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A Phase 2, Multi-Center Study To Compare The Efficacy And Safety Of A Chemokine CCR2/5 Receptor Antagonist With Ranibizumab In Adults With Diabetic Macular Edema

Phase 2
Terminated
Conditions
Macular Edema, Diabetic
Interventions
Drug: Masked Sham Therapy
Drug: Placebo
Registration Number
NCT01994291
Lead Sponsor
Pfizer
Brief Summary

The study hypothesis under test is that administration of the CCR2/5 antagonist has the potential to be as effective as the current treatment options for subjects with diabetic macular edema. The current treatment option for these subjects is an injection directly into the eye, while this CCR2/5 antagonist would be an oral drug which has the potential to be just as effective. This CCR2/5 antagonist also has a broader anti-inflammatory potential and might be able to provide an alternative mechanism to treat Diabetic Macular Edema.

Detailed Description

Study recruitment was stopped on April 9, 2015. This decision was taken for business reasons due to changes in the prioritization of the drug development portfolio. This decision was not as a result of any evolving safety, efficacy issue or changes in the risk:benefit assessment of this product or regulatory interactions.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
199
Inclusion Criteria
  • Patients with Diabetes Mellitus (Type 1 or Type 2) Showing Diabetic Macular Edema in the Eye

  • Reduced visual acuity resulting from retinal thickening

  • Female subjects of non-childbearing potential ≥18 years and male subjects greater than or equal to 18 years. A subject is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active.

  • Female subjects who are not of childbearing potential must meet at least one of the following criteria:

    • Have undergone a documented hysterectomy and/or bilateral oophorectomy;
    • Have medically confirmed ovarian failure; or
    • Achieved post-menopausal status, defined as: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and have a serum follicle stimulating hormone (FSH) level within the laboratory's reference range for postmenopausal females.
Exclusion Criteria
  • Severe Impaired Renal Function
  • Any intraocular condition or previous surgery in either eye that would likely require medical or surgical intervention during the study duration or if allowed to progress untreated for the 16 weeks of study duration, would likely contribute to a reduction in visual acuity.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm 1RanibizumabIntravitreal administration of ranibizumab (either 0.3 or 0.5 mg, given monthly, as detailed in the prescribing information and label content approved for the country governing the study site) plus an oral placebo.
Arm 2Masked Sham TherapyOral PF-04634817 200 mg, once daily plus a masked sham therapy (given monthly).
Arm 1PlaceboIntravitreal administration of ranibizumab (either 0.3 or 0.5 mg, given monthly, as detailed in the prescribing information and label content approved for the country governing the study site) plus an oral placebo.
Arm 2PF-04634817Oral PF-04634817 200 mg, once daily plus a masked sham therapy (given monthly).
Primary Outcome Measures
NameTimeMethod
Mean Letter Change From Baseline at Week 12 in Best Corrected Visual Acuity (BCVA)Baseline (Day 0) and Week 12

Refraction and visual acuity were assessed through the BCVA obtained using the retro illuminated early treatment diabetic retinopathy study (ETDRS) charts. Distance visual acuity was expressed as an ETDRS score (number of letters correctly read).

Secondary Outcome Measures
NameTimeMethod
Proportion of Subjects Gaining 15 ETDRS Letters in BCVA From Baseline at Week 12Baseline (Day 0) and Week 12

Refraction and visual acuity were assessed through the BCVA obtained using the retro illuminated ETDRS charts. Distance visual acuity was expressed as an ETDRS score (number of letters correctly read).

Mean Change From Baseline in Central Subfield Retinal Thickness in the Study Eye at Week 12Baseline (Day 0) and Week 12

A central reading center was used for the evaluation. A photographer or technician pre certified ("study certified") by the Central Reading Center ought to perform all optical coherence tomography (OCT) imaging. Use of a Spectralis or Cirrus OCT was acceptable.

Mean Change From Baseline in The Area of Fluorescein Leakage in the Study Eye at Week 12Baseline (Day 0) and Week 12

Fluorescein Angiography (FA) using certified digital systems was taken by a photographer who had been pre-certified ("study-certified") by the Central Reading Center. They were evaluated by the Central Reading Center.

Mean Change From Baseline in Steps of Diabetic Retinopathy Step (ETDRS Severity Scale) in the Study Eye at Week 12Baseline (Day 0) and Week 12

Stereo color fundus photographs using certified digital systems were taken by a photographer who had been pre-certified ("study certified") by the Central Reading Center. They were evaluated by the Central Reading Center.

Plasma Concentration of PF-04634817 up to Week 12Week 0, Week 4, Week 8, and Week 12

Trial Locations

Locations (63)

Retinal Diagnostic Center

🇺🇸

Campbell, California, United States

Southern California Desert Retina Consultants

🇺🇸

Palm Desert, California, United States

American Institute of Research (Administrative Only)

