A Study Of The Efficacy And Safety Of The Port Delivery System With Ranibizumab In Patients With Neovascular Age-Related Macular Degeneration Previously Treated With Intravitreal Agents Other Than Ranibizumab

• Status: Not yet recruiting
• Trial end date: 2023-08-21
• Target enrollment: 0
• Participant gender: All

Summary

Study ML43000 is a Phase IIIb/IV multicenter, open-label (visual assessor-masked) study designed to assess the efficacy and safety of PDS 100 mg/mL Q24W in patients with nAMD who have been previously treated with anti-VEGF agents other than ranibizumab. Approximately 200 patients will be enrolled at approximately 40 sites.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Genentech, Inc.
• Treatments: Ranibizumab

Criteria

Inclusion Criteria:

Ocular Inclusion Criteria

• Initial diagnosis of nAMD within 6 to 18 months prior to the signing of the ICF

• Previous treatment with at least 3 anti-VEGF injections other than ranibizumab for nAMD per standard of care in the 9 months prior to PDS implantation; the most recent anti-VEGF injection must have occurred within 12 weeks of PDS implantation

• The last 2 anti-VEGF injections for nAMD prior to PDS implantation must be with the same eligible anti-VEGF agent, either bevacizumab or aflibercept

• Availability of historical visual acuity data and SD-OCT imaging prior to the first anti-VEGF treatment for nAMD until the time of study enrollment

• Availability of comprehensive historical anti-VEGF injection data including anti-VEGF agent administered and date of administration from the first anti-VEGF treatment for nAMD until the time of study enrollment

• Demonstrated response to prior anti-VEGF intravitreal treatment since diagnosis BCVA of 34 letters (approximate 20/200 Snellen equivalent) or better, using ETDRS chart at a starting distance of 4 meters (see the BCVA manual for additional details) at screening and enrollment visits

• All subtypes of nAMD lesions are permissible

• 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 clinical exam and analysis and grading by the central reading center of SD-OCT images

Exclusion Criteria:

Study Eye

• Prior vitrectomy surgery, submacular surgery, or other surgical intervention for AMD

• Prior pars plana vitrectomy surgery

• Prior treatment with ranibizumab

• Prior treatment with verteporfin for injection, external-beam radiation therapy, or transpupillary thermotherapy

• Previous treatment with corticosteroid intravitreal injection

• Previous intraocular device implantation excluding intraocular lenses

• Previous intraocular surgery (including cataract surgery) within 3 months of study enrollment

• Previous laser (any type) used for AMD treatment

• History of vitreous hemorrhage

• History of rhegmatogenous retinal detachment

• History of glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery

• History of corneal transplant

• History of conjunctival surgery in the superotemporal quadrant

• Prior participation in a clinical trial involving any intravitreal anti-VEGF agents

• Subretinal hemorrhage that involves the center of the fovea

• Subfoveal fibrosis or subfoveal atrophy 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

• Rhegmatogenous retinal tears or peripheral retinal breaks on depressed fundus exam that are untreated, or treated within the 3 months prior to study enrollment

• 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 or evidence of pathologic myopia on depressed fundus examination

• Preoperative refractive error that exceeds 8 diopters of myopia, for patients who have undergone prior refractive or cataract surgery

• Spherical equivalent of the refractive error demonstrating more than 5 diopters of hyperopia

• Preoperative refractive error that exceeds 5 diopters of hyperopia, for patients who have undergone prior refractive or cataract surgery

• Uncontrolled ocular hypertension or glaucoma

• Scleral pathology in the superotemporal quadrant

• Conjunctival pathologies in the superotemporal quadrant

• History or presence of severe posterior blepharitis, recurrent chalazia or hordeolum, severe dry eye syndrome, or severe allergic conjunctivitis

• Ectropion, entropion or other impairment of the upper or lower eyelid impacting lid functionality needed to protect the ocular surface from exposure

• Trichiasis

• Corneal neuropathy

• Lagophthalmos or incomplete blink

• Active or history of facial nerve palsy/paresis

Either Eye

• Prior treatment with brolucizumab (at any time prior to screening visit)

• Prior treatment with any anti-VEGF biosimilar agents (at any time prior to screening visit)

• Prior treatment with external-beam radiation therapy or brachytherapy

• MNV due to causes such as ocular histoplasmosis, trauma, or pathologic myopia

• MNV due to other causes, such as ocular histoplasmosis, trauma, or pathologic myopia MNV masquerading lesions (e.g., cone dystrophy, adult vitelliform dystrophy, pattern dystrophy)

• Any active or history of uveitis (e.g., idiopathic, drug-associated or autoimmune-associated)

• Active or history of keratitis, scleritis, or endophthalmitis

• Suspected or active ocular or periocular infectious conjunctivitis or endophthalmitis

• Active or history of Sjogrens syndrome or keratoconjunctivitis sicca

• Active or history of floppy eyelid syndrome

• Active or history of chronic eye rubbing

• Active thyroid eye disease

Concurrent Systemic Conditions:

• Uncontrolled blood pressure

• Active or history of autoimmune diseases

• 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 active systemic infection

• Use of any systemic anti-VEGF agents

• Chronic use of oral corticosteroids

• Active cancer within 12 months of enrollment except

• Previous participation in any non-ocular (systemic) disease studies of investigational drugs within 1 month preceding the informed consent

• Use of antimitotic or antimetabolite therapy within 30 days or 5 elimination half-lives of the enrollment visit

• Pregnant or breastfeeding