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Belvedere: A Study Of The Response to Treatment After Transition to The Port Delivery System With Ranibizumab [Susvimo (Ranibizumab Injection)] In Patients With Neovascular Age-Related Macular Degeneration Previously Treated With Intravitreal Agents Other Than Ranibizumab

Sponsor
Genentech, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04853251
Collaborator
(none)
200
Enrollment
33
Locations
1
Arm
25.6
Anticipated Duration (Months)
6.1
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Study ML43000 is a Phase IV multicenter, open-label (BCVA assessor-masked) study designed to assess the response to treatment with SUSVIMO Q24W in patients with nAMD who have been previously treated with anti-VEGF agents other than ranibizumab. The substudy will evaluate the impact on corneal endothelial cells with SUSVIMO refilled every 24 weeks (Q24W) in patients with neovascular age-related macular degeneration (nAMD).

Condition or Disease Intervention/Treatment Phase
  • Device: SUSVIMO (ranibizumab injection)
  • Drug: LUCENTIS (ranibizumab injection)
 Phase 4

Study Design

Study Type:
Interventional
Anticipated Enrollment :
200 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase IV, Multicenter, Open-Label, Single-Arm Study Of The Response to Treatment After Transition to The Port Delivery System With Ranibizumab [Susvimo (Ranibizumab Injection)] In Patients With Neovascular Age-Related Macular Degeneration Previously Treated With Intravitreal Agents Other Than Ranibizumab
Actual Study Start Date :
Dec 14, 2021
Anticipated Primary Completion Date :
Jan 31, 2024
Anticipated Study Completion Date :
Jan 31, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: SUSVIMO

Participants will have the implant (filled prior to implantation with approximately 20 uL of the 100-mg/mL formulation of ranibizumab [approximately 2-mg dose of ranibizumab]) surgically inserted in the study eye at the Day 1 visit following their enrollment visit. After the initial fill of the implant with ranibizumab, patients will receive implant refill-exchanges at fixed 24-week intervals.

Device: SUSVIMO (ranibizumab injection)
The ranibizumab 100 mg/mL will be administered to participants via the SUSVIMO Ocular Implant (IMP)

Drug: LUCENTIS (ranibizumab injection)
Ranibizumab (intravitreal 0.5-mg injections of 10 mg/mL formulation) will be used in the study eye as supplemental treatment. If a study patient discontinues study treatment, he/she may start receiving intravitreal ranibizumab injections in the study eye, per investigator's discretion.

Outcome Measures

Primary Outcome Measures

  1. Mean change from baseline in Best Corrected Visual Acuity (BCVA) letter score at Week 40, as assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart at a starting distance of 4 meters [Baseline up to Week 40]

    PDS 100 mg/mL Q24W in nAMD particpants previously treated with intravitreal anti-VEGF agents other than ranibizumab

  2. Substudy: Change in corneal endothelial cell density (ECD) from baseline at Week 48 in the study eye as compared with the fellow eye, as assessed by specular microscopy [Baseline up to Week 48]

Secondary Outcome Measures

  1. Mean change from baseline in BCVA letter score at Week 40, as assessed using the ETDRS visual acuity chart at a starting distance of 4 meters [Baseline up to Week 40]

    PDS 100 mg/mL Q24W in participants with nAMD by subgroup as defined by the last two consecutive anti-VEGF agent administered to the study eye prior to Day 1, aflibercept or bevacizumab

  2. Percentage of participants with BCVA score of 69 letters (approximate 20/40 Snellen equivalent) or better at each scheduled visit over time to Week 52 [Baseline up to Week 52]

  3. Percentage of participants who lose < 15, < 10, < 5, or gain ≥ 0, > 0, ≥ 5, ≥ 10, or ≥15 letters in BCVA score from enrollment at each scheduled visit over time to Week 52 [Baseline up to Week 52]

  4. Annualized rate of ranibizumab treatments during the study compared with annualized rate of intravitreal anti-VEGF treatments prior to screening [Baseline up to approximately 12 months]

  5. Mean change in center point thickness (CPT) from baseline on spectral-domain optical coherence tomography (SD-OCT) at each scheduled visit over time to Week 52 [Baseline up to Week 52]

  6. Percentage of participants who do not require supplemental treatment with intravitreal LUCENTIS (ranibizumab injection) 0.5 mg prior to protocol-specified refill-exchanges [Day 1 to Week 48]

