Evaluate whether the clinical efficacy of PF-04634817 is non-inferior to ranibizumab, as measured by change from baseline in best corrected visual acuity after 12 weeks of treatment in subjects with diabetic macular edema (DME).
- Conditions
- Diabetic macular edema (DME)MedDRA version: 17.1Level: LLTClassification code 10057934Term: Diabetic macular edemaSystem Organ Class: 100000004853Therapeutic area: Diseases [C] - Eye Diseases [C11]
- Registration Number
- EUCTR2013-003147-27-DE
- Lead Sponsor
- Pfizer Inc 235 East 42nd Street, New York, NY 10017 US
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 200
1. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the study.
2. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
3. Female subjects of non-childbearing potential =18 years and male subjects =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.
4. Clinical diagnosis of diabetes mellitus (type 1 or type 2).
5. Stable medication for the management of diabetes (for those subjects on anti-diabetes medication) for at least 3 months before randomization and expected to remain stable during the study.
6. Serum HbA1c =10.5% at the screening visit.
7. Diabetic macular edema affecting the fovea in the study eye, consisting of central retinal thickness on OCT measuring 250 µm or more at the screening visit and a diagnosis of DME confirmed by fluorescein angiography.
8. Reduced visual acuity resulting from retinal thickening involving the center of the fovea and a BCVA, using ETDRS visual acuity protocol of 20/32 or worse (letter score of =78) and up to 20/320 or better (letter score =24) in the study eye at the screening visit.
9. Visual acuity score in the non-study eye of 20/400 or better (letter score of =19) at the screening visit.
10. Subjects who have not been treated with anti-angiogenic therapy, including pegaptanib sodium, bevacizumab, ranibizumab or aflibercept, or intra/peri-ocular steroids in either
eye within 3 months of the screening visit and who, from a clinical perspective, are considered suitable for the withholding of treatment for diabetic macular edema, including laser photocoagulation, for the duration of the study following enrolment (at least 90 days).
11. Ocular media and adequate pupillary dilation to allow good quality OCT and fundus photography.
12. If both eyes meet the inclusion criteria for this study, the most severely affected eye will become the study eye. If both eyes are affected equally, then the investigator and the
subject will select the study eye.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100
1. Subjects (subs) who are investigational site staff members directly
involved in the conduct of the trial and their family members, site staff members otherwise supervised by the Investigator, or subs who are Pfizer employees directly involved in the conduct of the trial. 2.
Participation in other studies involving investigational drug(s) (Ph. 1-4)
during study participation or within the prev. 60 days or 5 half-lives
preceding the 1st dose of study medication whichever is longer. 3. Other severe acute or chronic med or psychiatric condition or lab abnormality that may incr the risk associated with study participation or investigational product (IP) administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappro. for entry into this study. 4. Females of childbearing potential or who are pregnant or breastfeeding. 5. Males of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 28 days after the last dose of IP. 6. Known history of HIV based on documented history with + serological test, or + HIV serological test at screening. 7. Any history of prev. untreated or current evidence of active or untreated latent infection with Mycobacterium tuberculosis (TB). 8. Family history of prolonged QT syndrome, or who themselves have a QTC >450 ms for males or >470 ms for females, a QRS >120 ms, or PR interval =300 ms, whether considered clinically significant or not, should not be incl. in study. Any clinically-significant ischemic changes as assessed by the investigator by 12-lead ECG at screening. The ECG should be repeated two more times and the av. of 3 QTc, QRS or PR values should be used to determine the subject's eligibility. QT should be corrected using Fridericia's correction. 9. Severely impaired renal function as defined by an eGFR of <30 mL/min/1.73m2 calculated using the CKDEPI eqn. at screening. 10. Any relevant, clinically-significant abnormalities on physical examination or clinically-significant lab tests, including subs with mod. liver function test abnormalities >1.5 times the upper limit of normal. 11. Pan retinal photocoagulation or macular photocoagulation performed in either eye within 3 mo. of the screening visit. 12. Any intraocular condition or prev. surgery in either eye that, in the opinion of the investigator, would either (a) likely require medical or surgical intervention during the 16 wk duration of the study to prevent or treat visual loss that might result
from that condition, or (b) if allowed to progress untreated, would likely contribute to loss of at least 2 ETDRS lines of BCVA over a 16 wk period, or (c) may affect macular edema or reduce visual acuity during the course of the study. 13. Ocular or peri-ocular infection in the study eye. 14. Cataract surgery in either eye within 60 days prior to study enrolment. 15. High risk proliferative diabetic retinopathy (PDR) in either eye. Inactive fibrosed neovascularization following pan retinal photocoagulation (PRP) laser therapy and non high risk PDR with no evidence of vitreous hemorrhage is permitted. 16. Structural damage to the center of the macula in either eye likely to preclude improvement in visual acuity following the resolution of macular edema, including but not limited to persistent DME involving the foveal center of more than 2 yrs in durati
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Timepoint(s) of evaluation of this end point: Visit 2 - visit 5;Main Objective: Evaluate whether the clinical efficacy of PF-04634817 is non-inferior to ranibizumab, as measured by change from baseline in best corrected visual acuity after 12 weeks of treatment in subjects with diabetic macular edema (DME).;Secondary Objective: - To evaluate the safety and tolerability of PF-04634817 following 12 weeks of treatment.<br>- To evaluate the effects of PF-04634817 on macular edema (central retinal thickness and vascular leakage) and retinopathy.<br>- To evaluate the systemic exposure of PF-04634817 in subjects with type 1 or type 2 diabetes and macular edema.;Primary end point(s): Mean letter change from baseline (Day 0) at Week 12 in best corrected visual acuity (BCVA), as measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity protocol (ETDRS-BCVA),12 of PF-04634817 compared to ranibizumab.
- Secondary Outcome Measures
Name Time Method Timepoint(s) of evaluation of this end point: Visit 2 - visit 5;Secondary end point(s): - The proportion of subjects gaining 15 ETDRS letters in BCVA from baseline at Week 12.<br>- Mean changes in central subfield retinal thickness from baseline at Week 12 as assessed by optical coherence tomography (OCT).<br>- Mean changes in the area of fluorescein leakage from baseline by scheduled study visit up to Week 12, as assessed by fluorescein angiography (FA).<br>- Mean change in steps of diabetic retinopathy (ETDRS severity scale) from baseline at Week 12, as assessed by digital fundus photography (FP).<br>- The systemic exposure of PF-04634817 in subjects with diabetes and macular edema.