🇺🇸

Whittier, California, United States

New England Retina Associates

🇺🇸

New London, Connecticut, United States

Center for Retina and Macular Disease

🇺🇸

Winter Haven, Florida, United States

Retina Associates of Orange County

🇺🇸

Laguna Hills, California, United States

Fort Lauderdale Eye Institute

🇺🇸

Plantation, Florida, United States

Southeast Retina Center, PC

🇺🇸

Augusta, Georgia, United States

Retina Vitreous Consultants

🇺🇸

Pittsburgh, Pennsylvania, United States

Bascom Palmer Eye Institute

🇺🇸

Miami, Florida, United States

Midwest Eye Institute

🇺🇸

Indianapolis, Indiana, United States

Charlotte Eye Ear Nose and Throat Associates PA

🇺🇸

Charlotte, North Carolina, United States

Dean McGee Eye Institute

🇺🇸

Oklahoma City, Oklahoma, United States

Fakultni nemocnice Ostrava, lekarna

🇨🇿

Ostrava - Poruba, Czech Republic

Bajcsy-Zsilinszky Korhaz, Szemeszet

🇭🇺

Budapest, Hungary

Fakultni nemocnice Kralovske Vinohrady, Oftalmologicka klinika

🇨🇿

Praha 10, Czech Republic

Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum, Szemklinika

🇭🇺

Debrecen, Hungary

Hadassah Medical Organization, Hadassah Medical Center, Ein Karem

🇮🇱

Jerusalem, Israel

Ganglion Orvosi Kozpont

🇭🇺

Pecs, Hungary

Tel Aviv Sourasky Medical Center

🇮🇱

Tel Aviv, Israel

MC Comac Medical

🇧🇬

Sofia, Bulgaria

Fakultni nemocnice Kralovske Vinohrady, Ustavni lekarna

🇨🇿

Praha 10, Czech Republic

Meir Medical Center

🇮🇱

Kfar Saba, Israel

Universitätsklinikum Regensburg

🇩🇪

Regensburg, Bavaria, Germany

Fakultní nemocnice Hradec Králové, Ocni klinika

🇨🇿

Hradec Kralove, Czech Republic

Fakultni nemocnice Ostrava, Ocni klinika

🇨🇿

Ostrava - Poruba, Czech Republic

Spitalul Clinic Republican

🇲🇩

Chisinau, Moldova, Republic of

Uniwersytecki Szpital Kliniczny Im. Jana Mikulicza Radeckiego We Wrocławiu, Klinika Okulistyki

🇵🇱

Wroclaw, Poland

Semmelweis Egyetem, Szemészeti Klinika

🇭🇺

Budapest, Hungary

Fakultní nemocnice Hradec Králové, Nemocnicni lekarna

🇨🇿

Hradec Kralove, Czech Republic

Csolnoky Ferenc Korhaz, Szemeszeti Osztaly

🇭🇺

Veszprem, Hungary

Institutul National de Diabet, Nutritie si Boli Metabolice "N.C.Paulescu"

🇷🇴

Bucuresti, Romania

Premier Research Group Limited

🇺🇸

Phoenix, Arizona, United States

Budapest Retina Associates Kft.

🇭🇺

Budapest, Hungary

Rabin Medical Center, Beilinson Hospital

🇮🇱

Petah Tikva, Israel

Sunny View Medical Center

🇺🇸

Phoenix, Arizona, United States

Retina Centers, P.C.

🇺🇸

Tucson, Arizona, United States

Retina Research Institute, LLC

🇺🇸

Phoenix, Arizona, United States

Retina Institute of California

🇺🇸

Arcadia, California, United States

Retina Associates of Cleveland

🇺🇸

Youngstown, Ohio, United States

Retina Vitreous Associates Medical Group

🇺🇸

Beverly Hills, California, United States

Tufts Medical Center

🇺🇸

Boston, Massachusetts, United States

Retina Associates of Cleveland, Inc.

🇺🇸

Cleveland, Ohio, United States

Brain B.Berger,MD,PA

🇺🇸

Austin, Texas, United States

Wm Beaumont Medical Office Building

🇺🇸

Royal Oak, Michigan, United States

Black Hills Regional Eye Institute

🇺🇸

Rapid City, South Dakota, United States

Medical Center Ophthalmology Associates

🇺🇸

San Antonio, Texas, United States

Rocky Mountain Retina Consultants

🇺🇸

Salt Lake City, Utah, United States

Associates in Ophthalmology Ltd

🇺🇸

West Mifflin, Pennsylvania, United States

Retina Research Center

🇺🇸

Austin, Texas, United States

Retina Consultants of Houston, PA

🇺🇸

Houston, Texas, United States

Universitatsmedizin Mainz

🇩🇪

Mainz, Germany

Charite - Universitaetsmedizin Berlin, Campus Benjamin Franklin

🇩🇪

Berlin, Germany

Knappschaftsklinikum GmbH

🇩🇪

Sulzbach, Saar, Germany

Universitatsklinikum Tubingen

🇩🇪

Tubingen, Germany

Universitaetsklinikum Muenster

🇩🇪

Muenster, Germany

Kaplan Medical Center

🇮🇱

Rehovot, Israel

Med Life SA, Sectia Oftalmologie

🇷🇴

Bucuresti, Romania

Universitaetsmedizin Goettingen

🇩🇪

Goettingen, Germany

Augenärzte am St. Franziskus-Hospital

🇩🇪

Muenster, Germany

Retinal Consultants of Arizona

🇺🇸

Phoenix, Arizona, United States

TLC Eyecare & Laser Center

🇺🇸

Jackson, Michigan, United States

University of Oklahoma -OU Physicians

🇺🇸

Oklahoma City, Oklahoma, United States

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