PF-04523655 Dose Escalation Study, and Evaluation of PF-04523655 With/Without Ranibizumab in Diabetic Macular Edema (DME)

Phase 2

Completed

• Conditions: Choroidal Neovascularization; Diabetic Retinopathy; Diabetic Macular Edema
• Interventions: Drug: PF-04523655 (Stratum II); Drug: ranibizumab; Drug: PF-04523655 (Stratum I)

• Registration Number: NCT01445899
• Lead Sponsor: Quark Pharmaceuticals

Brief Summary

This is a two-part study. The first part (Stratum I) is an open-label, dose escalation, safety, tolerability and pharmacokinetic study, where active study drug (PF-04523655) will be given to all patients who participate. Stratum I will determine the maximum tolerated dose and any dose-limiting toxicities. The second part (Stratum II) is a prospectively randomized, multi-center, double-masked, dose ranging study evaluating the efficacy and safety of PF-04523655 alone and in combination with ranibizumab versus ranibizumab alone in patients with DME.

Detailed Description

Patients will be enrolled concurrently according to one of two sets of criteria designated as Stratum I and Stratum II.

1. Stratum I will enroll up to 24 subjects with low vision, inclusive of possible intermediate doses, in up to 4 cohorts of 3-6 evaluable subjects.

2. Stratum II will enroll approximately 240 subjects with DME 1:1:1:1 in up to 4 cohorts of 60 evaluable subjects.

Study Timeline

• Study First Submitted: 2011-09-30
• Study First Submitted QC: 2011-10-03
• Study First Posted: 2011-10-04
• Study Start: 2012-02
• Primary Completion: 2013-11
• Study Completion: 2013-11
• Disposition First Submitted: 2015-01-16
• Disposition First Submitted QC: 2015-01-16
• Disposition First Posted: 2015-01-29
• Status Verified: 2015-02
• Last Update Submitted: 2015-02-03
• Last Update Posted: 2015-02-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 258

Inclusion Criteria

1. Visual acuity in the study eye ≤ 20/200.
2. Low visual acuity is the result of an irreversible condition affecting the posterior segment of the study eye.

Key Stratum I

Exclusion Criteria

1. History of vitrectomy.
2. History of IVT injection in study eye within last 6 months.
3. History of vitreous hemorrhage, retinal detachment, or invasive trauma in study eye.
4. History of uveitis or endophthalmitis in either eye.
5. Any active inflammatory condition in study eye.
6. Received any drugs known to cause optic nerve or retinal toxicity within 14 days prior to dosing.
7. Any medical condition, concomitant therapy or previous incisional or laser surgery that, in the opinion of the Investigator, would preclude IVT injection in the study eye.
8. Intraocular pressure in either eye ≥25 mmHg on maximal medication.
9. Cataract surgery and laser corneal surgery within 3 months prior to dosing in the study eye and all other intraocular surgeries at any time.
10. Participation in a concurrent interventional study within 30 days prior to dosing.

Key Stratum II Inclusion Criteria:

1. History of diabetes mellitus (Type 1 or Type 2).
2. Retinal thickening secondary to the edema caused by diabetes mellitus.
3. Best corrected visual acuity (BCVA) of 20/40 or worse and up to 20/320 or better in the study eye at Screening.
4. Standard of care treatment for DME can be withheld for at least 90 days after the subject has enrolled in the study (study eye only).

Key Stratum II Exclusion Criteria:

1. History of panretinal photocoagulation within 6 months or macular laser photocoagulation within 3 months of prior to dosing in the study eye.
2. Any IVT injection therapy performed in the study eye within 3 months prior to dosing.
3. Iris neovascularization, vitreous hemorrhage, tractional retinal detachment, vitreomacular traction, clinically significant epiretinal membrane or clinically significant preretinal fibrosis involving the macula in the study eye.
4. History of vitreoretinal surgery or incisional glaucoma surgery in the study eye.
5. Prior intraocular surgery or corneal laser surgery, performed within 3 months prior to dosing in the study eye.
6. Received any drugs known to cause optic nerve or retinal toxicity within 14 days prior to dosing.
7. High risk (in the opinion of the Investigator) proliferative diabetic retinopathy (PDR) in the study eye.
8. Current infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye.
9. Monocular subjects.
10. History of idiopathic or autoimmune uveitis in either eye.
11. Aphakia or absence of the posterior capsule in the study eye.
12. Structural damage to the center of the macula in the study eye likely to preclude improvement in visual acuity following the resolution of macular edema.
13. Uncontrolled glaucoma in either eye.
14. Spherical equivalent of the refractive error in the study eye of more than -8 diopters myopia.
15. Use of corticosteroids that, in the Investigator's opinion, may change the status of the subject's diabetic retinopathy in the study eye.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PF-04523655 (Stratum II)	PF-04523655 (Stratum II)	Stratum II, 6 monthly injections of PF-04523655 only
PF-04523655 and ranibizumab	ranibizumab	Stratum II, 6 monthly injections of PF-0423655 and ranibizumab administered in combination
PF-04523655 (Stratum I)	PF-04523655 (Stratum I)	Stratum I
PF-04523655 and ranibizumab	PF-04523655 (Stratum II)	Stratum II, 6 monthly injections of PF-0423655 and ranibizumab administered in combination
ranibizumab	ranibizumab	Stratum II, 6 monthly IVT injections of ranibizumab only

Primary Outcome Measures

Name	Time	Method
Safety and dose-limiting toxicities (Stratum I)	6 months post-injection	- To determine the safety and dose-limiting toxicities of a single intravitreal (IVT) injection of PF-04523655 in subjects with low vision
Pharmacokinetics (Stratum I)	6 months post-injection	- To determine the pharmacokinetics (PK) of a single IVT injection of PF-04523655 in subjects with low vision
Efficacy (Stratum II)	30 days after the last injection	- To evaluate the ability of PF-04523655 alone and in combination with ranibizumab to improve visual acuity compared to ranibizumab alone in subjects with DME
Safety and tolerability (Stratum II)	30 days after the last injection	- To evaluate the safety and tolerability of PF-04523655 alone and in combination with ranibizumab in subjects with diabetic macular edema (DME)

Secondary Outcome Measures

Name	Time	Method
Anatomical changes in retina and retinal nerve fiber layer morphology (Stratum II)	30 days after the last injection	- To evaluate the anatomical changes in retina and retinal nerve fiber layer (RNFL) morphology following administration of PF-04523655 alone and in combination with ranibizumab compared to ranibizumab alone by fundus photography (FP) and spectral domain optical coherence tomography (SD-OCT)

Trial Locations

Locations (51)

Retina Consultants of Arizona; 🇺🇸 Phoenix, Arizona, United States

Retina Institute of California; 🇺🇸 Arcadia, California, United States

Retina-Vitreous Associates; 🇺🇸 Beverly Hills, California, United States

Retina Diagnostic Center; 🇺🇸 Campbell, California, United States

Retinal Consultants Medical Group, Inc.; 🇺🇸 Sacramento, California, United States

Orange County Reina Medical Group; 🇺🇸 Santa Ana, California, United States

MedEye Associates; 🇺🇸 Miami, Florida, United States

Center for Retina and Macular Disease; 🇺🇸 Winter Haven, Florida, United States

Southeast Retina Center; 🇺🇸 Augusta, Georgia, United States

Thomas A. Cuilla, MD, PC at Midwest Eye Institute; 🇺🇸 Indianapolis, Indiana, United States

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