Recruiting NCT03683251

Extension Study for the Port Delivery System With Ranibizumab (Portal)

Phase III Interventional Neovascular Age-Related Macular Degeneration

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: PDS Implant with Ranibizumab 100 mg/mL.
Who it may be relevant to: Registry conditions: Neovascular Age-Related Macular Degeneration. Basic parameters: from 50 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, Argentina, Australia, Austria, Belgium +10
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

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Official title

A Multicenter, Open-Label Extension Study to Evaluate the Long-Term Safety and Tolerability of the Port Delivery System With Ranibizumab in Patients With Neovascular Age-Related Macular Degeneration (Portal)

Overview

This study will evaluate the long-term safety and tolerability of the Port Delivery System with ranibizumab (PDS) (100 mg/mL) in participants with neovascular age-related macular degeneration (nAMD) who have either completed Phase II Study GX28228 (Ladder), Phase III Study GR40548 (Archway), Phase IIIb Study WR42221 (Velodrome), or completed Week 24 visit in Study WR42221 but were not eligible to be randomized in WR42221.

Detailed description

The Transscleral Photocoagulation sub-study (sub-study 1) will evaluate the effectiveness of using transscleral photocoagulation (TPC) with the Iridex laser system to mitigate vitreous hemorrhages secondary to the Port Delivery System with ranibizumab (PDS) implantation procedure in participants with neovascular age-related macular degeneration (nAMD). The sub-study will enroll about 55 participants.

The Re-implantation sub-study (sub-study 2) will evaluate the safety of re-implantation with the updated PDS with ranibizumab . Up to 100 participants who previously participated in the main study in the United States will be enrolled and followed for a maximum of 72 weeks post-re-implantation in the substudy.

Interventions

Drug PDS Implant with Ranibizumab 100 mg/mL
Will be administered as per the schedule described in individual arm

Primary outcome measures

Incidence and Severity of Ocular and Systemic (Non-Ocular) Adverse Events (AEs) [Time frame: Baseline up to Week 240]
Incidence, Severity, and Duration of Adverse Event of Special Interest (AESIs) [Time frame: Baseline up to Week 240]
Incidence, Severity, and Duration of PDS-Associated Ocular AESIs During the Postoperative Period (Up to 37 days of Initial Implantation) and Follow-Up Period (>37 days After Implantation Surgery) for Participants who Receive the PDS Implant in the Study [Time frame: Baseline up to Week 240]
Incidence and Severity of Adverse Device Effects [Time frame: Baseline up to Week 240]
Incidence, Causality, Severity, And Duration Of Anticipated Serious Adverse Device Effects [Time frame: Baseline up to Week 240]
Sub-study 1: Rate of Vitreous Hemorrhage Secondary to Choroidal Bleeding That Does not Resolve by the Week 4 Visit After Implant Insertion Surgery. [Time frame: Baseline to Week 4]
Sub-study 2: Number of Participants with Ocular and Systemic (Non-ocular) Adverse Events (AEs) and Severity of These AEs [Time frame: Baseline to Week 72]
Sub-study 2: Number of Participants with Adverse Events of Special Interests (AESIs) and Severity of AESIs [Time frame: Baseline to Week 72]
Sub-study 2: Duration of AESIs [Time frame: Baseline to Week 72]
Sub-study 2: Number of participants with Ocular AESIs and Severity of Ocular AESIs During the Post-operative Period [Time frame: Up to Day 37 post re-implantation]

Secondary outcome measures (12)

