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

PHASE3RECRUITING

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.

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Study details:

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.

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

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
  • 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.
  • 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

  • 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'
  • 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
  • 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
  • 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
  • CNV due to other causes, such as ocular histoplasmosis, trauma, or pathologic myopia
  • 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
  • History of idiopathic or autoimmune-associated uveitis
  • Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis
  • 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
  • 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
  • Suspected or active ocular or periocular infection
  • Any history of uveitis
  • Active blepharitis
  • 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.
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    Eligibility

    Age eligible for study : 50 and older

    Healthy volunteers accepted : No

    Gender eligible for study: All

    Things to know

    Study dates

    Study start: 2018-09-20

    Primary completion: 2029-09-30

    Study completion finish: 2029-09-30

    study type

    Study type

    TREATMENT

    phase

    Phase

      PHASE3

    trial

    Trial ID

    NCT03683251

    Intervention or treatment

    DRUG: PDS Implant with Ranibizumab 100 mg/mL

    Conditions

    • • Neovascular Age-Related Macular Degeneration
    Image related to Neovascular Age-Related Macular Degeneration

    • Condition: Neovascular Age-Related Macular Degeneration

    • DRUG: PDS Implant with Ranibizumab 100 mg/mL

    • Albury, New South Wales, Australia and more

    • Sponsor: Hoffmann-La Roche

    You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.

    Are you running this trial? If you're a clinic or sponsor, you can claim this study. Claim or learn more.

    Find a site

    Closest Location:

    Eyeclinic Albury Wodonga

    Research sites nearby

    Select from list below to view details:

    • Eyeclinic Albury Wodonga

      Albury, New South Wales, Australia

    • Eye and Retina Consultants

      Hurstville, New South Wales, Australia

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    Study Plan

    This section provides details of the study plan, including how the study is designed and what the study is measuring.

    How is the study designed?

