)
- Conditions
- Choroidal NeovascularizationDiabetic RetinopathyDiabetic Macular Edema
- Interventions
- Registration Number
- NCT01445899
- Lead Sponsor
- Quark Pharmaceuticals
- Brief Summary
This is a two-part study. The first part (Stratum I) is an open-label, dose escalation, safety, tolerability and pharmacokinetic study, where active study drug (PF-04523655) will be given to all patients who participate. Stratum I will determine the maximum tolerated dose and any dose-limiting toxicities. The second part (Stratum II) is a prospectively randomized, multi-center, double-masked, dose ranging study evaluating the efficacy and safety of PF-04523655 alone and in combination with ranibizumab versus ranibizumab alone in patients with DME.
- Detailed Description
Patients will be enrolled concurrently according to one of two sets of criteria designated as Stratum I and Stratum II.
1. Stratum I will enroll up to 24 subjects with low vision, inclusive of possible intermediate doses, in up to 4 cohorts of 3-6 evaluable subjects.
2. Stratum II will enroll approximately 240 subjects with DME 1:1:1:1 in up to 4 cohorts of 60 evaluable subjects.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 258
- Visual acuity in the study eye ≤ 20/200.
- Low visual acuity is the result of an irreversible condition affecting the posterior segment of the study eye.
Key Stratum I
- History of vitrectomy.
- History of IVT injection in study eye within last 6 months.
- History of vitreous hemorrhage, retinal detachment, or invasive trauma in study eye.
- History of uveitis or endophthalmitis in either eye.
- Any active inflammatory condition in study eye.
- Received any drugs known to cause optic nerve or retinal toxicity within 14 days prior to dosing.
- Any medical condition, concomitant therapy or previous incisional or laser surgery that, in the opinion of the Investigator, would preclude IVT injection in the study eye.
- Intraocular pressure in either eye ≥25 mmHg on maximal medication.
- Cataract surgery and laser corneal surgery within 3 months prior to dosing in the study eye and all other intraocular surgeries at any time.
- Participation in a concurrent interventional study within 30 days prior to dosing.
Key Stratum II Inclusion Criteria:
- History of diabetes mellitus (Type 1 or Type 2).
- Retinal thickening secondary to the edema caused by diabetes mellitus.
- Best corrected visual acuity (BCVA) of 20/40 or worse and up to 20/320 or better in the study eye at Screening.
- Standard of care treatment for DME can be withheld for at least 90 days after the subject has enrolled in the study (study eye only).
Key Stratum II Exclusion Criteria:
- History of panretinal photocoagulation within 6 months or macular laser photocoagulation within 3 months of prior to dosing in the study eye.
- Any IVT injection therapy performed in the study eye within 3 months prior to dosing.
- Iris neovascularization, vitreous hemorrhage, tractional retinal detachment, vitreomacular traction, clinically significant epiretinal membrane or clinically significant preretinal fibrosis involving the macula in the study eye.
- History of vitreoretinal surgery or incisional glaucoma surgery in the study eye.
- Prior intraocular surgery or corneal laser surgery, performed within 3 months prior to dosing in the study eye.
- Received any drugs known to cause optic nerve or retinal toxicity within 14 days prior to dosing.
- High risk (in the opinion of the Investigator) proliferative diabetic retinopathy (PDR) in the study eye.
- Current infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye.
- Monocular subjects.
- History of idiopathic or autoimmune uveitis in either eye.
- Aphakia or absence of the posterior capsule in the study eye.
- Structural damage to the center of the macula in the study eye likely to preclude improvement in visual acuity following the resolution of macular edema.
- Uncontrolled glaucoma in either eye.
- Spherical equivalent of the refractive error in the study eye of more than -8 diopters myopia.
- Use of corticosteroids that, in the Investigator's opinion, may change the status of the subject's diabetic retinopathy in the study eye.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description PF-04523655 (Stratum II) PF-04523655 (Stratum II) Stratum II, 6 monthly injections of PF-04523655 only PF-04523655 and ranibizumab ranibizumab Stratum II, 6 monthly injections of PF-0423655 and ranibizumab administered in combination PF-04523655 (Stratum I) PF-04523655 (Stratum I) Stratum I PF-04523655 and ranibizumab PF-04523655 (Stratum II) Stratum II, 6 monthly injections of PF-0423655 and ranibizumab administered in combination ranibizumab ranibizumab Stratum II, 6 monthly IVT injections of ranibizumab only
- Primary Outcome Measures
Name Time Method Safety and dose-limiting toxicities (Stratum I) 6 months post-injection - To determine the safety and dose-limiting toxicities of a single intravitreal (IVT) injection of PF-04523655 in subjects with low vision
Pharmacokinetics (Stratum I) 6 months post-injection - To determine the pharmacokinetics (PK) of a single IVT injection of PF-04523655 in subjects with low vision
Efficacy (Stratum II) 30 days after the last injection - To evaluate the ability of PF-04523655 alone and in combination with ranibizumab to improve visual acuity compared to ranibizumab alone in subjects with DME
Safety and tolerability (Stratum II) 30 days after the last injection - To evaluate the safety and tolerability of PF-04523655 alone and in combination with ranibizumab in subjects with diabetic macular edema (DME)
- Secondary Outcome Measures
Name Time Method Anatomical changes in retina and retinal nerve fiber layer morphology (Stratum II) 30 days after the last injection - To evaluate the anatomical changes in retina and retinal nerve fiber layer (RNFL) morphology following administration of PF-04523655 alone and in combination with ranibizumab compared to ranibizumab alone by fundus photography (FP) and spectral domain optical coherence tomography (SD-OCT)
Trial Locations
- Locations (51)
Orange County Reina Medical Group
🇺🇸Santa Ana, California, United States
Brugmann Ziekenhuis
🇧🇪Laken, Belgium
Retina Diagnostic Center
🇺🇸Campbell, California, United States
Retina Institute of California
🇺🇸Arcadia, California, United States
Retina Consultants of Arizona
🇺🇸Phoenix, Arizona, United States
Retina-Vitreous Associates
🇺🇸Beverly Hills, California, United States
Retinal Consultants Medical Group, Inc.
