Regorafenib Eye Drops: Investigation of Efficacy and Safety in Neovascular Age Related Macular Degeneration (DREAM)

A Combined Phase IIa / IIb Study of the Efficacy, Safety, and Tolerability of Repeated Topical Doses of Regorafenib Eye Drops, in Treatment-naïve Subjects With Neovascular Age Related Macular Degeneration

Part A (Phase IIa):

Primary objectives:

The study part A is designed to investigate whether the use of regorafenib eye drops can help patients with neovascular (wet) Age-Related Macular Degeneration (wAMD) to see better after 4 weeks and 12 weeks after inclusion into this study.

Secondary objectives:

The study will also evaluate the safety and tolerability of the regorafenib eye drops.

Part B (Phase IIb):

Primary objectives:

The study part B is designed to investigate:

• how often the regorafenib eye drops need to be given per day
• whether the use of regorafenib eye drops can help patients with neovascular (wet) Age-Related Macular Degeneration (wAMD) to see better after 4 weeks and 12 weeks after inclusion into this study.

Secondary objectives:

The study will also evaluate how the different dosings of regorafenib eye drops affect patients vision, the safety and the tolerability.

Study Overview

• Status: Terminated
• Conditions: Macular Degeneration
• Intervention / Treatment: Drug: Placebo; Drug: Regorafenib, ophthalmic oily suspension (BAY73-4506); Procedure: Sham IVT; Drug: Ranibizumab

