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

February 3, 2015 updated by: Quark Pharmaceuticals

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)

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
258

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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: PF-04523655 (Stratum II)
6 monthly IVT injections of PF-04523655 (a small interfering RNA)
Other Names:
  • PF-655
Drug: ranibizumab
6 monthly IVT injections of ranibizumab (Stratum II)
Other Names:
  • Lucentis
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
6 months post-injection
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
6 months post-injection
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)
30 days after the last injection
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
30 days after the last injection

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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)
30 days after the last injection

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Quark Pharmaceuticals

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Rabia Ozden, MD, Quark Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2012

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2013

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2013

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 30, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 3, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 4, 2011

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 23, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 3, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • QRK202
  • 2011-004157-66 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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