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Macular DegenerationPhase 2LADDERNCT02510794

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

A Phase 2 study testing Ranibizumab in people with Macular Degeneration, run by Genentech, Inc. at 50 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 50 years and older
Conditions the study is for
Macular Degeneration
What is being tested?
Ranibizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
225 participants
Where
50 sitesUnited States
Study dates
28 Sep 2015to 28 Mar 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 19Show fewer
  • 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
  • Use of anticoagulants, anti-platelets (other than aspirin), or medications known to exert similar effects
  • Active malignancy within 12 months of randomization
  • History of allergy to fluorescein
  • Previous participation in any non-ocular (systemic) disease studies of investigational drugs within 1 month preceding the informed consent (excluding vitamins and minerals)

Trial locations and contacts

50 sites in 1 country.

50 sites in 1 country

United States50 sites

  • Eye Associates of New Mexico

    Albuquerque, New Mexico, 87102

  • University of New Mexico; School of Med

    Albuquerque, New Mexico, 87131

  • Texas Retina Associates

    Arlington, Texas, 76012

  • Southeast Retina Center

    Augusta, Georgia, 30909

  • Retina Research Center

    Austin, Texas, 78750

  • Johns Hopkins Med; Wilmer Eye Inst

    Baltimore, Maryland, 21287

  • Retina Consultants of Texas

    Bellaire, Texas, 77401

  • Retina Center of New Jersey

    Bloomfield, New Jersey, 07003

  • Florida Eye Microsurgical Inst

    Boynton Beach, Florida, 33426

  • Char Eye Ear &Throat Assoc

    Charlotte, North Carolina, 28210

  • Mid Atlantic Retina - Wills Eye Hospital

    Cherry Hill, New Jersey, 08034

  • Retina Group of Washington

    Chevy Chase, Maryland, 20815

  • Cincinnati Eye Institute

    Cincinnati, Ohio, 45242

  • The Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Retina Consultants of Southern

    Colorado Springs, Colorado, 80909

  • Vitreoretinal Surgery

    Edina, Minnesota, 55435

  • The Retina Partners

    Encino, California, 91436

  • Palmetto Retina Center

    Florence, South Carolina, 29501

  • National Ophthalmic Research Institute

    Fort Myers, Florida, 33912

  • Charles Retina Institute

    Germantown, Tennessee, 38138

  • Foundation for Vision Research

    Grand Rapids, Michigan, 49546

  • Illinois Retina Associates

    Joliet, Illinois, 60435

  • Jacobs Retina center at the Shiley eye Institute UCSD

    La Jolla, California, 92037

  • Colorado Retina Associates, PC

    Lakewood, Colorado, 80228

  • Retina Associates of Kentucky

    Lexington, Kentucky, 40509

  • Jules Stein Eye Institute/ UCLA

    Los Angeles, California, 90095-7000

  • Barnet Dulaney Perkins Eye Center

    Mesa, Arizona, 85206

  • N CA Retina Vitreous Assoc

    Mountain View, California, 94040

  • Tennessee Retina PC.

    Nashville, Tennessee, 37203

  • Wagner Macula & Retina Center

    Norfolk, Virginia, 23502

  • Paducah Retinal Center

    Paducah, Kentucky, 42001

  • Retina Specialty Institute

    Pensacola, Florida, 32503

  • Retinal Research Institute, LLC

    Phoenix, Arizona, 85014

  • Associated Retina Consultants

    Phoenix, Arizona, 85020

  • Retina Northwest

    Portland, Oregon, 97221

  • Oregon HSU; Casey Eye Institute

    Portland, Oregon, 97239

  • Sierra Eye Associates

    Reno, Nevada, 89502

  • Retina Assoc of Western NY

    Rochester, New York, 14620

  • Retinal Consultants Med Group

    Sacramento, California, 95825

  • Retina Associates of Utah

    Salt Lake City, Utah, 84107

  • Med Center Ophthalmology Assoc

    San Antonio, Texas, 78240

  • West Coast Retina Medical Group

    San Francisco, California, 94109

  • UCSF; Ophthalmology

    San Francisco, California, 94143

  • Orange County Retina Med Group

    Santa Ana, California, 92705

  • California Retina Consultants

    Santa Barbara, California, 93103

  • Retina Vitreous Assoc of FL

    St. Petersburg, Florida, 33711

  • Retina Associates of Florida, LLC

    Tampa, Florida, 33609

  • Retina Specialists

    Towson, Maryland, 21204

  • Wolfe Eye Clinic

    West Des Moines, Iowa, 50266

  • Vitreo-Retinal Associates, PC

    Worcester, Massachusetts, 01605

Other trials in United States

About this study

Official title: A Phase II, Multicenter, Randomized, Active Treatment-Controlled 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

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).

Being tested
Ranibizumab
Medical subject headings
Macular Degeneration

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RanibizumabDrug

    Also called Lucentis®

    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.

