Study of the Efficacy and Safety of the Ranibizumab Port Delivery System for Sustained Delivery of Ranibizumab in Patients With Subfoveal Neovascular Age-Related Macular Degeneration

NCT02510794 | Completed Phase 2 Results

• 1 other identifier: GX28228
• Study Type: interventional
• Target: 225
• Locations: 1 country
• Sites: 50

Brief Summary

This is a Phase II multicenter, dose-ranging, randomized, active treatment (monthly ITV injection)-controlled study to evaluate the efficacy, safety, and pharmacokinetics of ranibizumab delivered through the Implant using three ranibizumab formulation arms (10 mg/mL, 40 mg/mL, and 100 mg/mL) compared with the control arm (0.5-mg monthly ITV injections of 10-mg/mL formulation) in participants with subfoveal neovascular age-related macular degeneration (nAMD).

Conditions

Macular Degeneration

Outcome Measures

Primary Outcomes (1)

• Time Until a Participant First Requires the Implant Refill According to Protocol-Defined Refill Criteria

  Protocol-Defined Refill Criteria At 1 month after initial fill: * Decrease of ≥ 10 letters in BCVA at the current visit compared with the baseline BCVA, due to nAMD disease activity OR * Increase in CFT of ≥ 100 um at the current visit compared with the baseline CFT, due to nAMD disease activity OR * Presence of new macular hemorrhage, due to nAMD disease activity For subsequent assessments: * Increase in CFT of ≥ 75 μm on SD-OCT at the current visit compared with the average CFT over the last 2 available measurements, due to nAMD disease activity OR * Increase in CFT of ≥ 100 um from the lowest CFT measurement on study, due to nAMD disease activity OR * Decrease of ≥ 5 letters in BCVA at the current visit compared with the average BCVA over the last 2 available measurements, due to nAMD disease activity OR * Decrease of ≥ 10 letters from best recorded BCVA on study, due to nAMD disease activity OR * Presence of new macular hemorrhage, due to nAMD disease activity

  Baseline up to approximately 38 months

Secondary Outcomes (12)

• Change From Baseline in Best Corrected Visual Acuity (BCVA) Averaged At Month 9 and 10

  Baseline, Months 9, 10

• Change From Baseline in BCVA Over Time

  Baseline up to Month 10

• Adjusted Average Change From Baseline in BCVA Over Time (MMRM Analysis)

  Baseline up to Month 10

• Change From Baseline in Central Foveal Thickness (CFT) Over Time as Assessed on Spectral Domain-Optical Coherence Tomography (SD-OCT)

  Baseline up to Month 9

• Number of Implant Clogging at Month 9

  Month 9

Study Arms (4)

Port Delivery System with Ranibizumab 10mg/mL

EXPERIMENTAL

Participants had the Implant (prefilled with approximately 20 μL of 10-mg/mL ,approximately 0.2 mg dose, of ranibizumab) surgically inserted in the study eye at the Day 1 visit following their randomization visit. Starting at the Month 1 visit, participants were evaluated monthly for the need for Implant refill with the 10-mg/mL formulation of ranibizumab according to their randomization as per protocol-specified refill criteria.

Drug: Ranibizumab

Port Delivery System with Ranibizumab 40mg/mL

EXPERIMENTAL

Participants had the Implant (prefilled with approximately 20 μL of 40-mg/mL, approximately 0.8 mg dose, of ranibizumab) surgically inserted in the study eye at the Day 1 visit following their randomization visit. Starting at the Month 1 visit, participants were evaluated monthly for the need for Implant refill with the 40-mg/mL formulation of ranibizumab according to their randomization as per protocol-specified refill criteria.

Drug: Ranibizumab

Port Delivery System with Ranibizumab 100mg/mL

EXPERIMENTAL

Participants had the Implant (prefilled with approximately 20 μL of 100-mg/mL, approximately 2 mg dose, of ranibizumab) surgically inserted in the study eye at the Day 1 visit following their randomization visit. Starting at the Month 1 visit, participants were evaluated monthly for the need for Implant refill with the 100-mg/mL formulation of ranibizumab according to their randomization as per protocol-specified refill criteria.

Drug: Ranibizumab

Intravitreal Injection with Ranibizumab 0.5mg

ACTIVE COMPARATOR

Participants received ranibizumab 0.5 mg monthly ITV injections of 10 mg/mL formulation at Day 1 and every month thereafter.