  7. Percentage of participants with and without subretinal (SRF) and/or intraretinal fluid (IRF) on SD-OCT at enrollment and over study duration [Baseline up to approximately Week 52]

  8. Percentage of participants with ocular serious adverse events (SAEs) [Day 1 up to approximately Week 52]

  9. Percentage of participants with ocular adverse events of special interest (AESIs) [Day 1 to Week 52]

  10. Percentage of participants with adverse device effects (ADEs) in the course of the study [Day 1 to Week 52]

  11. Percentage of participants with ocular AESIs during the postoperative period [Baseline up to 37 days of initial implantation]

  12. Percentage of participants with ocular AESIs during the intermediate postoperative period [38 to 93 days after implantation]

  13. Percentage of participants with ocular AESIs during the follow-up period [Week 52]

    The investigator will follow each adverse event until the event has resolved to baseline grade or better, the event is assessed as stable by the investigator, the patient is lost to follow-up, or the patient withdraws consent.

  14. Change in corneal ECD from baseline at Week 24 in the study eye as compared with the fellow eye [Baseline up to Week 24]

  15. Change in the coefficient of variation (CV) of corneal endothelial cell area (standard deviation of the cell area/mean cell area) from baseline at Weeks 24 and 48 in the study eye as compared with the fellow eye [Baseline, Week 24, Week 48]

  16. Change in percentage of hexagonal endothelial cells [Baseline, Week 24, Week 48]

Eligibility Criteria

Criteria

Ages Eligible for Study:
50 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No

Inclusion Criteria

Ocular Inclusion Criteria

  • Initial diagnosis of nAMD within 6 to 18 months prior to screening

  • Previous treatment with at least 3 anti-VEGF injections other than ranibizumab for nAMD per standard of care within 9 months prior to Day 1 (SUSVIMO 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 screening must be with either bevacizumab or aflibercept

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

  • 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

  • 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 at screening and enrollment

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

Substudy Inclusion Criteria

General Inclusion Criteria General inclusion criteria for this substudy are consistent with the inclusion criteria of the parent study ML43000. In addition, a signed Informed Consent for this substudy is required for participation.

Exclusion Criteria

Prior Ocular Treatment 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 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

Fellow (Non-Study) Eye

• Previous PDS implantation

Either Eye

  • Previous intraocular surgery (including cataract surgery) within 6 months of study enrollment

  • Prior treatment with brolucizumab

  • Prior treatment with any anti-VEGF biosimilar agents

  • Prior treatment with external-beam radiation therapy or brachytherapy

MNV (CNV) Lesion Characteristics

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

  • 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)

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

  • 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 exam

  • 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 (e.g., scleral thinning or calcification)

  • 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

Fellow (Non-Study) Eye

  • Concurrent intraocular condition that would require surgical intervention during the study (e.g., cataract, glaucoma surgery)

  • Concurrent PDS implantation

Either Eye

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

  • Active or history of keratitis, scleritis, or endophthalmitis

  • Active ocular or periocular infection (i.e. conjunctivitis, dacryocystitis etc.)

  • 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 such as rheumatoid arthritis, lupus, granulomatosis with polyangiitis (Wegner's), etc.

  • History of stroke within the last 3 months prior to screening

  • Uncontrolled atrial fibrillation within 3 months of screening

  • History of myocardial infarction within the last 3 months prior to screening

  • 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 for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, and prostate cancer with a Gleason score of ≤ 6 and a stable prostate-specific antigen for > 12 months

  • Previous participation in any non-ocular (systemic) disease studies of investigational drugs within 1 month prior to screening (excluding vitamins and minerals)

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

  • Pregnant or breastfeeding, or intention to become pregnant during the study

  • Women of childbearing potential, must have a negative urine pregnancy test result within 28 days prior to initiation of study treatment. If the urine pregnancy test is positive, it must be confirmed by a serum pregnancy test.

