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

Sponsor
Quark Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01445899
Collaborator
(none)
258
Enrollment
51
Locations
4
Arms
21
Duration (Months)
5.1
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

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 Design

Study Type:
Interventional
Actual Enrollment :
258 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
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 Start Date :
Feb 1, 2012
Actual Primary Completion Date :
Nov 1, 2013
Actual Study Completion Date :
Nov 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: PF-04523655 (Stratum II)

Stratum II, 6 monthly injections of PF-04523655 only

Drug: PF-04523655 (Stratum II)
6 monthly IVT injections of PF-04523655 (a small interfering RNA)
Other Names:
  • PF-655

    		•
    Experimental: PF-04523655 and ranibizumab

    Stratum II, 6 monthly injections of PF-0423655 and ranibizumab administered in combination

    Drug: ranibizumab
    6 monthly IVT injections of ranibizumab (Stratum II)
    Other Names:
  • Lucentis

    • Drug: PF-04523655 (Stratum II)
    6 monthly IVT injections of PF-04523655 (a small interfering RNA)
    Other Names:
  • PF-655

    		•
    Active Comparator: ranibizumab

    Stratum II, 6 monthly IVT injections of ranibizumab only

    Drug: ranibizumab
    6 monthly IVT injections of ranibizumab (Stratum II)
    Other Names:
  • Lucentis

    		•
    Experimental: PF-04523655 (Stratum I)

    Stratum I

    Drug: PF-04523655 (Stratum I)
    PF-04523655 (a small interfering RNA) - a single IVT injection
    Other Names:
  • PF-655

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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

    2. 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

    3. 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)

    4. 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

    Secondary Outcome Measures

    1. 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)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Retina Consultants of Arizona Phoenix Arizona United States 85014
    2 Retina Institute of California Arcadia California United States 91007
    3 Retina-Vitreous Associates Beverly Hills California United States 90211
    4 Retina Diagnostic Center Campbell California United States 95008
    5 Retinal Consultants Medical Group, Inc. Sacramento California United States 95819
    6 Orange County Reina Medical Group Santa Ana California United States 92705
    7 MedEye Associates Miami Florida United States 33143
    8 Center for Retina and Macular Disease Winter Haven Florida United States 33880
    9 Southeast Retina Center Augusta Georgia United States 30909
    10 Thomas A. Cuilla, MD, PC at Midwest Eye Institute Indianapolis Indiana United States 46290
    11 Eyesight Ophthalmic Services, PA Portsmouth New Hampshire United States 03801
    12 Retina Vitreous Center Toms River New Jersey United States 08755
    13 Southeast Clinical Research Associates, LLC Charlotte North Carolina United States 28210
    14 Black Hills Regioinal Eye Institute Rapid City South Dakota United States 57701
    15 Tennessee Retina, PC Nashville Tennessee United States 37203
    16 Retina Research Center Austin Texas United States 78705
    17 Retinal Consultants of Houston Houston Texas United States 77030
    18 Valley Retina Institute McAllen Texas United States 78503
    19 Retinal Consultants of San Antonio San Antonio Texas United States 78204
    20 Retinal Institute of Virginia Richmond Virginia United States 23235
    21 University Hospital Ghent Gent Belgium 9000
    22 Brugmann Ziekenhuis Laken Belgium 1020
    23 Fakultni nemocnice Brno Brno Czech Republic 62500
    24 Fakultní nemocnice Hradec Kralove Kralove Czech Republic 50005
    25 Fakultní nemocnice Ostrava Ostrava Czech Republic 70852
    26 GEMINI oční centrum, a.s Zlín Czech Republic 76001
    27 Augenärzte Gemeinschaftspraxis Ahaus-Gronau-Lingen-Münster-Bad Bentheim Ahaus Germany 48683
    28 Augenklinik Klinikum Darmstadt Darmstadt Germany 64297
    29 Klinikum der Stadt Ludwigshafen Ludwigshafen Germany 67063
    30 Augenklinik am St. Franziskus-Hospital Muenster Muenster Germany 48145
    31 Klinik und Poliklinik für Augenheilkunde Klinikum rechts der Isar München Germany 81675
    32 Soroka University Medical Center Beer Sheva Israel 84101
    33 Bnai Zion Medical Center Haifa Israel 31048
    34 Hadassah Ein Kerem Medical Center Jerusalem Israel
    35 Meir Medical Center Kfar Saba Israel 44281
    36 Rabin Medical Center Petah Tiqva Israel
    37 Kaplan Medical Center Rehovot Israel
    38 Tel Aviv Sourasky Medical Center Tel Aviv Israel
    39 The Chaim Sheba Medical Center Tel-Hashomer Israel 52621
    40 Assaf Harofe Medical Center Zerifin Israel
    41 Oftalmika Bydgoszcz Poland 85631
    42 Szpital Specjalistyczny Nr 1 w Bytomiu Bytom Poland 41902
    43 Profesorskie Centrum Okulistyki, Hipermarket Tesco Gdańsk Poland 80809
    44 Spectrum OOK Wroclaw Poland 51-646
    45 Southamptom Eye Unit, Southampton Hospital Shirley Southampton United Kingdom SO16 6YD
    46 Frimley Park Hospital NHS Foundation Trust Frimley Surrey United Kingdom GU16 7UJ
    47 Eye and Ear Clinicl, The Royal Victoria Hospital Belfast United Kingdom BT12 6BA
    48 Bristol Eye Hospital Bristol United Kingdom BS1 2LX
    49 St. James University Hospital Leeds United Kingdom LS9 7TF
    50 Moorfields Eye Hospital London United Kingdom EC1V 2PD
    51 Royal Hallamshire Hospital, Eye Department Sheffield United Kingdom S10 2JF

    Sponsors and Collaborators

    • Quark Pharmaceuticals

    Investigators

    • Study Director: Rabia Ozden, MD, Quark Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Quark Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01445899
    Other Study ID Numbers:
    • QRK202
    • 2011-004157-66
    First Posted:
    Oct 4, 2011
    Last Update Posted:
    Feb 23, 2015
    Last Verified:
    Feb 1, 2015
    Additional relevant MeSH terms:
    Macular Edema
    Diabetic Retinopathy
    Choroidal Neovascularization
    Edema
    Neovascularization, Pathologic
    Ranibizumab

    Study Results

    No Results Posted as of Feb 23, 2015