Clinical trial NCT01445899: PF-04523655 Dose Escalation Study, and Evaluation of PF-04523655 With/Without Ranibizumab in Diabetic Macular Edema (DME)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Choroidal Neovascularization
Diabetic Retinopathy
Diabetic Macular Edema
Lead sponsor: Quark Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2011-10-04
Enrollment: 258
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety and dose-limiting toxicities (Stratum I)
timeFrame: 6 months post-injection
measure: Pharmacokinetics (Stratum I)
timeFrame: 6 months post-injection
measure: Safety and tolerability (Stratum II)
timeFrame: 30 days after the last injection
measure: Efficacy (Stratum II)
timeFrame: 30 days after the last injection
Secondary outcomes:
measure: Anatomical changes in retina and retinal nerve fiber layer morphology (Stratum II)
timeFrame: 30 days after the last injection
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Retina Consultants of Arizona
state: Arizona
city: Arcadia
country: United States
facility: Retina Institute of California
state: California
city: Beverly Hills
country: United States
facility: Retina-Vitreous Associates
state: California
city: Campbell
country: United States
facility: Retina Diagnostic Center
state: California
city: Sacramento
country: United States
facility: Retinal Consultants Medical Group, Inc.
state: California
city: Santa Ana
country: United States
facility: Orange County Reina Medical Group
state: California
city: Miami
country: United States
facility: MedEye Associates
state: Florida
city: Winter Haven
country: United States
facility: Center for Retina and Macular Disease
state: Florida
city: Augusta
country: United States
facility: Southeast Retina Center
state: Georgia
city: Indianapolis
country: United States
facility: Thomas A. Cuilla, MD, PC at Midwest Eye Institute
state: Indiana
city: Portsmouth
country: United States
facility: Eyesight Ophthalmic Services, PA
state: New Hampshire
city: Toms River
country: United States
facility: Retina Vitreous Center
state: New Jersey
city: Charlotte
country: United States
facility: Southeast Clinical Research Associates, LLC
state: North Carolina
city: Rapid City
country: United States
facility: Black Hills Regioinal Eye Institute
state: South Dakota
city: Nashville
country: United States
facility: Tennessee Retina, PC
state: Tennessee
city: Austin
country: United States
facility: Retina Research Center
state: Texas
city: Houston
country: United States
facility: Retinal Consultants of Houston
state: Texas
city: McAllen
country: United States
facility: Valley Retina Institute
state: Texas
city: San Antonio
country: United States
facility: Retinal Consultants of San Antonio
state: Texas
city: Richmond
country: United States
facility: Retinal Institute of Virginia
state: Virginia
city: Gent
country: Belgium
facility: University Hospital Ghent
city: Laken
country: Belgium
facility: Brugmann Ziekenhuis
city: Brno
country: Czech Republic
facility: Fakultni nemocnice Brno
city: Kralove
country: Czech Republic
facility: Fakultní nemocnice Hradec Kralove
city: Ostrava
country: Czech Republic
facility: Fakultní nemocnice Ostrava
city: Zlín
country: Czech Republic
facility: GEMINI oční centrum, a.s
city: Ahaus
country: Germany
facility: Augenärzte Gemeinschaftspraxis Ahaus-Gronau-Lingen-Münster-Bad Bentheim
city: Darmstadt
country: Germany
facility: Augenklinik Klinikum Darmstadt
city: Ludwigshafen
country: Germany
facility: Klinikum der Stadt Ludwigshafen
city: Muenster
country: Germany
facility: Augenklinik am St. Franziskus-Hospital Muenster
city: München
country: Germany
facility: Klinik und Poliklinik für Augenheilkunde Klinikum rechts der Isar
city: Beer Sheva
country: Israel
facility: Soroka University Medical Center
city: Haifa
country: Israel
facility: Bnai Zion Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Ein Kerem Medical Center
city: Kfar Saba
country: Israel
facility: Meir Medical Center
city: Petah Tiqva
country: Israel
facility: Rabin Medical Center
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Tel-Hashomer
country: Israel
facility: The Chaim Sheba Medical Center
city: Zerifin
country: Israel
facility: Assaf Harofe Medical Center
city: Bydgoszcz
country: Poland
facility: Oftalmika
city: Bytom
country: Poland
facility: Szpital Specjalistyczny Nr 1 w Bytomiu
city: Gdańsk
country: Poland
facility: Profesorskie Centrum Okulistyki, Hipermarket Tesco
city: Wroclaw
country: Poland
facility: Spectrum OOK
city: Shirley
country: United Kingdom
facility: Southamptom Eye Unit, Southampton Hospital
state: Southampton
city: Frimley
country: United Kingdom
facility: Frimley Park Hospital NHS Foundation Trust
state: Surrey
city: Belfast
country: United Kingdom
facility: Eye and Ear Clinicl, The Royal Victoria Hospital
city: Bristol
country: United Kingdom
facility: Bristol Eye Hospital
city: Leeds
country: United Kingdom
facility: St. James University Hospital
city: London
country: United Kingdom
facility: Moorfields Eye Hospital
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital, Eye Department
Study officials:
affiliation: Quark Pharmaceuticals
name: Rabia Ozden, MD
role: STUDY_DIRECTOR
References: