Clinical trial NCT01994291: 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
Official title: A Phase 2, Randomized, Double-Masked, Placebo-Controlled, Parallel Group, Multi-Center Study To Compare The Efficacy And Safety Of A Chemokine CCR2/5 Receptor Antagonist (PF-04634817) With That Of Ranibizumab In Adult Subjects With Diabetic Macular Edema
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Macular Edema, Diabetic
Keywords: Chemokine Antagonist
Diabetic Macular Edema
Diabetes
Diabetes Mellitus
Macular Edema
Diabetic Retinopathy
Anti-VEGF
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2013-11-25
Enrollment: 199
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Mean Letter Change From Baseline at Week 12 in Best Corrected Visual Acuity (BCVA)
timeFrame: Baseline (Day 0) and Week 12
Secondary outcomes:
measure: Proportion of Subjects Gaining 15 ETDRS Letters in BCVA From Baseline at Week 12
timeFrame: Baseline (Day 0) and Week 12
measure: Mean Change From Baseline in Central Subfield Retinal Thickness in the Study Eye at Week 12
timeFrame: Baseline (Day 0) and Week 12
measure: Mean Change From Baseline in The Area of Fluorescein Leakage in the Study Eye at Week 12
timeFrame: Baseline (Day 0) and Week 12
measure: Mean Change From Baseline in Steps of Diabetic Retinopathy Step (ETDRS Severity Scale) in the Study Eye at Week 12
timeFrame: Baseline (Day 0) and Week 12
measure: Plasma Concentration of PF-04634817 up to Week 12
timeFrame: Week 0, Week 4, Week 8, and Week 12
Other outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
timeFrame: Week 0 to Week 16
measure: Number of Participants With Potentially Clinically Important Post-Baseline Vital Signs
timeFrame: Week -5 to Week 16
measure: Number of Participants With Laboratory Abnormalities
timeFrame: Week -5 to Week 16
measure: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings
timeFrame: Week -5 to Week 16
measure: Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12
timeFrame: Week -5 to Week 16
measure: Maximum Increase of Intraocular Pressure (IOP) From Baseline in Study Eye
timeFrame: Week -5 to Week 16
measure: Number of Participants With Change in Ophthalmoscopy Examination Results in Study Eye After Administration of Ranibizumab or Masked Sham Therapy at Week 8
timeFrame: Week -5 to Week 16
Locations:
city: Phoenix
country: United States
facility: Retina Research Institute, LLC
state: Arizona
city: Phoenix
country: United States
facility: Retinal Consultants of Arizona
state: Arizona
city: Phoenix
country: United States
facility: Sunny View Medical Center
state: Arizona
city: Phoenix
country: United States
facility: Premier Research Group Limited
state: Arizona
city: Tucson
country: United States
facility: Retina Centers, P.C.
state: Arizona
city: Arcadia
country: United States
facility: Retina Institute of California
state: California
city: Beverly Hills
country: United States
facility: Retina Vitreous Associates Medical Group
state: California
city: Campbell
country: United States
facility: Retinal Diagnostic Center
state: California
city: Laguna Hills
country: United States
facility: Retina Associates of Orange County
state: California
city: Palm Desert
country: United States
facility: Southern California Desert Retina Consultants
state: California
city: Whittier
country: United States
facility: American Institute of Research (Administrative Only)
state: California
city: New London
country: United States
facility: New England Retina Associates
state: Connecticut
city: Miami
country: United States
facility: Bascom Palmer Eye Institute
state: Florida
city: Plantation
country: United States
facility: Fort Lauderdale Eye Institute
state: Florida
city: Winter Haven
country: United States
facility: Center for Retina and Macular Disease
state: Florida
city: Augusta
country: United States
facility: Southeast Retina Center, PC
state: Georgia
city: Indianapolis
country: United States
facility: Midwest Eye Institute
state: Indiana
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Jackson
country: United States
facility: TLC Eyecare & Laser Center
state: Michigan
city: Royal Oak
country: United States
facility: Wm Beaumont Medical Office Building
state: Michigan
city: Charlotte
country: United States
facility: Charlotte Eye Ear Nose and Throat Associates PA
state: North Carolina
city: Cleveland
country: United States
facility: Retina Associates of Cleveland, Inc.
