PF-04523655 Dose Escalation Study, and Evaluation of PF-04523655 With/Without Ranibizumab in Diabetic Macular Edema (DME)

NCT ID: NCT01445899

Last Updated: 2015-02-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

258 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-02-29

Study Completion Date

2013-11-30

Brief Summary

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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

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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.

Conditions

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Choroidal Neovascularization Diabetic Retinopathy Diabetic Macular Edema

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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PF-04523655 (Stratum II)

Stratum II, 6 monthly injections of PF-04523655 only

Group Type EXPERIMENTAL

PF-04523655 (Stratum II)

Intervention Type DRUG

6 monthly IVT injections of PF-04523655 (a small interfering RNA)

PF-04523655 and ranibizumab

Stratum II, 6 monthly injections of PF-0423655 and ranibizumab administered in combination

Group Type EXPERIMENTAL

ranibizumab

Intervention Type DRUG

6 monthly IVT injections of ranibizumab (Stratum II)

PF-04523655 (Stratum II)

Intervention Type DRUG

6 monthly IVT injections of PF-04523655 (a small interfering RNA)

ranibizumab

Stratum II, 6 monthly IVT injections of ranibizumab only

Group Type ACTIVE_COMPARATOR

ranibizumab

Intervention Type DRUG

6 monthly IVT injections of ranibizumab (Stratum II)

PF-04523655 (Stratum I)

Stratum I

Group Type EXPERIMENTAL

PF-04523655 (Stratum I)

Intervention Type DRUG

PF-04523655 (a small interfering RNA) - a single IVT injection

Interventions

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PF-04523655 (Stratum I)

PF-04523655 (a small interfering RNA) - a single IVT injection

Intervention Type DRUG

ranibizumab

6 monthly IVT injections of ranibizumab (Stratum II)

Intervention Type DRUG

PF-04523655 (Stratum II)

6 monthly IVT injections of PF-04523655 (a small interfering RNA)

Intervention Type DRUG

Other Intervention Names

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PF-655 Lucentis PF-655

Eligibility Criteria

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Inclusion Criteria

1. Visual acuity in the study eye ≤ 20/200.
2. Low visual acuity is the result of an irreversible condition affecting the posterior segment of the study eye.


1. History of diabetes mellitus (Type 1 or Type 2).
2. Retinal thickening secondary to the edema caused by diabetes mellitus.
3. Best corrected visual acuity (BCVA) of 20/40 or worse and up to 20/320 or better in the study eye at Screening.
4. 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).

Exclusion Criteria

1. History of vitrectomy.
2. History of IVT injection in study eye within last 6 months.
3. History of vitreous hemorrhage, retinal detachment, or invasive trauma in study eye.
4. History of uveitis or endophthalmitis in either eye.
5. Any active inflammatory condition in study eye.
6. Received any drugs known to cause optic nerve or retinal toxicity within 14 days prior to dosing.
7. 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.
8. Intraocular pressure in either eye ≥25 mmHg on maximal medication.
9. Cataract surgery and laser corneal surgery within 3 months prior to dosing in the study eye and all other intraocular surgeries at any time.
10. Participation in a concurrent interventional study within 30 days prior to dosing.


1. History of panretinal photocoagulation within 6 months or macular laser photocoagulation within 3 months of prior to dosing in the study eye.
2. Any IVT injection therapy performed in the study eye within 3 months prior to dosing.
3. 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.
4. History of vitreoretinal surgery or incisional glaucoma surgery in the study eye.
5. Prior intraocular surgery or corneal laser surgery, performed within 3 months prior to dosing in the study eye.
6. Received any drugs known to cause optic nerve or retinal toxicity within 14 days prior to dosing.
7. High risk (in the opinion of the Investigator) proliferative diabetic retinopathy (PDR) in the study eye.
8. Current infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye.
9. Monocular subjects.
10. History of idiopathic or autoimmune uveitis in either eye.
11. Aphakia or absence of the posterior capsule in the study eye.
12. 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.
13. Uncontrolled glaucoma in either eye.
14. Spherical equivalent of the refractive error in the study eye of more than -8 diopters myopia.
15. Use of corticosteroids that, in the Investigator's opinion, may change the status of the subject's diabetic retinopathy in the study eye.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Quark Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Rabia Ozden, MD

Role: STUDY_DIRECTOR

Quark Pharmaceuticals

Locations

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Retina Consultants of Arizona

Phoenix, Arizona, United States

Site Status

Retina Institute of California

Arcadia, California, United States

Site Status

Retina-Vitreous Associates

Beverly Hills, California, United States

Site Status

Retina Diagnostic Center

Campbell, California, United States

Site Status

Retinal Consultants Medical Group, Inc.