Drug: Ranibizumab

Interventions

Ranibizumab DRUG

Ranibizumab will be administered at dose of 0.5 mg monthly ITV injections of 10-mg/mL formulation or delivered through the implant with three different formulations.

Also known as: Lucentis®

Intravitreal Injection with Ranibizumab 0.5mg; Port Delivery System with Ranibizumab 100mg/mL; Port Delivery System with Ranibizumab 10mg/mL; Port Delivery System with Ranibizumab 40mg/mL

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly diagnosed with wet AMD within 9 months of screening visit
• Participant must have received at least 2 prior ITV anti-vascular endothelial growth factor (VEGF) injections. However, the most recent anti-VEGF injection must have been ranibizumab and must have occurred at least 7 days prior to the screening visit
• Demonstrated response to prior ITV anti-VEGF treatment
• Best Corrected Visual Acuity (BCVA) using Early Treatment Diabetic Retinopathy Study (ETDRS) charts of 20/20-20/200 Snellen equivalent

You may not qualify if:

• Treatment with ITV anti-VEGF agents other than ranibizumab within 1 month prior to the randomization visit in either eye
• Study eye treatment with ITV anti-VEGF agents other than ranibizumab within 1 month prior to the randomization visit
• History of laser photocoagulation, Visudyne®, ITV corticosteroid injection, vitrectomy surgery, submacular surgery, device implantation, or other surgical intervention for AMD in the study eye
• Prior participation in a clinical trial involving anti-angiogenic drugs, other than ranibizumab, in either eye within 2 months of the randomization visit
• Subretinal hemorrhage in the study eye that involves the center of the fovea
• Subfoveal fibrosis, or atrophy in the study eye
• Choroidal neovascularization (CNV) in either eye due to other causes, such as ocular histoplasmosis, trauma, or pathologic myopia
• Uncontrolled ocular hypertension or glaucoma in the study eye
• History of glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery in the study eye
• Uncontrolled blood pressure
• Uncontrolled atrial fibrillation within 3 months of informed consent
• History of myocardial infarction or stroke within the last 3 months prior to informed consent
• History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of ranibizumab or placement of the Implant, that might affect interpretation of the results of the study or renders the participant at high risk of treatment complications
• Use of oral corticosteroids
• Current treatment for any active systemic infection

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (50)