Substudy Exclusion Criteria

Exclusion criteria for this substudy are consistent with the exclusion criteria of the parent Study ML43000

Fellow (Non-Study) Eye

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

  • Prior pars plana vitrectomy surgery

  • Previous intraocular device implantation excluding intraocular lenses

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

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

Either Eye

  • Intraocular laser therapy including selective laser trabeculoplasty, yttrium-aluminum garnet (YAG), prophylactic peripheral iridotomy within 1 year of screening, or YAG capsulotomy within 3 months of screening

  • Contact lens wear in either eye within 2 months of screening

  • Any prior ocular trauma (blunt or penetrating)

  • History of corneal transplantation, including partial-thickness corneal grafts (e.g., Descemet membrane endothelial keratoplasty, Descemet stripping endothelial keratoplasty)

Concurrent Ocular Conditions

Fellow Eye

• Aphakia or absence of the posterior pole

Either Eye

  • Corneal ECD < 1500 cells/mm2 in either eye at screening as determined by the independent reading center

  • Fuchs endothelial corneal dystrophy Grade ≥ 2

  • Previous corneal endothelial cell damage, including from blunt or surgical trauma (including complicated cataract surgery resulting in complicated lens placement such as anterior chamber intraocular lens, sulcus intraocular lens, aphakia, etc.)

  • Any ocular condition that precludes obtaining an analyzable specular microscopy image

  • Active or history of corneal edema

  • Active or history of corneal dystrophies

  • Active or history of iridocorneal endothelial syndrome

  • Active or history of pseudoexfoliation syndrome

  • Active or history of herpetic keratitis or kerato-uveitis (including herpes simplex virus and herpes zoster virus)

Contacts and Locations

Locations

Site City State Country Postal Code
1 Barnet Dulaney Perkins Eye Center Mesa Arizona United States 85206
2 Arizona Retina and Vitreous Consultants Phoenix Arizona United States 85021
3 California Eye Specialists Medical group Inc. Pasadena California United States 91107
4 Retinal Consultants Med Group Sacramento California United States 95825
5 Orange County Retina Med Group Santa Ana California United States 92705
6 Southwest Retina Consultants Durango Colorado United States 81303
7 Retina Group of New England Waterford Connecticut United States 06385
8 Ft Lauderdale Eye Institute Miami Lakes Florida United States 33016
9 Retina Specialty Institute Pensacola Florida United States 32503
10 Retina Vitreous Associates of Florida Saint Petersburg Florida United States 33711-1141
11 Southeast Retina Center Augusta Georgia United States 30909
12 University Retina and Macula Associates, PC Lemont Illinois United States 60439
13 Wolfe Eye Clinic West Des Moines Iowa United States 50266
14 The Retina Care Center Baltimore Maryland United States 21209
15 Wilmer Eye Institute Johns Hopkins University Baltimore Maryland United States 21287-0005
16 Retina Group of Washington Chevy Chase Maryland United States 20815
17 Cumberland Valley Retina Consultants Hagerstown Maryland United States 21740
18 Associated Retinal Consultants PC Royal Oak Michigan United States 48073
19 VitreoRetinal Surgery, PLLC.; DBA Retina Consultants of Minnesota Edina Minnesota United States 55435
20 Midwest Vision Research Foundation Chesterfield Missouri United States 63017
21 Sierra Eye Associates Reno Nevada United States 89502
22 Western Carolina Retinal Associate PA Asheville North Carolina United States 28803
23 Cincinnati Eye Institute Cincinnati Ohio United States 45242
24 Mid Atlantic Retina Philadelphia Pennsylvania United States 19107
25 Palmetto Retina Center Florence South Carolina United States 29501
26 Palmetto Retina Center, LLC West Columbia South Carolina United States 29169
27 Tennessee Retina PC Nashville Tennessee United States 37203
28 Austin Retina Associates Austin Texas United States 78705
29 Retina Consultants of Texas Bellaire Texas United States 77401
30 Retina Associates of Utah Salt Lake City Utah United States 84107
31 Piedmont Eye Center Lynchburg Virginia United States 24502
32 Wagner Macula & Retina Center Norfolk Virginia United States 23502
33 Retina Institute of Virginia Richmond Virginia United States 23235

Sponsors and Collaborators

  • Genentech, Inc.

Investigators

  • Study Director: Clinical Trials, Genetech

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT04853251
Other Study ID Numbers:
  • ML43000
First Posted:
Apr 21, 2021
Last Update Posted:
Aug 3, 2022
Last Verified:
Aug 1, 2022
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
Yes
Product Manufactured in and Exported from the U.S.:
Yes
Additional relevant MeSH terms:
Macular Degeneration
Wet Macular Degeneration
Ranibizumab

Study Results

No Results Posted as of Aug 3, 2022