Sacramento, California, United States

Site Status

Orange County Reina Medical Group

Santa Ana, California, United States

Site Status

MedEye Associates

Miami, Florida, United States

Site Status

Center for Retina and Macular Disease

Winter Haven, Florida, United States

Site Status

Southeast Retina Center

Augusta, Georgia, United States

Site Status

Thomas A. Cuilla, MD, PC at Midwest Eye Institute

Indianapolis, Indiana, United States

Site Status

Eyesight Ophthalmic Services, PA

Portsmouth, New Hampshire, United States

Site Status

Retina Vitreous Center

Toms River, New Jersey, United States

Site Status

Southeast Clinical Research Associates, LLC

Charlotte, North Carolina, United States

Site Status

Black Hills Regioinal Eye Institute

Rapid City, South Dakota, United States

Site Status

Tennessee Retina, PC

Nashville, Tennessee, United States

Site Status

Retina Research Center

Austin, Texas, United States

Site Status

Retinal Consultants of Houston

Houston, Texas, United States

Site Status

Valley Retina Institute

McAllen, Texas, United States

Site Status

Retinal Consultants of San Antonio

San Antonio, Texas, United States

Site Status

Retinal Institute of Virginia

Richmond, Virginia, United States

Site Status

University Hospital Ghent

Ghent, Belgium, Belgium

Site Status

Brugmann Ziekenhuis

Laken, Belgium, Belgium

Site Status

Fakultni nemocnice Brno

Brno, Czech Republic, Czechia

Site Status

Fakultní nemocnice Hradec Kralove

Kralove, Czech Republic, Czechia

Site Status

Fakultní nemocnice Ostrava

Ostrava, Czech Republic, Czechia

Site Status

GEMINI oční centrum, a.s

Zlín, Czech Republic, Czechia

Site Status

Augenärzte Gemeinschaftspraxis Ahaus-Gronau-Lingen-Münster-Bad Bentheim

Ahaus, Germany, Germany

Site Status

Augenklinik Klinikum Darmstadt

Darmstadt, Germany, Germany

Site Status

Klinikum der Stadt Ludwigshafen

Ludwigshafen, Germany, Germany

Site Status

Klinik und Poliklinik für Augenheilkunde Klinikum rechts der Isar

München, Germany, Germany

Site Status

Augenklinik am St. Franziskus-Hospital Muenster

Münster, Germany, Germany

Site Status

Soroka University Medical Center

Beersheba, Israel, Israel

Site Status

Bnai Zion Medical Center

Haifa, Israel, Israel

Site Status

Meir Medical Center

Kfar Saba, Israel, Israel

Site Status

The Chaim Sheba Medical Center

Tel Litwinsky, Israel, Israel

Site Status

Hadassah Ein Kerem Medical Center

Jerusalem, , Israel

Site Status

Rabin Medical Center

Petah Tikva, , Israel

Site Status

Kaplan Medical Center

Rehovot, , Israel

Site Status

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Site Status

Assaf Harofe Medical Center

Ẕerifin, , Israel

Site Status

Oftalmika

Bydgoszcz, Poland, Poland

Site Status

Szpital Specjalistyczny Nr 1 w Bytomiu

Bytom, Poland, Poland

Site Status

Profesorskie Centrum Okulistyki, Hipermarket Tesco

Gdansk, Poland, Poland

Site Status

Spectrum OOK

Wroclaw, Poland, Poland

Site Status

Southamptom Eye Unit, Southampton Hospital

Shirley, Southampton, United Kingdom

Site Status

Frimley Park Hospital NHS Foundation Trust

Frimley, Surrey, United Kingdom

Site Status

Eye and Ear Clinicl, The Royal Victoria Hospital

Belfast, United Kingdom, United Kingdom

Site Status

Bristol Eye Hospital

Bristol, United Kingdom, United Kingdom

Site Status

St. James University Hospital

Leeds, United Kingdom, United Kingdom

Site Status

Moorfields Eye Hospital

London, United Kingdom, United Kingdom

Site Status

Royal Hallamshire Hospital, Eye Department

Sheffield, United Kingdom, United Kingdom

Site Status

Countries

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United States Belgium Czechia Germany Israel Poland United Kingdom

Other Identifiers

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2011-004157-66

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

QRK202

Identifier Type: -

Identifier Source: org_study_id

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