    Participant Group/ArmIntervention/Treatment
    EXPERIMENTAL: PDS Implant Cohort 1 (US only)
    • Participants with PDS implant from Study GX28228 treated with refill-exchanges of 100 mg/mL ranibizumab Q24W. Participants will switch to an every 12 weeks (Q12W) visit schedule from Week 168 to Week 240.
    • Eligible participants from Study GX28228 will be enrolled upon completion of their final visit.
    DRUG: PDS Implant with Ranibizumab 100 mg/mL
    • Will be administered as per the schedule described in individual arm
    EXPERIMENTAL: PDS Implant Cohort 2 (US only)
    • Participants with PDS implant from Study GR40548 treated with refill-exchanges of 100 mg/mL ranibizumab Q24W. Participants will switch to an every 12 weeks (Q12W) visit schedule from Week 144 to Week 240.
    • Eligible participants from Study GR40548 will be enrolled upon completion of their final visit.
    DRUG: PDS Implant with Ranibizumab 100 mg/mL
    • Will be administered as per the schedule described in individual arm
    EXPERIMENTAL: PDS Implant Cohort 3 (US only)
    • Participants in the intravitreal ranibizumab arm of Study GX28228 who will receive the PDS implant upon study entry and refill-exchanges of 100 mg/mL ranibizumab Q24W. Participants will switch to an every 12 weeks (Q12W) visit schedule from Week 168 to Week 240.
    • Eligible participants from Study GX28228 will be enrolled upon completion of their final visit.
    DRUG: PDS Implant with Ranibizumab 100 mg/mL
    • Will be administered as per the schedule described in individual arm
    EXPERIMENTAL: PDS Implant Cohort 4 (US only)
    • Participants in the intravitreal ranibizumab arm of Study GR40548 who will receive the PDS implant upon study entry and refill-exchanges of 100 mg/mL ranibizumab Q24W. Participants will switch to an every 12 weeks (Q12W) visit schedule from Week 144 to Week 240.
    • Eligible participants from Study GR40548 will be enrolled upon completion of their final visit.
    DRUG: PDS Implant with Ranibizumab 100 mg/mL
    • Will be administered as per the schedule described in individual arm
    EXPERIMENTAL: PDS Implant Cohort 5 (ex-US only)
    • Participants from Study WR42221 who completed Week 24 but were not eligible to be randomized within WR42221 and who will be treated with refill-exchanges of ranibizumab 100 mg/mL Q24W
    DRUG: PDS Implant with Ranibizumab 100 mg/mL
    • Will be administered as per the schedule described in individual arm
    EXPERIMENTAL: PDS Implant Cohort 6 (ex-US only)
    • Participants from Study WR42221 randomized to the Q24W arm, who will continue to be treated with refill-exchanges of ranibizumab 100 mg/mL Q24W
    DRUG: PDS Implant with Ranibizumab 100 mg/mL
    • Will be administered as per the schedule described in individual arm
    EXPERIMENTAL: PDS Implant Cohort 7 (ex-US only)
    • Participants from Study WR42221 randomized to the Q36W arm, who will continue to be treated with refill-exchanges of ranibizumab 100 mg/mL Q36W
    DRUG: PDS Implant with Ranibizumab 100 mg/mL
    • Will be administered as per the schedule described in individual arm
    EXPERIMENTAL: Sub-study 1: PDS Implant
    • Participants will receive PDS implant using TPC on Day 1 followed by refill-exchanges of ranibizumab 100 mg/mL via the PDS Q24W.
    DRUG: PDS Implant with Ranibizumab 100 mg/mL
    • Will be administered as per the schedule described in individual arm
    EXPERIMENTAL: Sub-study 2: Cohort 1
    • Participants will undergo re-implantation with the updated PDS implant and receive 2 refill-exchanges of ranibizumab 100 mg/mL Q24W
    DRUG: PDS Implant with Ranibizumab 100 mg/mL
    • Will be administered as per the schedule described in individual arm
    EXPERIMENTAL: Sub-study 2: Cohort 2a
    • Participants who received an updated PDS implant, have \< 24 weeks post-re-implantation follow-up and no refill exchange visit in the main study, will undergo two refill-exchange procedures with ranibizumab 100 mg/mL Q24W post main study re-implantation visit.
    DRUG: PDS Implant with Ranibizumab 100 mg/mL
    • Will be administered as per the schedule described in individual arm
    EXPERIMENTAL: Sub-study 2: Cohort 2b
    • Participants who received an updated PDS implant, have \< 48 weeks post-re-implantation follow-up and one refill exchange visit in the main study, will undergo one refill-exchange procedure with ranibizumab 100 mg/mL Q24W post main study re-implantation visit.
    DRUG: PDS Implant with Ranibizumab 100 mg/mL
    • Will be administered as per the schedule described in individual arm

    What is the study measuring?

    Primary outcome

    Primary Outcome MeasurePrimary Outcome DescriptionPrimary Outcome Time Frame
    Incidence and Severity of Ocular and Systemic (Non-Ocular) Adverse Events (AEs)Not SpecifiedBaseline up to Week 240
    Incidence, Severity, and Duration of Adverse Event of Special Interest (AESIs)Not SpecifiedBaseline 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 StudyNot SpecifiedBaseline up to Week 240
    Incidence and Severity of Adverse Device EffectsNot SpecifiedBaseline up to Week 240
    Incidence, Causality, Severity, And Duration Of Anticipated Serious Adverse Device EffectsNot SpecifiedBaseline 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.Not SpecifiedBaseline to Week 4
    Sub-study 2: Number of Participants with Ocular and Systemic (Non-ocular) Adverse Events (AEs) and Severity of These AEsNot SpecifiedBaseline to Week 72
    Sub-study 2: Number of Participants with Adverse Events of Special Interests (AESIs) and Severity of AESIsNot SpecifiedBaseline to Week 72
    Sub-study 2: Duration of AESIsNot SpecifiedBaseline to Week 72
    Sub-study 2: Number of participants with Ocular AESIs and Severity of Ocular AESIs During the Post-operative PeriodNot SpecifiedUp to Day 37 post re-implantation
    Sub-study 2: Number of participants with Ocular AESIs and Severity of Ocular AESIs During the Follow-up PeriodNot Specified> 37 days post re-implantation (up to approximately Week 72)
    Sub-study 2: Duration of Ocular AESIs During the Post-operative PeriodNot SpecifiedUp to Day 37 post re-implantation
    Sub-study 2: Duration of Ocular AESIs During the Follow-up PeriodNot Specified> 37 days post re-implantation (up to approximately Week 72)
    Sub-study 2: Number of Participants with Adverse Device Effects (ADEs) and Severity of ADEsNot SpecifiedBaseline to Week 72
    Sub-study 2: Number of Participants with Anticipated Serious ADEs and Severity of Anticipated Serious ADEsNot SpecifiedBaseline to Week 72
    Sub-study 2: Duration of Anticipated Serious ADEsNot SpecifiedBaseline to Week 72
    Sub-study 2: Number of Device DeficienciesNot SpecifiedBaseline to Week 72