Change in Best-Corrected Visual Acuity (BCVA) Score from Baseline Over Time, as Assessed using the ETDRS Visual Acuity Chart at a Starting Distance of 4 Meters [Time frame: Baseline up to Week 240]
Percentage of Participants who Lose <15, <10, or <5 Letters in BCVA Score from Baseline Over Time [Time frame: Baseline up to Week 240]
Percentage of Participants with BCVA Score of 38 Letters (of 20/200 Approximate Snellen Equivalent) or Worse over Time [Time frame: Baseline up to Week 240]
Percentage of Participants with BCVA Score of 69 Letters (20/40 Approximate Snellen Equivalent) or Better over Time [Time frame: Baseline up to Week 240]
Change from Baseline in Center Point Thickness (CPT) Over Time [Time frame: Baseline up to Week 240]
Percentage of Participants who Undergo Supplemental Treatment with Intravitreal Ranibizumab 0.5 mg During Each Refill-exchange Interval [Time frame: Baseline up to Week 240]
Sub-study 1: Incidence of Ocular Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) in the Study eye [Time frame: Baseline up to Week 104]
Sub-study 1: Incidence of AEs Commonly Seen After Transscleral Cyclophotocoagulation (TS-CPC) for Treatment of Glaucoma in the Study eye [Time frame: Baseline up to Week 104]
Sub-study 1: Time From Surgery to Vitreous Hemorrhage Resolution in the Study eye [Time frame: Baseline up to Week 104]
Sub-study 1: Incidence of Vitreous Hemorrhage Grade 3 and Higher in the Study eye over time [Time frame: Baseline up to Week 104]
Sub-study 1: Distribution of Vitreous Hemorrhage Grade in the Study eye Over Time [Time frame: Baseline up to Week 104]
Sub-study 1: Rate of Vitrectomy in the Study eye [Time frame: Baseline up to Week 104]

Eligibility criteria

Inclusion criteria

Previous enrollment in and completion of Study GX28228 (Ladder) or Study GR40548 (Archway), without early treatment or study discontinuation in either study OR Previous enrollment in Study WR42221 (Velodrome) and either not eligible to be randomized in Study WR42221 at Week 24 or completed the study (from the Q24W or Q36W arm)
Ability and willingness to undertake all scheduled visits and assessments
For women of childbearing potential: agreement to remain abstinent or use contraceptive measures

Exclusion criteria

Pregnant or breastfeeding, or intending to become pregnant during the treatment period and for at least 28 days after the last intravitreal injection of ranibizumab or 1 year after the last Implant refill-exchange of ranibizumab
History of other ocular diseases that give reasonable suspicion of a disease or condition that contraindicates the use of ranibizumab, that might affect interpretation of the results of the study or that renders the participant at high risk for treatment complications
History of other diseases, metabolic dysfunction, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of ranibizumab or placement of the Implant and that might affect interpretation of the results of the study or that renders the participant at high risk of treatment complications
Requirement for continuous use of any medications or treatments indicated in the "Prohibited Therapy"

Sub-study 1

Inclusion criteria

\- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures

Participants must meet the following ocular criteria for the study eye for substudy entry:

Diagnosis of exudative nAMD within 2 years prior to the enrollment visit
Previous treatment with at least two anti-VEGF ITV injections (e.g., ranibizumab, bevacizumab, or aflibercept) for nAMD per standard of care within 6 months prior to the enrollment visit
Demonstrated response to prior anti-VEGF ITV treatment since diagnosis, as evidenced at enrollment by the following:

Overall decrease in nAMD disease activity detected on SD-OCT AND Stable or improved best-corrected visual acuity (BCVA)

All subtypes of nAMD lesions are permissible (i.e., type I, type II, type III, or mixed forms per optical coherence tomography (OCT) classification) nAMD lesions at the time of diagnosis must involve the macula (6 mm diameter centered at the fovea).
Sufficiently clear ocular media and adequate pupillary dilation to allow for analysis and grading by the central reading center of FP and SD-OCT images.

Exclusion Criteria Prior Ocular Treatments Study Eye

History of vitrectomy surgery, submacular surgery, or other surgical intervention for AMD
Prior treatment with Visudyne, external-beam radiation therapy, or transpupillary thermotherapy
Previous treatment with corticosteroid ITV injection
Previous intraocular device implantation
Previous laser (any type) used for AMD treatment

Either Eye

Treatment with anti-VEGF agents other than ranibizumab within 1 month prior to the enrollment visit
Prior participation in a clinical trial involving anti-VEGF drugs within 6 months prior to the enrollment visit, other than ranibizumab

CNV Lesion Charateristics Study Eye

Subretinal hemorrhage that involves the center of the fovea, if the hemorrhage is greater than 0.5 disc area (1.27 mm2 ) in size at screening
Subfoveal fibrosis or subfoveal atrophy

Either Eye

\- CNV due to other causes, such as ocular histoplasmosis, trauma, or pathologic myopia