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Parramatta, Australia, 2150
  • New South Wales
    • Strathfield, New South Wales, Australia, 2135
    • Sydney, New South Wales, Australia, 2000
    • Westmead, New South Wales, Australia, 2145
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
• Austria
  • Wien, Austria, 1130
  • Wien, Austria, 1090
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2H 0C8
    • Edmonton, Alberta, Canada, T5H 0X5
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 3N9
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
  • Ontario
    • London, Ontario, Canada, N6A 4V2
    • Mississauga, Ontario, Canada, L4W 1W9
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
    • Montreal, Quebec, Canada, H4P 2S4
    • Sherbrooke, Quebec, Canada, J1J 2B8
• Chile
  • Santiago, Chile, 8380456
  • Los Lagos
    • Osorno, Los Lagos, Chile, 5311138
  • Santiago
    • Metropolitana, Santiago, Chile, 7510168
    • Vitacura, Santiago, Chile, 7650710
• Colombia
  • Distrito Capital de Bogotá
    • Bogota, Distrito Capital de Bogotá, Colombia
• Czech Republic
  • Hradec Kralove, Czech Republic, 500 05
  • Praha 2, Czech Republic, 128 08
  • Praha 4, Czech Republic, 140 00
  • Praha 7, Czech Republic, 170 00
• France
  • Boredaux, France, 33076
  • Lyon, France, 69003
  • Cedex 12
    • Paris, Cedex 12, France, 75557
• Germany
  • Berlin, Germany, 12203
  • Hamburg, Germany, 20251
  • Baden-Württemberg
    • Tübingen, Baden-Württemberg, Germany, 72076
  • Bayern
    • München, Bayern, Germany, 81675
    • München, Bayern, Germany, 81377
  • Nordrhein-Westfalen
    • Bonn, Nordrhein-Westfalen, Germany, 53105
    • Köln, Nordrhein-Westfalen, Germany, 50937
    • Münster, Nordrhein-Westfalen, Germany, 48145
  • Rheinland-Pfalz
    • Mainz, Rheinland-Pfalz, Germany, 55131
  • Sachsen
    • Dresden, Sachsen, Germany, 01067
    • Dresden, Sachsen, Germany, 01307
    • Leipzig, Sachsen, Germany, 04103
• Hong Kong
  • Hong Kong, Hong Kong
  • Kowloon, Hong Kong
• Hungary
  • Budapest, Hungary, 1082
  • Budapest, Hungary, 1106
  • Budapest, Hungary, 1133
  • Debrecen, Hungary, 4032
  • Pecs, Hungary, 7621
• Israel
  • Afula, Israel, 1834111
  • Beer Sheva, Israel, 8410101
  • Haifa, Israel, 3109601
  • Haifa, Israel, 3436212
  • Jerusalem, Israel, 9112001
  • Kfar Saba, Israel, 4428164
  • Petah Tikva, Israel, 4941492
  • Ramat Gan, Israel, 5262000
  • Rehovot, Israel, 7610001
  • Tel Aviv, Israel, 6423906
  • Zerifin, Israel, 6093000
• Italy
  • Ancona, Italy, 60126
  • Bologna, Italy, 40138
  • Milano, Italy, 20132
  • Sassari, Italy, 07100
  • Friuli-Venezia Giulia
    • Udine, Friuli-Venezia Giulia, Italy, 33100
  • Lazio
    • Roma, Lazio, Italy, 00198
    • Roma, Lazio, Italy, 00133
  • Lombardia
    • Milano, Lombardia, Italy, 20157
    • Milano, Lombardia, Italy, 20122
  • Toscana
    • Firenze, Toscana, Italy, 50134
  • Veneto
    • Padova, Veneto, Italy, 35128
• Japan
  • Fukuoka, Japan, 812-0011
  • Kumamoto, Japan, 860-0027
  • Nagasaki, Japan, 852-8511
  • Nara, Japan, 630-8305
  • Osaka, Japan, 530-0001
  • Osaka, Japan, 533-0024
  • Chiba
    • Inba-gun, Chiba, Japan, 285-0922
  • Fukuoka
    • Miyako-gun, Fukuoka, Japan, 800-0344
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 004-0041
    • Sapporo, Hokkaido, Japan, 060-8604