    Secondary outcome

    Secondary Outcome MeasureSecondary Outcome DescriptionSecondary Outcome Time Frame
    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 MetersETDRS = Early Treatment Diabetic Retinopathy Study A vision score of 20/20 vision is considered normal. A score of 20/200 is considered being legally blind.Baseline up to Week 240
    Percentage of Participants who Lose <15, <10, or <5 Letters in BCVA Score from Baseline Over TimeNot SpecifiedBaseline up to Week 240
    Percentage of Participants with BCVA Score of 38 Letters (of 20/200 Approximate Snellen Equivalent) or Worse over TimeNot SpecifiedBaseline up to Week 240
    Percentage of Participants with BCVA Score of 69 Letters (20/40 Approximate Snellen Equivalent) or Better over TimeNot SpecifiedBaseline up to Week 240
    Change from Baseline in Center Point Thickness (CPT) Over TimeNot SpecifiedBaseline up to Week 240
    Percentage of Participants who Undergo Supplemental Treatment with Intravitreal Ranibizumab 0.5 mg During Each Refill-exchange IntervalNot SpecifiedBaseline up to Week 240
    Sub-study 1: Incidence of Ocular Adverse Events (AEs) and Adverse Events of Special Interest (AESIs) in the Study eyeNot SpecifiedBaseline up to Week 104
    Sub-study 1: Incidence of AEs Commonly Seen After Transscleral Cyclophotocoagulation (TS-CPC) for Treatment of Glaucoma in the Study eyeNot SpecifiedBaseline up to Week 104
    Sub-study 1: Time From Surgery to Vitreous Hemorrhage Resolution in the Study eyeNot SpecifiedBaseline up to Week 104
    Sub-study 1: Incidence of Vitreous Hemorrhage Grade 3 and Higher in the Study eye over timeNot SpecifiedBaseline up to Week 104
    Sub-study 1: Distribution of Vitreous Hemorrhage Grade in the Study eye Over TimeNot SpecifiedBaseline up to Week 104
    Sub-study 1: Rate of Vitrectomy in the Study eyeNot SpecifiedBaseline up to Week 104
    Sub-study 1: Percentage of Participants who Lose <15, <10, or <5 Letters in BCVA Score From Baseline Over TimeNot SpecifiedBaseline up to Week 104
    Sub-study 1: Change in BCVA Score From Baseline Over TimeNot SpecifiedBaseline up to Week 104
    Sub-study 1: Change from Baseline in CPT Over TimeNot SpecifiedBaseline up to Week 104
    Sub-study 1: Change From Baseline in Center Subfield Thickness (CST) Over TimeNot SpecifiedBaseline up to Week 104
    Sub-study 2: Number of Participants with Ocular AESIs and Severity of AESIs Following Refill-exchangeNot SpecifiedUp to approximately Week 72
    Sub-study 2: Duration of AESIs Following Refill-exchangeNot SpecifiedUp to approximately Week 72
    Sub-study 2: Number of Participants With ADEs and Severity of ADEs Following Refill-exchangeNot SpecifiedUp to approximately Week 72
    Sub-study 2: Number of Participants with Anticipated Serious ADEs and Severity of Anticipated Serious ADEs Following Refill-exchangeNot SpecifiedUp to approximately Week 72
    Sub-study 2: Number of Device Deficiencies Following Refill-exchangeNot SpecifiedUp to approximately Week 72

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    References

    Clinical Trials Gov: Extension Study for the Port Delivery System With Ranibizumab (Portal)

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