Concurrent Ocular Conditions Study Eye

Retinal pigment epithelial tear
Any concurrent intraocular condition (e.g., cataract, glaucoma, diabetic retinopathy, or epiretinal membrane) that would either require surgical intervention during the study to prevent or treat visual loss that might result from that condition or affect interpretation of study results
Active intraocular inflammation (grade trace or above)
History of vitreous hemorrhage
History of rhegmatogenous retinal detachment
History of rhegmatogenous retinal tears or peripheral retinal breaks within 3 months prior to the enrollment visit
Aphakia or absence of the posterior capsule
Previous violation of the posterior capsule is also an exclusion criterion unless it occurred as a result of yttrium-aluminum garnet (YAG) laser posterior capsulotomy in association with prior, posterior chamber intraocular lens implantation.
Spherical equivalent of the refractive error demonstrating more than 8 diopters of myopia
Preoperative refractive error that exceeds 8 diopters of myopia, for participants who have undergone prior refractive or cataract surgery in the study eye
Intraocular surgery (including cataract surgery) within 3 months preceding the enrollment visit
Uncontrolled ocular hypertension or glaucoma and any such condition the investigator determines may require a glaucoma-filtering surgery during a patient's participation in the study
History of glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery
History of corneal transplant
History of prior vitrectomy surgery and absence of posterior capsule

Either Eye

History of idiopathic or autoimmune-associated uveitis
Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis

Concurrent Systemic Conditions

Inability to comply with study schedule or procedures as described in the study protocol
Uncontrolled blood pressure
History of stroke within the last 3 months prior to informed consent
Uncontrolled atrial fibrillation within 3 months of informed consent
History of myocardial infarction within the last 3 months prior to informed consent
History of other disease, metabolic dysfunction, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of ranibizumab or placement of the implant and that might affect interpretation of the results of the study or renders the patient at high risk of treatment complications in the opinion of the investigator
Current systemic treatment for a confirmed active systemic infection
Use of any systemic anti-VEGF agents
Chronic use of oral corticosteroids
Active cancer within 12 months of enrollment
Previous participation in any non-ocular (systemic) disease studies of investigational drugs within 1 month preceding the informed consent (excluding vitamins and minerals)
Use of antimitotic or antimetabolite therapy within 30 days or 5 elimination half-lives of the enrollment visit
History of albinism
Pregnant or breastfeeding, or intending to become pregnant during the treatment period and for at least 28 days after the last ITV injection of ranibizumab or 1 year after the last implant refill-exchange of ranibizumab

Sub-study 2

Inclusion criteria

Having experienced septum dislodgement in the original implant while in the main study or after exiting the main study Ocular Inclusion Criteria for Study Eye
Sufficiently clear ocular media and adequate pupillary dilation to allow for analysis and grading by central reading center

Exclusion Criteria (Cohort 1 only):

Concurrent Ocular Conditions-Study Eye

Any ocular condition that may render the patient at high risk for surgical or treatment complications
Intraocular surgery (including cataract surgery) within 1 month preceding the enrollment visit
Any use of medicated intraocular implants (other than the PDS implant), at any time prior to enrollment
History of rhegmatogenous retinal tears or peripheral retinal breaks within 3 months prior to the enrollment visit
Any concurrent ocular condition that would require surgical intervention during the study to prevent or treat visual loss
Concurrent conjunctival, Tenon's capsule, and/or scleral condition in the supero-temporal quadrant of the eye (e.g., scarring, thinning, mass) that may affect the refill-exchange procedure of the PDS implant
Ongoing ocular complications that might affect participant safety

Concurrent Ocular Conditions-Either Eye

Suspected or active ocular or periocular infection
Any history of uveitis
Active blepharitis

Concurrent Systemic Conditions

Recent history (in the last 3 months prior to enrollment) of other disease, other non-diabetic metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a condition that contraindicates the use of ranibizumab or surgical placement of the PDS implant; that might affect interpretation of the results of the study; or that renders the participant at high risk for treatment complications
Active cancer within the last 12 months, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or prostate cancer
Current systemic treatment for a confirmed active systemic infection - Participation in an investigational trial that involves treatment with any drug or device (with the exception of vitamins and minerals or enrollment in the main study GR40549) within 6 months prior to enrollment.
Use of antimitotic or antimetabolite therapy within 30 days or 5 elimination half-lives.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: Non-randomized
Model: Parallel assignment
Masking: Single blind
Primary purpose: Treatment