🇺🇸Sacramento, California, United States
Center for Retina and Macular Disease
🇺🇸Winter Haven, Florida, United States
MedEye Associates
🇺🇸Miami, Florida, United States
Thomas A. Cuilla, MD, PC at Midwest Eye Institute
🇺🇸Indianapolis, Indiana, United States
Retina Vitreous Center
🇺🇸Toms River, New Jersey, United States
Eyesight Ophthalmic Services, PA
🇺🇸Portsmouth, New Hampshire, United States
Southeast Clinical Research Associates, LLC
🇺🇸Charlotte, North Carolina, United States
Black Hills Regioinal Eye Institute
🇺🇸Rapid City, South Dakota, United States
Retina Research Center
🇺🇸Austin, Texas, United States
Tennessee Retina, PC
🇺🇸Nashville, Tennessee, United States
Retinal Consultants of Houston
🇺🇸Houston, Texas, United States
Valley Retina Institute
🇺🇸McAllen, Texas, United States
Retinal Consultants of San Antonio
🇺🇸San Antonio, Texas, United States
Retinal Institute of Virginia
🇺🇸Richmond, Virginia, United States
University Hospital Ghent
🇧🇪Gent, Belgium
Fakultni nemocnice Brno
🇨🇿Brno, Czech Republic
Fakultní nemocnice Hradec Kralove
🇨🇿Kralove, Czech Republic
Fakultní nemocnice Ostrava
🇨🇿Ostrava, Czech Republic
GEMINI oční centrum, a.s
🇨🇿Zlín, Czech Republic
Augenklinik Klinikum Darmstadt
🇩🇪Darmstadt, Germany
Augenärzte Gemeinschaftspraxis Ahaus-Gronau-Lingen-Münster-Bad Bentheim
🇩🇪Ahaus, Germany
Klinikum der Stadt Ludwigshafen
🇩🇪Ludwigshafen, Germany
Augenklinik am St. Franziskus-Hospital Muenster
🇩🇪Muenster, Germany
Klinik und Poliklinik für Augenheilkunde Klinikum rechts der Isar
🇩🇪München, Germany
Soroka University Medical Center
🇮🇱Beer Sheva, Israel
Hadassah Ein Kerem Medical Center
🇮🇱Jerusalem, Israel
Bnai Zion Medical Center
🇮🇱Haifa, Israel
Meir Medical Center
🇮🇱Kfar Saba, Israel
Rabin Medical Center
🇮🇱Petah Tiqva, Israel
Kaplan Medical Center
🇮🇱Rehovot, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
The Chaim Sheba Medical Center
🇮🇱Tel-Hashomer, Israel
Assaf Harofe Medical Center
🇮🇱Zerifin, Israel
Oftalmika
🇵🇱Bydgoszcz, Poland
Szpital Specjalistyczny Nr 1 w Bytomiu
🇵🇱Bytom, Poland
Profesorskie Centrum Okulistyki, Hipermarket Tesco
🇵🇱Gdańsk, Poland
Spectrum OOK
🇵🇱Wroclaw, Poland
Southamptom Eye Unit, Southampton Hospital
🇬🇧Shirley, Southampton, United Kingdom
Frimley Park Hospital NHS Foundation Trust
🇬🇧Frimley, Surrey, United Kingdom
Eye and Ear Clinicl, The Royal Victoria Hospital
🇬🇧Belfast, United Kingdom
Bristol Eye Hospital
🇬🇧Bristol, United Kingdom
St. James University Hospital
🇬🇧Leeds, United Kingdom
Moorfields Eye Hospital
🇬🇧London, United Kingdom
Royal Hallamshire Hospital, Eye Department
🇬🇧Sheffield, United Kingdom
Southeast Retina Center
🇺🇸Augusta, Georgia, United States