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

Diabetic Retinopathy Clinical Trial

— MATISSE  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01445899
• Other study ID #: QRK202
• Secondary ID: 2011-004157-66
• Status: Completed
• Phase: Phase 2
• First received: September 30, 2011
• Last updated: February 3, 2015
• Start date: February 2012
• Est. completion date: November 2013

Study information

• Verified date: February 2015
• Source: Quark Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationIsrael: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 258
• Est. completion date: November 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Key Stratum I 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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Choroidal Neovascularization
• Diabetic Macular Edema
• Diabetic Retinopathy
• Edema
• Macular Edema
• Neovascularization, Pathologic

Intervention

Drug:
• PF-04523655 (Stratum I)
PF-04523655 (a small interfering RNA) - a single IVT injection
• ranibizumab
6 monthly IVT injections of ranibizumab (Stratum II)
• PF-04523655 (Stratum II)
6 monthly IVT injections of PF-04523655 (a small interfering RNA)

Locations

Country	Name	City	State
Belgium	University Hospital Ghent	Gent
Belgium	Brugmann Ziekenhuis	Laken
Czech Republic	Fakultni nemocnice Brno	Brno
Czech Republic	Fakultní nemocnice Hradec Kralove	Kralove
Czech Republic	Fakultní nemocnice Ostrava	Ostrava
Czech Republic	GEMINI ocní centrum, a.s	Zlín
Germany	Augenärzte Gemeinschaftspraxis Ahaus-Gronau-Lingen-Münster-Bad Bentheim	Ahaus
Germany	Augenklinik Klinikum Darmstadt	Darmstadt
Germany	Klinikum der Stadt Ludwigshafen	Ludwigshafen
Germany	Augenklinik am St. Franziskus-Hospital Muenster	Muenster
Germany	Klinik und Poliklinik für Augenheilkunde Klinikum rechts der Isar	München
Israel	Soroka University Medical Center	Beer Sheva
Israel	Bnai Zion Medical Center	Haifa
Israel	Hadassah Ein Kerem Medical Center	Jerusalem
Israel	Meir Medical Center	Kfar Saba
Israel	Rabin Medical Center	Petah Tiqva
Israel	Kaplan Medical Center	Rehovot
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Israel	The Chaim Sheba Medical Center	Tel-Hashomer
Israel	Assaf Harofe Medical Center	Zerifin
Poland	Oftalmika	Bydgoszcz
Poland	Szpital Specjalistyczny Nr 1 w Bytomiu	Bytom
Poland	Profesorskie Centrum Okulistyki, Hipermarket Tesco	Gdansk
Poland	Spectrum OOK	Wroclaw
United Kingdom	Eye and Ear Clinicl, The Royal Victoria Hospital	Belfast
United Kingdom	Bristol Eye Hospital	Bristol
United Kingdom	Frimley Park Hospital NHS Foundation Trust	Frimley	Surrey
United Kingdom	St. James University Hospital	Leeds
United Kingdom	Moorfields Eye Hospital	London
United Kingdom	Royal Hallamshire Hospital, Eye Department	Sheffield
United Kingdom	Southamptom Eye Unit, Southampton Hospital	Shirley	Southampton
United States	Retina Institute of California	Arcadia	California
United States	Southeast Retina Center	Augusta	Georgia
United States	Retina Research Center	Austin	Texas
United States	Retina-Vitreous Associates	Beverly Hills	California
United States	Retina Diagnostic Center	Campbell	California
United States	Southeast Clinical Research Associates, LLC	Charlotte	North Carolina
United States	Retinal Consultants of Houston	Houston	Texas
United States	Thomas A. Cuilla, MD, PC at Midwest Eye Institute	Indianapolis	Indiana
United States	Valley Retina Institute	McAllen	Texas
United States	MedEye Associates	Miami	Florida
United States	Tennessee Retina, PC	Nashville	Tennessee
United States	Retina Consultants of Arizona	Phoenix	Arizona
United States	Eyesight Ophthalmic Services, PA	Portsmouth	New Hampshire
United States	Black Hills Regioinal Eye Institute	Rapid City	South Dakota
United States	Retinal Institute of Virginia	Richmond	Virginia
United States	Retinal Consultants Medical Group, Inc.	Sacramento	California
United States	Retinal Consultants of San Antonio	San Antonio	Texas
United States	Orange County Reina Medical Group	Santa Ana	California
United States	Retina Vitreous Center	Toms River	New Jersey
United States	Center for Retina and Macular Disease	Winter Haven	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Quark Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  Czech Republic,  Germany,  Israel,  Poland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and dose-limiting toxicities (Stratum I)	- To determine the safety and dose-limiting toxicities of a single intravitreal (IVT) injection of PF-04523655 in subjects with low vision	6 months post-injection	No
Primary	Pharmacokinetics (Stratum I)	- To determine the pharmacokinetics (PK) of a single IVT injection of PF-04523655 in subjects with low vision	6 months post-injection	No
Primary	Safety and tolerability (Stratum II)	- To evaluate the safety and tolerability of PF-04523655 alone and in combination with ranibizumab in subjects with diabetic macular edema (DME)	30 days after the last injection	No
Primary	Efficacy (Stratum II)	- 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	30 days after the last injection	No
Secondary	Anatomical changes in retina and retinal nerve fiber layer morphology (Stratum II)	- 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)	30 days after the last injection	No