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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Macular Edema, Diabetic

Intervention / Treatment
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* Drug: Ranibizumab
* Drug: Placebo
* Drug: PF-04634817
* Drug: Masked Sham Therapy


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1<br>Intravitreal 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. | Drug: Ranibizumab<br>* Intravitreal Injection supplied as: 10 mg/mL in a 0.2 mL vial with instructions on preparation and administration of the 0.5 mg (0.05 mL) dose. 6 mg/mL in a single use vial with instructions on preparation and administration of the 0.3 mg (0.05 mL) dose. Adminstered once a month for 12 weeks<br>Drug: Placebo<br>* Oral Placebo is provided in tablet form to match the 50mg dose of PF-04634817. Dose is 4 tablets each day for 12 weeks<br>|
| Experimental: Arm 2<br>Oral PF-04634817 200 mg, once daily plus a masked sham therapy (given monthly). | Drug: PF-04634817<br>* Four 50mg tablets PF-04634817 once a day for 12 weeks.<br>Drug: Masked Sham Therapy<br>* Empty, needle-less syringe is used by the unmasked team once a month.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Letter Change From Baseline at Week 12 in Best Corrected Visual Acuity (BCVA) | 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). | Baseline (Day 0) and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects Gaining 15 ETDRS Letters in BCVA From Baseline at 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). | Baseline (Day 0) and Week 12 | 
| Mean Change From Baseline in Central Subfield Retinal Thickness in the Study Eye at 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. | Baseline (Day 0) and Week 12 | 
| Mean Change From Baseline in The Area of Fluorescein Leakage in the Study Eye at 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. | Baseline (Day 0) and Week 12 | 
| Mean Change From Baseline in Steps of Diabetic Retinopathy Step (ETDRS Severity Scale) in the Study Eye at 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. | Baseline (Day 0) and Week 12 | 
| Plasma Concentration of PF-04634817 up to Week 12 |  | Week 0, Week 4, Week 8, and Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Chemokine Antagonist, Diabetic Macular Edema, Diabetes Mellitus, Macular Edema, Diabetic Retinopathy, Anti-VEGF