  • Hyogo
    • Himeji, Hyogo, Japan, 671-1227
  • Kanagawa
    • Yamato, Kanagawa, Japan, 242-0001
    • Yokohama, Kanagawa, Japan, 222-0011
  • Mie
    • Iga, Mie, Japan, 518-0842
  • Tokyo
    • Chofu, Tokyo, Japan, 182-0024
    • Itabashi-ku, Tokyo, Japan, 173-0015
    • Ota-ku, Tokyo, Japan, 143-0013
    • Taito-ku, Tokyo, Japan, 111-0051
• Korea, Republic of
  • Busan, Korea, Republic of, 49241
  • Incheon, Korea, Republic of, 405-760
  • Seoul, Korea, Republic of, 137-701
  • Seoul, Korea, Republic of, 03080
  • Seoul, Korea, Republic of, 135-710
  • Seoul, Korea, Republic of, 05505
  • Gyeonggido
    • Seongnam-si, Gyeonggido, Korea, Republic of, 463-707
• Slovakia
  • Bratislava, Slovakia, 85107
  • Ruzomberok, Slovakia, 03426
  • Trencin, Slovakia, 91171
  • Zilina, Slovakia, 01207
  • Zilina, Slovakia, 01008
• Spain
  • Albacete, Spain, 02006
  • Barcelona, Spain, 08035
  • Sevilla, Spain, 41013
  • Sevilla, Spain, 41071
  • Valencia, Spain, 46014
  • Valencia, Spain, 46015
  • Valladolid, Spain, 47012
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
    • San Cugat del Vallès, Barcelona, Spain, 08190
  • Vizcaya
    • Barakaldo, Vizcaya, Spain, 48903
• Switzerland
  • Bern, Switzerland, 3010
  • Lausanne, Switzerland, 1004
  • Zürich, Switzerland, 8063
• United States
  • Arizona
    • Tucson, Arizona, United States, 85704
  • California
    • Arcadia, California, United States, 91007
    • Beverly Hills, California, United States, 90211
    • Campbell, California, United States, 95008
    • Costa Mesa, California, United States, 92626
    • Laguna Hills, California, United States, 92653
    • Mountain View, California, United States, 94040
    • Santa Ana, California, United States, 92705
  • Colorado
    • Golden, Colorado, United States, 80401
  • Florida
    • Boynton Beach, Florida, United States, 33426
    • Fort Myers, Florida, United States, 33912
    • Miami, Florida, United States, 33143
    • Plantation, Florida, United States, 33324
    • Sarasota, Florida, United States, 34239
    • Stuart, Florida, United States, 34994
    • Winter Haven, Florida, United States, 33880
  • Georgia
    • Decatur, Georgia, United States, 30030
  • Indiana
    • New Albany, Indiana, United States, 47150
  • Kansas
    • Leawood, Kansas, United States, 66211
    • Wichita, Kansas, United States, 67226
  • Kentucky
    • Louisville, Kentucky, United States, 40207
  • Louisiana
    • Eunice, Louisiana, United States, 70535
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
  • Michigan
    • Grand Rapids, Michigan, United States, 49525
  • Missouri
    • Florissant, Missouri, United States, 63031
  • New Jersey
    • Teaneck, New Jersey, United States, 07666
  • North Carolina
    • Asheville, North Carolina, United States, 28803
  • Pennsylvania
    • West Mifflin, Pennsylvania, United States, 15122
  • South Carolina
    • Greenville, South Carolina, United States, 29605
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
  • Texas
    • Austin, Texas, United States, 78705
    • Houston, Texas, United States, 77030
    • McAllen, Texas, United States, 78503
    • San Antonio, Texas, United States, 78240
    • Temple, Texas, United States, 76508
    • The Woodlands, Texas, United States, 77384
  • Virginia
    • Charlottesville, Virginia, United States, 22908