Barnet Dulaney Perkins Eye Center

Mesa, Arizona, 85206, United States

Location

Retinal Research Institute, LLC

Phoenix, Arizona, 85014, United States

Location

Associated Retina Consultants

Phoenix, Arizona, 85020, United States

Location

The Retina Partners

Encino, California, 91436, United States

Location

Jacobs Retina center at the Shiley eye Institute UCSD

La Jolla, California, 92037, United States

Location

Jules Stein Eye Institute/ UCLA

Los Angeles, California, 90095-7000, United States

Location

N CA Retina Vitreous Assoc

Mountain View, California, 94040, United States

Location

Retinal Consultants Med Group

Sacramento, California, 95825, United States

Location

West Coast Retina Medical Group

San Francisco, California, 94109, United States

Location

UCSF; Ophthalmology

San Francisco, California, 94143, United States

Location

Orange County Retina Med Group

Santa Ana, California, 92705, United States

Location

California Retina Consultants

Santa Barbara, California, 93103, United States

Location

Retina Consultants of Southern

Colorado Springs, Colorado, 80909, United States

Location

Colorado Retina Associates, PC

Lakewood, Colorado, 80228, United States

Location

Florida Eye Microsurgical Inst

Boynton Beach, Florida, 33426, United States

Location

National Ophthalmic Research Institute

Fort Myers, Florida, 33912, United States

Location

Retina Specialty Institute

Pensacola, Florida, 32503, United States

Location

Retina Vitreous Assoc of FL

St. Petersburg, Florida, 33711, United States

Location

Retina Associates of Florida, LLC

Tampa, Florida, 33609, United States

Location

Southeast Retina Center

Augusta, Georgia, 30909, United States

Location

Illinois Retina Associates

Joliet, Illinois, 60435, United States

Location

Wolfe Eye Clinic

West Des Moines, Iowa, 50266, United States

Location

Retina Associates of Kentucky

Lexington, Kentucky, 40509, United States

Location

Paducah Retinal Center

Paducah, Kentucky, 42001, United States

Location

Johns Hopkins Med; Wilmer Eye Inst

Baltimore, Maryland, 21287, United States

Location

Retina Group of Washington

Chevy Chase, Maryland, 20815, United States

Location

Retina Specialists

Towson, Maryland, 21204, United States

Location

Vitreo-Retinal Associates, PC

Worcester, Massachusetts, 01605, United States

Location

Foundation for Vision Research

Grand Rapids, Michigan, 49546, United States

Location

Vitreoretinal Surgery

Edina, Minnesota, 55435, United States

Location

Sierra Eye Associates

Reno, Nevada, 89502, United States

Location

Retina Center of New Jersey

Bloomfield, New Jersey, 07003, United States

Location

Mid Atlantic Retina - Wills Eye Hospital

Cherry Hill, New Jersey, 08034, United States

Location

Eye Associates of New Mexico

Albuquerque, New Mexico, 87102, United States

Location

University of New Mexico; School of Med

Albuquerque, New Mexico, 87131, United States

Location

Retina Assoc of Western NY

Rochester, New York, 14620, United States

Location

Char Eye Ear &Throat Assoc

Charlotte, North Carolina, 28210, United States

Location

Cincinnati Eye Institute

Cincinnati, Ohio, 45242, United States

Location

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Retina Northwest

Portland, Oregon, 97221, United States

Location

Oregon HSU; Casey Eye Institute

Portland, Oregon, 97239, United States

Location

Palmetto Retina Center

Florence, South Carolina, 29501, United States

Location

Charles Retina Institute

Germantown, Tennessee, 38138, United States

Location

Tennessee Retina PC.

Nashville, Tennessee, 37203, United States

Location

Texas Retina Associates

Arlington, Texas, 76012, United States

Location

Retina Research Center

Austin, Texas, 78750, United States

Location

Retina Consultants of Texas

Bellaire, Texas, 77401, United States

Location

Med Center Ophthalmology Assoc

San Antonio, Texas, 78240, United States

Location

Retina Associates of Utah

Salt Lake City, Utah, 84107, United States

Location

Wagner Macula & Retina Center

Norfolk, Virginia, 23502, United States

Location

Related Publications (4)

• Campochiaro PA, Eichenbaum D, Chang MA, Clark WL, Graff JM, Le Pogam S, Cavichini Cordeiro M, Gune S, Rabena M, Singh N, Lin S, Callaway N. Interim Results of the Phase III Portal Extension Trial of the Port Delivery System with Ranibizumab in Neovascular Age-Related Macular Degeneration. Ophthalmol Retina. 2025 Feb;9(2):144-155. doi: 10.1016/j.oret.2024.05.021. Epub 2024 Aug 30.

  PMID: 39209113 DERIVED

• Wykoff CC, Campochiaro PA, Pieramici DJ, Khanani AM, Gune S, Maia M, Kagedal M, Ding HT, Maass KF. Pharmacokinetics of the Port Delivery System with Ranibizumab in the Ladder Phase 2 Trial for Neovascular Age-Related Macular Degeneration. Ophthalmol Ther. 2022 Oct;11(5):1705-1717. doi: 10.1007/s40123-022-00532-9. Epub 2022 Jun 27.

  PMID: 35759124 DERIVED

• Awh CC, Barteselli G, Makadia S, Chang RT, Stewart JM, Wieland MR, Brassard R, Callaway NF, Gune S, Heatherton P, Malhotra V, Willis JR, Pieramici DJ. Management of Key Ocular Adverse Events in Patients Implanted with the Port Delivery System with Ranibizumab. Ophthalmol Retina. 2022 Nov;6(11):1028-1043. doi: 10.1016/j.oret.2022.05.011. Epub 2022 May 16.

  PMID: 35589078 DERIVED

• Yohe S, Maass KF, Horvath J, Rea J, Barteselli G, Ranade SV. In-vitro characterization of ranibizumab release from the Port Delivery System. J Control Release. 2022 May;345:101-107. doi: 10.1016/j.jconrel.2022.03.005. Epub 2022 Mar 4.

  PMID: 35248647 DERIVED

MeSH Terms

Conditions

Macular Degeneration

Interventions

Ranibizumab

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: July 17, 2015
• First Posted: July 29, 2015
• Study Start: September 28, 2015
• Primary Completion: April 10, 2018
• Study Completion: March 28, 2019
• Last Updated: May 6, 2021
• Results First Posted: May 6, 2021

Record last verified: 2021-04

Locations

US (50)