NCT01445899

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.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
258

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Feb 2012

Geographic Reach
7 countries

51 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 30, 2011

Completed
4 days until next milestone

First Posted

Study publicly available on registry

October 4, 2011

Completed
4 months until next milestone

Study Start

First participant enrolled

February 1, 2012

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2013

Completed
Last Updated

February 23, 2015

Status Verified

February 1, 2015

Enrollment Period

1.8 years

First QC Date

September 30, 2011

Last Update Submit

February 3, 2015

Conditions

Outcome Measures

Primary Outcomes (4)

  • 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

  • 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

  • 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

  • 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

Secondary Outcomes (1)

  • Anatomical changes in retina and retinal nerve fiber layer morphology (Stratum II)

    30 days after the last injection

Study Arms (4)

PF-04523655 (Stratum II)

EXPERIMENTAL

Stratum II, 6 monthly injections of PF-04523655 only

Drug: PF-04523655 (Stratum II)

PF-04523655 and ranibizumab

EXPERIMENTAL

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

Drug: ranibizumabDrug: PF-04523655 (Stratum II)

ranibizumab

ACTIVE COMPARATOR

Stratum II, 6 monthly IVT injections of ranibizumab only

Drug: ranibizumab

PF-04523655 (Stratum I)

EXPERIMENTAL

Stratum I

Drug: PF-04523655 (Stratum I)

Interventions

PF-04523655 (a small interfering RNA) - a single IVT injection

Also known as: PF-655
PF-04523655 (Stratum I)

6 monthly IVT injections of ranibizumab (Stratum II)

Also known as: Lucentis
PF-04523655 and ranibizumabranibizumab

6 monthly IVT injections of PF-04523655 (a small interfering RNA)

Also known as: PF-655
PF-04523655 (Stratum II)PF-04523655 and ranibizumab

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Visual acuity in the study eye ≤ 20/200.
  • Low visual acuity is the result of an irreversible condition affecting the posterior segment of the study eye.

You may not qualify if:

  • History of vitrectomy.
  • History of IVT injection in study eye within last 6 months.
  • History of vitreous hemorrhage, retinal detachment, or invasive trauma in study eye.
  • History of uveitis or endophthalmitis in either eye.
  • Any active inflammatory condition in study eye.
  • Received any drugs known to cause optic nerve or retinal toxicity within 14 days prior to dosing.
  • 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.
  • Intraocular pressure in either eye ≥25 mmHg on maximal medication.
  • Cataract surgery and laser corneal surgery within 3 months prior to dosing in the study eye and all other intraocular surgeries at any time.
  • Participation in a concurrent interventional study within 30 days prior to dosing.
  • History of diabetes mellitus (Type 1 or Type 2).
  • Retinal thickening secondary to the edema caused by diabetes mellitus.
  • Best corrected visual acuity (BCVA) of 20/40 or worse and up to 20/320 or better in the study eye at Screening.
  • 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).
  • History of panretinal photocoagulation within 6 months or macular laser photocoagulation within 3 months of prior to dosing in the study eye.
  • +14 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (51)

Retina Consultants of Arizona

Phoenix, Arizona, 85014, United States

Location

Retina Institute of California

Arcadia, California, 91007, United States

Location

Retina-Vitreous Associates

Beverly Hills, California, 90211, United States

Location

Retina Diagnostic Center

Campbell, California, 95008, United States

Location

Retinal Consultants Medical Group, Inc.

