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
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|ClinicalTrials.gov Identifier: NCT01994291|
Recruitment Status : Terminated
First Posted : November 25, 2013
Results First Posted : October 17, 2016
Last Update Posted : October 17, 2016
|Condition or disease||Intervention/treatment||Phase|
|Macular Edema, Diabetic||Drug: Ranibizumab Drug: Placebo Drug: PF-04634817 Drug: Masked Sham Therapy||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||199 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|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 Start Date :||November 2013|
|Actual Primary Completion Date :||August 2015|
|Actual Study Completion Date :||August 2015|
Active Comparator: Arm 1
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.
Intravitreal Injection supplied as:
Oral Placebo is provided in tablet form to match the 50mg dose of PF-04634817.
Dose is 4 tablets each day for 12 weeks
Experimental: Arm 2
Oral PF-04634817 200 mg, once daily plus a masked sham therapy (given monthly).
Four 50mg tablets PF-04634817 once a day for 12 weeks.
Drug: Masked Sham Therapy
Empty, needle-less syringe is used by the unmasked team once a month.
- Mean Letter Change From Baseline at Week 12 in Best Corrected Visual Acuity (BCVA) [ Time Frame: 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).
- Proportion of Subjects Gaining 15 ETDRS Letters in BCVA From Baseline at Week 12 [ Time Frame: Baseline (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 12 [ Time Frame: Baseline (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 12 [ Time Frame: Baseline (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 12 [ Time Frame: Baseline (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 12 [ Time Frame: Week 0, Week 4, Week 8, and Week 12 ]
- Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [ Time Frame: Week 0 to Week 16 ]An AE was any untoward medical occurrence without regard to causality in a participant who received study drug. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
- Number of Participants With Potentially Clinically Important Post-Baseline Vital Signs [ Time Frame: Week -5 to Week 16 ]Number of participants who met the categorical summary of post-baseline criteria at any time point, defined as: supine pulse rate <40 beats per minute (bpm) or >120 bpm; supine systolic blood pressure (SBP) ≥30 millimeters of mercury (mmHg) change from baseline in same posture; supine diastolic BP (DBP) ≥20 mmHg change from baseline in same posture; supine SBP <90 mmHg; supine DBP <50 mmHg.
- Number of Participants With Laboratory Abnormalities [ Time Frame: Week -5 to Week 16 ]The following laboratory parameters were analyzed for abnormalities at any time point: hematology (hemoglobin, hematocrit, red blood cell count (RBC), white blood cell count (WBC) with differential, and platelet count); blood chemistry (sodium, potassium, chloride, bicarbonate, blood urea nitrogen (BUN), creatinine, albumin, calcium, total, direct and indirect bilirubin, gamma glutamyltransferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactic dehydrogenase (LDH), alkaline phosphatase, creatine phosphokinase (CPK), uric acid, amylase and lipase); follicle-stimulating hormone (FSH) (Weeks -5 to 0 only, for postmenopausal women who have been amenorrheic for at least 12 consecutive months prior to screening visit).
- Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings [ Time Frame: Week -5 to Week 16 ]ECG parameters included PR interval, QRS interval, and corrected QT interval using Fridericia's formula (QTcF). Criteria for ECG changes meeting potential clinical concern included: PR interval greater than or equal to (>=)300 milliseconds (msec) or >=25% increase when baseline is greater than (>)200 msec and >=50% increase when baseline is less than or equal to (≤)200 msec; QRS interval >=200 msec or >=25% increase when baseline is greater than (>)200 msec and >=50% increase when baseline is less than or equal to (≤)200 msec; QT interval >=500 msec; and QTcF >=450 msec or >=30 msec increase. The number of participants with potentially clinically significant ECG findings at any visit were reported.
- Number of Participants With Changes in the Anterior Segment of the Study Eye at Week 12 [ Time Frame: Week -5 to Week 16 ]The anterior biomicroscopy exam was done undilated in order to assess whether there was any anterior segment inflammation caused either by ranibizumab or PF-04634817.
- Maximum Increase of Intraocular Pressure (IOP) From Baseline in Study Eye [ Time Frame: Week -5 to Week 16 ]IOP was measured using Goldmann applanation tonometry. To maintain consistency, it was recommended that the same examiner ought to measure IOP with the same tonometer at each visit for a given subject. Intraocular pressure ought to be measured in the study eye approximately 30 minutes after intravitreal injection or masked sham therapy (performed by unmasked study team member).
- Number of Participants With Change in Ophthalmoscopy Examination Results in Study Eye After Administration of Ranibizumab or Masked Sham Therapy at Week 8 [ Time Frame: Week -5 to Week 16 ]Ophthalmoscopy ought to be performed after pupillary dilation to examine the vitreous body, optic nerve head, macular and peripheral retina. All findings, including the presence or absence of vitreous inflammation, ought to be documented. All post-dose ophthalmoscopy assessments ought to be made immediately following the administration of ranibizumab or masked sham therapy.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01994291
|Study Director:||Pfizer CT.gov Call Center||Pfizer|