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Able to read (or, if unable to read due to visual impairment, be read to verbatim by the person administering the informed consent or a family member) and able to understand the informed consent form (ICF)
• Men and women ≥ 50 years of age
• Active primary subfoveal CNV (Choroidal neovascularization) lesions secondary to AMD (Age-related macular degeneration), including juxtafoveal lesions that affect the fovea as evidenced by FA (Fluorescein angiography) in the study eye and reviewed by the central reading center
• The area of CNV must occupy at least 50% of total lesion in the study eye, as determined by FA review at the central reading center
• Evidence of intraretinal and/or subretinal fluid on OCT (Optical coherence tomography)
• Early Treatment Diabetic Retinopathy Study BCVA of 73 to 25 letters (20/40 to 20/320 Snellen equivalent) in the study eye
• Willing, committed, and able to return for all clinic visits and complete all study related procedures
• Women of childbearing potential and men must agree to use adequate contraception when sexually active. This applies since signing of the ICF until one month after the EOS (end of study) visit. The definition of adequate contraception will be based on the judgment of the investigator.

Exclusion Criteria:

• Concurrent disease in the study eye, other than AMD (e.g., corneal diseases and dystrophies, conjunctival diseases, eye lid abnormalities, or any other diseases of the cornea and macula, or optic nerve abnormality) that could compromise visual acuity, likely require medical or surgical intervention during the study period, would limit the potential to gain or lose vision during study treatment, or could otherwise confound interpretation of the results
• Total lesion size (including neovascularization, scar, blood) > 12 disc areas (30.5 mm2) as assessed by FA
• Only one functional eye, even if that eye is otherwise eligible for the study
• Prior ocular or systemic treatment or surgery for neovascular AMD in the study eye except dietary supplements or vitamins
• Prior treatment with any systemic anti-VEGF (Vascular endothelial growth factor) agent
• Use of systemic or ocular treatment with an investigational drug within 12 weeks prior to start of study treatment
• Any other condition that would require frequent chronic co-administration of other topical eye medications that would interfere with study drug administration (e.g. contact lens)
• Symptoms or conditions consistent with contraindications listed in the current local label for ranibizumab
• Participation in an investigational study within 30 days prior to start of study treatment that involved treatment with any drug (excluding vitamins and minerals) or device
• Lactating women and women of child-bearing potential with either a positive pregnancy test result or no pregnancy test at screening are excluded. Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of child bearing potential.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Regorafenib [A]; Part A: Patients will receive Regorafenib eye drops	Drug: Regorafenib, ophthalmic oily suspension (BAY73-4506); Subjects receive Regorafenib as eye drops
EXPERIMENTAL: Regorafenib [B1]; Part B: Regorafenib eye drops dose 1; plus sham IVT (Intravitreal therapy) once every 4 weeks	Drug: Regorafenib, ophthalmic oily suspension (BAY73-4506); Subjects receive Regorafenib as eye drops; Procedure: Sham IVT; Sham injections
EXPERIMENTAL: Regorafenib [B2]; Part B: Regorafenib eye drops dose 2; plus sham IVT (Intravitreal therapy) once every 4 weeks	Drug: Regorafenib, ophthalmic oily suspension (BAY73-4506); Subjects receive Regorafenib as eye drops; Procedure: Sham IVT; Sham injections
EXPERIMENTAL: Regorafenib [B3]; Part B: Regorafenib eye drops dose 3; plus sham IVT (Intravitreal therapy) once every 4 weeks	Drug: Regorafenib, ophthalmic oily suspension (BAY73-4506); Subjects receive Regorafenib as eye drops; Procedure: Sham IVT; Sham injections
EXPERIMENTAL: Regorafenib [B4]; Part B: Regorafenib eye drops dose 4; plus sham IVT (Intravitreal therapy) once every 4 weeks	Drug: Regorafenib, ophthalmic oily suspension (BAY73-4506); Subjects receive Regorafenib as eye drops; Procedure: Sham IVT; Sham injections
EXPERIMENTAL: Regorafenib [B5]; Part B: Regorafenib eye drops dose 5; plus sham IVT (Intravitreal therapy) once every 4 weeks	Drug: Regorafenib, ophthalmic oily suspension (BAY73-4506); Subjects receive Regorafenib as eye drops; Procedure: Sham IVT; Sham injections
EXPERIMENTAL: Regorafenib [B6]; Part B: Regorafenib eye drops dose 6; plus sham IVT (Intravitreal therapy) once every 4 weeks	Drug: Regorafenib, ophthalmic oily suspension (BAY73-4506); Subjects receive Regorafenib as eye drops; Procedure: Sham IVT; Sham injections
ACTIVE_COMPARATOR: Ranibizumab; Ranibizumab IVT once every 4 weeks; plus placebo eye drops to match the regorafenib eye drop regimens	Drug: Placebo; Placebo eye drops; Drug: Ranibizumab; Subjects receive Ranibizumab as intravitreal injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Best Corrected Visual Acuity (BCVA) as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letter Score at Study Week 4 for Study Part A	Participants will be assessed at each clinic visit for best corrected visual acuity using the early treatment diabetic retinopathy study chart. Visual function of the study eye and the fellow eye was assessed using the ETDRS. The participant's ETDRS testing score was recorded in the appropriate eCRF page at each study visit. For participants that dropped out or received rescue treatment the last observation before drop-out or administration of rescue treatment was carried forward. A higher score represents better functioning.	Baseline, Week 4
Change From Baseline in BCVA as Measured by ETDRS Letter Score at Study Week 12 for Study Part A	Participants were assessed at each clinic visit for best corrected visual acuity using the early treatment diabetic retinopathy study chart. Visual function of the study eye and the fellow eye was assessed using the ETDRS protocol. ETDRS testing score was recorded in the appropriate eCRF page at each study visit. For participants that dropped out or received rescue treatment the last observation before drop-out or administration of rescue treatment was carried forward. A higher score represents better functioning.	Baseline, Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Individual Changes in BCVA of Greater Than Equal to (>=) 0 Letters of Vision From Study Week 4 to Week 12 for Study Part A	Participants were assessed at each clinic visit for BCVA using the early treatment diabetic retinopathy study chart. For participants that dropped out or received rescue treatment the last observation before drop-out or administration of rescue treatment was carried forward.	Week 4, Week 12
Percentage of Participants With a Loss in BCVA of >= 10 Letters From Baseline to Study Week 12 for Study Part A	Participants were assessed at each clinic visit for BCVA using the early treatment diabetic retinopathy study chart. For participants that dropped out or received rescue treatment the last observation before drop-out or administration of rescue treatment was carried forward.	Baseline, Week 12

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (ACTUAL): May 1, 2015
• Study Completion (ACTUAL): June 1, 2015

Study Registration Dates

• First Submitted: August 20, 2014
• First Submitted That Met QC Criteria: August 20, 2014
• First Posted (ESTIMATE): August 21, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): September 8, 2016
• Last Update Submitted That Met QC Criteria: July 25, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: neovascular Age-related Macular Degeneration
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Wet Macular Degeneration; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Ranibizumab
• Other Study ID Numbers: 15984; 2012-003763-22 (EUDRACT_NUMBER)