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

Tracking Information
First Submitted Date ICMJE	September 30, 2011
First Posted Date ICMJE	October 4, 2011
Last Update Posted Date	February 23, 2015
Study Start Date ICMJE	February 2012
Actual Primary Completion Date	November 2013 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: October 3, 2011)	Safety and dose-limiting toxicities (Stratum I) [ Time Frame: 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) [ Time Frame: 6 months post-injection ]- To determine the pharmacokinetics (PK) of a single IVT injection of PF-04523655 in subjects with low vision; Safety and tolerability (Stratum II) [ Time Frame: 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); Efficacy (Stratum II) [ Time Frame: 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
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01445899 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: October 3, 2011)	Anatomical changes in retina and retinal nerve fiber layer morphology (Stratum II) [ Time Frame: 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)
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	PF-04523655 Dose Escalation Study, and Evaluation of PF-04523655 With/Without Ranibizumab in Diabetic Macular Edema (DME)
Official Title ICMJE	An Open-Label Dose Escalation Study of PF-04523655 (Stratum I) Combined With a Prospective, Randomized, Double-Masked, Multi-Center, Controlled Study (Stratum II) Evaluating the Efficacy and Safety of PF-04523655 Alone and in Combination With Ranibizumab Versus Ranibizumab Alone in Diabetic Macular Edema (MATISSE STUDY)
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.; 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.; Stratum II will enroll approximately 240 subjects with DME 1:1:1:1 in up to 4 cohorts of 60 evaluable subjects.
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
Condition ICMJE	Choroidal Neovascularization; Diabetic Retinopathy; Diabetic Macular Edema
Intervention ICMJE	Drug: PF-04523655 (Stratum I) PF-04523655 (a small interfering RNA) - a single IVT injection Other Name: PF-655; Drug: ranibizumab 6 monthly IVT injections of ranibizumab (Stratum II) Other Name: Lucentis; Drug: PF-04523655 (Stratum II) 6 monthly IVT injections of PF-04523655 (a small interfering RNA) Other Name: PF-655
Study Arms	Experimental: PF-04523655 (Stratum II) Stratum II, 6 monthly injections of PF-04523655 only Intervention: Drug: PF-04523655 (Stratum II); Experimental: PF-04523655 and ranibizumab Stratum II, 6 monthly injections of PF-0423655 and ranibizumab administered in combination Interventions: Drug: ranibizumab Drug: PF-04523655 (Stratum II); Active Comparator: ranibizumab Stratum II, 6 monthly IVT injections of ranibizumab only Intervention: Drug: ranibizumab; Experimental: PF-04523655 (Stratum I) Stratum I Intervention: Drug: PF-04523655 (Stratum I)
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: March 28, 2014)	258
Original Estimated Enrollment ICMJE; (submitted: October 3, 2011)	264
Actual Study Completion Date	November 2013
Actual Primary Completion Date	November 2013 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Key Stratum I Inclusion Criteria: Visual acuity in the study eye ≤ 20/200.; Low visual acuity is the result of an irreversible condition affecting the posterior segment of the study eye. Key Stratum I Exclusion Criteria: History of vitrectomy.; History of IVT injection in study eye within last 6 months.; History of vitreous hemorrhage, retinal detachment, or invasive trauma in study eye.; History of uveitis or endophthalmitis in either eye.; Any active inflammatory condition in study eye.; Received any drugs known to cause optic nerve or retinal toxicity within 14 days prior to dosing.; 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.; Intraocular pressure in either eye ≥25 mmHg on maximal medication.; Cataract surgery and laser corneal surgery within 3 months prior to dosing in the study eye and all other intraocular surgeries at any time.; Participation in a concurrent interventional study within 30 days prior to dosing. Key Stratum II Inclusion Criteria: History of diabetes mellitus (Type 1 or Type 2).; Retinal thickening secondary to the edema caused by diabetes mellitus.; Best corrected visual acuity (BCVA) of 20/40 or worse and up to 20/320 or better in the study eye at Screening.; 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: History of panretinal photocoagulation within 6 months or macular laser photocoagulation within 3 months of prior to dosing in the study eye.; Any IVT injection therapy performed in the study eye within 3 months prior to dosing.; 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.; History of vitreoretinal surgery or incisional glaucoma surgery in the study eye.; Prior intraocular surgery or corneal laser surgery, performed within 3 months prior to dosing in the study eye.; Received any drugs known to cause optic nerve or retinal toxicity within 14 days prior to dosing.; High risk (in the opinion of the Investigator) proliferative diabetic retinopathy (PDR) in the study eye.; Current infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye.; Monocular subjects.; History of idiopathic or autoimmune uveitis in either eye.; Aphakia or absence of the posterior capsule in the study eye.; 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.; Uncontrolled glaucoma in either eye.; Spherical equivalent of the refractive error in the study eye of more than -8 diopters myopia.; Use of corticosteroids that, in the Investigator's opinion, may change the status of the subject's diabetic retinopathy in the study eye.
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Belgium, Czech Republic, Germany, Israel, Poland, United Kingdom, United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01445899
Other Study ID Numbers ICMJE	QRK202; 2011-004157-66 ( EudraCT Number )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Quark Pharmaceuticals
Study Sponsor ICMJE	Quark Pharmaceuticals
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: Rabia Ozden, MD Quark Pharmaceuticals
PRS Account	Quark Pharmaceuticals
Verification Date	February 2015
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP