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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Quark Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01445899
First received: September 30, 2011
Last updated: March 28, 2014
Last verified: March 2014
  Purpose

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 Intervention Phase
Choroidal Neovascularization
Diabetic Retinopathy
Diabetic Macular Edema
Drug: PF-04523655 (Stratum I)
Drug: PF-04523655 and ranibizumab
Drug: ranibizumab
Drug: PF-04523655 (Stratum II)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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)

Resource links provided by NLM:


Further study details as provided by Quark Pharmaceuticals:

Primary Outcome Measures:
  • Safety and dose-limiting toxicities (Stratum I) [ Time Frame: 6 months post-injection ] [ Designated as safety issue: No ]
    - 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 ] [ Designated as safety issue: No ]
    - 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 ] [ Designated as safety issue: No ]
    - 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 ] [ Designated as safety issue: No ]
    - 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:
  • Anatomical changes in retina and retinal nerve fiber layer morphology (Stratum II) [ Time Frame: 30 days after the last injection ] [ Designated as safety issue: No ]
    - 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)


Enrollment: 258
Study Start Date: February 2012
Study Completion Date: November 2013
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PF-04523655 (Stratum II)
Stratum II
Drug: PF-04523655 (Stratum II)
PF-04523655 - 6 monthly IVT injections
Experimental: PF-04523655 and ranibizumab
Stratum II
Drug: PF-04523655 and ranibizumab
6 monthly IVT injections of PF-04523655 in combination with ranibizumab (Stratum II)
Active Comparator: ranibizumab
Stratum II
Drug: ranibizumab
6 monthly IVT injections of ranibizumab alone (Stratum II)
Other Name: Lucentis
Experimental: PF-04523655 (Stratum I)
Stratum I
Drug: PF-04523655 (Stratum I)
PF-04523655 (a small interfering RNA) - a single IVT injection

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01445899

  Show 51 Study Locations
Sponsors and Collaborators
Quark Pharmaceuticals
Investigators
Study Director: Rabia Ozden, MD Quark Pharmaceuticals
  More Information

No publications provided

Responsible Party: Quark Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01445899     History of Changes
Other Study ID Numbers: QRK202, 2011-004157-66
Study First Received: September 30, 2011
Last Updated: March 28, 2014
Health Authority: United States: Food and Drug Administration
Israel: Ministry of Health

Additional relevant MeSH terms:
Choroidal Neovascularization
Diabetic Retinopathy
Edema
Macular Edema
Neovascularization, Pathologic
Cardiovascular Diseases
Choroid Diseases
Diabetes Complications
Diabetes Mellitus
Diabetic Angiopathies
Endocrine System Diseases
Eye Diseases
Macular Degeneration
Metaplasia
Pathologic Processes
Retinal Degeneration
Retinal Diseases
Signs and Symptoms
Uveal Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on November 19, 2014