state: Ohio
city: Youngstown
country: United States
facility: Retina Associates of Cleveland
state: Ohio
city: Oklahoma City
country: United States
facility: Dean McGee Eye Institute
state: Oklahoma
city: Oklahoma City
country: United States
facility: University of Oklahoma -OU Physicians
state: Oklahoma
city: Pittsburgh
country: United States
facility: Retina Vitreous Consultants
state: Pennsylvania
city: West Mifflin
country: United States
facility: Associates in Ophthalmology Ltd
state: Pennsylvania
city: Rapid City
country: United States
facility: Black Hills Regional Eye Institute
state: South Dakota
city: Austin
country: United States
facility: Brain B.Berger,MD,PA
state: Texas
city: Austin
country: United States
facility: Retina Research Center
state: Texas
city: Houston
country: United States
facility: Retina Consultants of Houston, PA
state: Texas
city: San Antonio
country: United States
facility: Medical Center Ophthalmology Associates
state: Texas
city: Salt Lake City
country: United States
facility: Rocky Mountain Retina Consultants
state: Utah
city: Sofia
country: Bulgaria
facility: MC Comac Medical
city: Hradec Kralove
country: Czech Republic
facility: Fakultní nemocnice Hradec Králové, Ocni klinika
city: Hradec Kralove
country: Czech Republic
facility: Fakultní nemocnice Hradec Králové, Nemocnicni lekarna
city: Ostrava - Poruba
country: Czech Republic
facility: Fakultni nemocnice Ostrava, lekarna
city: Ostrava - Poruba
country: Czech Republic
facility: Fakultni nemocnice Ostrava, Ocni klinika
city: Praha 10
country: Czech Republic
facility: Fakultni nemocnice Kralovske Vinohrady, Oftalmologicka klinika
city: Praha 10
country: Czech Republic
facility: Fakultni nemocnice Kralovske Vinohrady, Ustavni lekarna
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg
state: Bavaria
city: Berlin
country: Germany
facility: Charite - Universitaetsmedizin Berlin, Campus Benjamin Franklin
city: Goettingen
country: Germany
facility: Universitaetsmedizin Goettingen
city: Mainz
country: Germany
facility: Universitatsmedizin Mainz
city: Muenster
country: Germany
facility: Augenärzte am St. Franziskus-Hospital
city: Muenster
country: Germany
facility: Universitaetsklinikum Muenster
city: Sulzbach, Saar
country: Germany
facility: Knappschaftsklinikum GmbH
city: Tubingen
country: Germany
facility: Universitatsklinikum Tubingen
city: Budapest
country: Hungary
facility: Semmelweis Egyetem, Szemészeti Klinika
city: Budapest
country: Hungary
facility: Bajcsy-Zsilinszky Korhaz, Szemeszet
city: Budapest
country: Hungary
facility: Budapest Retina Associates Kft.
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Orvos- es Egeszsegtudomanyi Centrum, Szemklinika
city: Pecs
country: Hungary
facility: Ganglion Orvosi Kozpont
city: Veszprem
country: Hungary
facility: Csolnoky Ferenc Korhaz, Szemeszeti Osztaly
city: Jerusalem
country: Israel
facility: Hadassah Medical Organization, Hadassah Medical Center, Ein Karem
city: Kfar Saba
country: Israel
facility: Meir Medical Center
city: Petah Tikva
country: Israel
facility: Rabin Medical Center, Beilinson Hospital
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Chisinau
country: Moldova, Republic of
facility: Spitalul Clinic Republican
city: Wroclaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny Im. Jana Mikulicza Radeckiego We Wrocławiu, Klinika Okulistyki
city: Bucuresti
country: Romania
facility: Med Life SA, Sectia Oftalmologie
city: Bucuresti
country: Romania
facility: Institutul National de Diabet, Nutritie si Boli Metabolice "N.C.Paulescu"
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Gale JD, Berger B, Gilbert S, Popa S, Sultan MB, Schachar RA, Girgenti D, Perros-Huguet C. A CCR2/5 Inhibitor, PF-04634817, Is Inferior to Monthly Ranibizumab in the Treatment of Diabetic Macular Edema. Invest Ophthalmol Vis Sci. 2018 May 1;59(6):2659-2669. doi: 10.1167/iovs.17-22731.