Study groups in NCT02510794
Study groupRoleWhat they receive
Port Delivery System with Ranibizumab 10mg/mLExperimentalParticipants 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.
Receives: Drug: Ranibizumab
Port Delivery System with Ranibizumab 40mg/mLExperimentalParticipants 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.
Receives: Drug: Ranibizumab
Port Delivery System with Ranibizumab 100mg/mLExperimentalParticipants 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.
Receives: Drug: Ranibizumab
Intravitreal Injection with Ranibizumab 0.5mgActive comparatorParticipants received ranibizumab 0.5 mg monthly ITV injections of 10 mg/mL formulation at Day 1 and every month thereafter.
Receives: Drug: Ranibizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: Baseline up to approximately 38 months

Secondary outcomes (12)

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

    Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. The minimum score possible is 0 and maximum possible is 100. A higher score represents better functioning.

    Measured: Baseline, Months 9, 10

  2. Change From Baseline in BCVA Over Time

    Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. The minimum score possible is 0 and maximum possible is 100. A higher score represents better functioning.

    Measured: Baseline up to Month 10

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

    Visual function of the study eye was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) letter score. The minimum score possible is 0 and maximum possible is 100. A higher score represents better functioning. Here, the adjusted mean from MMRM analysis is presented).

    Measured: Baseline up to Month 10

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

    Central foveal thickness (CFT) is defined as the retinal thickness in the center of the fovea

    Measured: Baseline up to Month 9

  5. Number of Implant Clogging at Month 9

    Removed implants identified as meeting serum PK criteria for possible clogging were assessed via lab-based investigation (in vitro drug release testing) to determine whether there was any implant clogging.

    Measured: Month 9

  6. Observed Maximum Serum Concentration (Cmax) of Ranibizumab

    The serum pharmacokinetics of ranibizumab were characterized by estimating Cmax between dose intervals. Estimates for these parameters were tabulated and summarized by descriptive statistics.

    Measured: Predose (0 hour) on Day 1 up to 38 months

  7. Area Under the Concentration-Time Curve From Dosing to Last Observation (AUClast) of Ranibizumab

    AUCLast is defined as area under the concentration-time curve from dosing (implant or refill) to last observation before next refill or exiting the study. The serum pharmacokinetics of ranibizumab were characterized by estimating AUC between dose intervals. Estimates for these parameters were tabulated and summarized by descriptive statistics.

    Measured: Predose (0 hour) on Day 1 up to approximately 38 months (detailed timeframe is provided in description field)

  8. Time to Maximum Concentration (Tmax) of Ranibizumab

    The serum pharmacokinetics of ranibizumab were characterized by estimating Tmax between dose intervals. Estimates for these parameters were tabulated and summarized by descriptive statistics.

    Measured: Predose (0 hour) on Day 1 up to 38 months

  9. Terminal Half-Life (t1/2) of Ranibizumab

    The serum pharmacokinetics of ranibizumab were characterized by estimating t1/2 between dose intervals. Estimates for these parameters were tabulated and summarized by descriptive statistics.

    Measured: Predose (0 hour) on Day 1 up to 38 months

  10. Observed Steady-State Serum Concentration at the End of a Dosing Interval (Ctrough) of Ranibizumab

    Measured: Predose (0 hour) on Day 1 up to 38 months

  11. Number of Participants With Ocular and Non-Ocular Adverse Events (AEs) and Serious AEs (SAEs)

    Measured: Baseline up to approximately Month 38

  12. Percentage of Participants With Positive Serum Antibodies to Ranibizumab

    Measured: Baseline up to 38 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Jul 2015 (estimated)
  2. Study start28 Sep 2015
  3. Primary completion10 Apr 2018
  4. Study completion28 Mar 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
225 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02510794
Sponsor's protocol ID
GX28228
Acronym
LADDER
Status last verified
Apr 2021
First submitted
17 Jul 2015
Last updated
6 May 2021

Publications

  • Maass KF, Maia M, Gune S, Chang MC. Pharmacodynamics of Free VEGF After Treatment with the Port Delivery Platform with Ranibizumab in Patients with Neovascular Age-Related Macular Degeneration. Ophthalmol Sci. 2026 Aug 17;6(10):101367. doi: 10.1016/j.xops.2026.101367. eCollection 2026 Oct.

    PubMed 42787488

  • 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.

    PubMed 39209113

  • Eichenbaum DA, Freeman WR, Chang MA, Brooks L, Chaudhry N, Dadgostar H, McCannel CA, Michels M, Mittra RA, Wolfe JD, Beindl VC, Jaycock P, Bobbala A, Gune S, Spicer G, Callaway N. Endophthalmitis in Eyes Treated with the Port Delivery System with Ranibizumab: Summary of Cases during Clinical Trial Development. Ophthalmol Retina. 2025 Feb;9(2):127-143. doi: 10.1016/j.oret.2024.08.005. Epub 2024 Aug 16.

    PubMed 39154860

  • 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.

    PubMed 35759124

  • 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.

    PubMed 35589078

  • 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.

    PubMed 35248647

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ranibizumab in people with Macular Degeneration, run by Genentech, Inc. at 50 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 50 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time Until a Participant First Requires the Implant Refill According to Protocol-Defined Refill Criteria (time frame: Baseline up to approximately 38 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02510794, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2021.

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