Sacramento, California, 95819, United States

Location

Orange County Reina Medical Group

Santa Ana, California, 92705, United States

Location

MedEye Associates

Miami, Florida, 33143, United States

Location

Center for Retina and Macular Disease

Winter Haven, Florida, 33880, United States

Location

Southeast Retina Center

Augusta, Georgia, 30909, United States

Location

Thomas A. Cuilla, MD, PC at Midwest Eye Institute

Indianapolis, Indiana, 46290, United States

Location

Eyesight Ophthalmic Services, PA

Portsmouth, New Hampshire, 03801, United States

Location

Retina Vitreous Center

Toms River, New Jersey, 08755, United States

Location

Southeast Clinical Research Associates, LLC

Charlotte, North Carolina, 28210, United States

Location

Black Hills Regioinal Eye Institute

Rapid City, South Dakota, 57701, United States

Location

Tennessee Retina, PC

Nashville, Tennessee, 37203, United States

Location

Retina Research Center

Austin, Texas, 78705, United States

Location

Retinal Consultants of Houston

Houston, Texas, 77030, United States

Location

Valley Retina Institute

McAllen, Texas, 78503, United States

Location

Retinal Consultants of San Antonio

San Antonio, Texas, 78204, United States

Location

Retinal Institute of Virginia

Richmond, Virginia, 23235, United States

Location

University Hospital Ghent

Ghent, Belgium, 9000, Belgium

Location

Brugmann Ziekenhuis

Laken, Belgium, 1020, Belgium

Location

Fakultni nemocnice Brno

Brno, Czech Republic, 62500, Czechia

Location

Fakultní nemocnice Hradec Kralove

Kralove, Czech Republic, 50005, Czechia

Location

Fakultní nemocnice Ostrava

Ostrava, Czech Republic, 70852, Czechia

Location

GEMINI oční centrum, a.s

Zlín, Czech Republic, 76001, Czechia

Location

Augenärzte Gemeinschaftspraxis Ahaus-Gronau-Lingen-Münster-Bad Bentheim

Ahaus, Germany, 48683, Germany

Location

Augenklinik Klinikum Darmstadt

Darmstadt, Germany, 64297, Germany

Location

Klinikum der Stadt Ludwigshafen

Ludwigshafen, Germany, 67063, Germany

Location

Klinik und Poliklinik für Augenheilkunde Klinikum rechts der Isar

München, Germany, 81675, Germany

Location

Augenklinik am St. Franziskus-Hospital Muenster

Münster, Germany, 48145, Germany

Location

Soroka University Medical Center

Beersheba, Israel, 84101, Israel

Location

Bnai Zion Medical Center

Haifa, Israel, 31048, Israel

Location

Meir Medical Center

Kfar Saba, Israel, 44281, Israel

Location

The Chaim Sheba Medical Center

Tel Litwinsky, Israel, 52621, Israel

Location

Hadassah Ein Kerem Medical Center

Jerusalem, Israel

Location

Rabin Medical Center

Petah Tikva, Israel

Location

Kaplan Medical Center

Rehovot, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, Israel

Location

Assaf Harofe Medical Center

Ẕerifin, Israel

Location

Oftalmika

Bydgoszcz, Poland, 85631, Poland

Location

Szpital Specjalistyczny Nr 1 w Bytomiu

Bytom, Poland, 41902, Poland

Location

Profesorskie Centrum Okulistyki, Hipermarket Tesco

Gdansk, Poland, 80809, Poland

Location

Spectrum OOK

Wroclaw, Poland, 51-646, Poland

Location

Southamptom Eye Unit, Southampton Hospital

Shirley, Southampton, SO16 6YD, United Kingdom

Location

Frimley Park Hospital NHS Foundation Trust

Frimley, Surrey, GU16 7UJ, United Kingdom

Location

Eye and Ear Clinicl, The Royal Victoria Hospital

Belfast, United Kingdom, BT12 6BA, United Kingdom

Location

Bristol Eye Hospital

Bristol, United Kingdom, BS1 2LX, United Kingdom

Location

St. James University Hospital

Leeds, United Kingdom, LS9 7TF, United Kingdom

Location

Moorfields Eye Hospital

London, United Kingdom, EC1V 2PD, United Kingdom

Location

Royal Hallamshire Hospital, Eye Department

Sheffield, United Kingdom, S10 2JF, United Kingdom

Location

MeSH Terms

Conditions

Choroidal NeovascularizationDiabetic Retinopathy

Interventions

PF-04523655Ranibizumab

Condition Hierarchy (Ancestors)

Choroid DiseasesUveal DiseasesEye DiseasesNeovascularization, PathologicMetaplasiaPathologic ProcessesPathological Conditions, Signs and SymptomsRetinal DiseasesDiabetic AngiopathiesVascular DiseasesCardiovascular DiseasesDiabetes ComplicationsDiabetes MellitusEndocrine System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Rabia Ozden, MD

    Quark Pharmaceuticals

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 30, 2011

First Posted

October 4, 2011

Study Start

February 1, 2012

Primary Completion

November 1, 2013

Study Completion

November 1, 2013

Last Updated

February 23, 2015

Record last verified: 2015-02

Locations