A Study Of The Effectiveness And Safety Of A 36-Week Refill Regimen For The Port Delivery System With Ranibizumab Vs Aflibercept Treat & Extend In Subjects With Neovascular Age-Related Macular Degeneration

NCT ID: NCT05126966

Last Updated: 2024-01-18

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-12-29
• Study Completion Date: 2026-01-30

Brief Summary

This study will evaluate the effectiveness and safety of a 36-week refill regimen for the Port Delivery System with ranibizumab 100 mg/mL (PDS Q36W) compared with intravitreal injections of aflibercept (2 mg) administered per treat-and-extend (aflibercept T&E) in subjects with neovascular (wet) age-related macular degeneration (nAMD).

Conditions

Neovascular Age-Related Macular Degeneration

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Ranibizumab

Subjects will have the implant (filled intra-operatively prior to implantation with approximately 20 µL 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 randomization visit. Subjects will have their implant refilled with ranibizumab at weeks 36 and 72.

Group Type: EXPERIMENTAL

Ranibizumab

Intervention Type: DRUG

Ranibizumab will be administered at a dose of 100 mg/mL delivered via the PDS.

Port Delivery System with ranibizumab (PDS)

Intervention Type: DEVICE

PDS is an investigation intraocular drug delivery device designed to continuously deliver anti-VEGF therapy.

Aflibercept

Subjects will receive intravitreal injections of aflibercept (2mg) administered in the study eye per treat-and-extend. The decision to extend, maintain, or reduce the interval until next treatment will be per investigator judgment.

Group Type: ACTIVE_COMPARATOR

Aflibercept

Intervention Type: DRUG

Aflibercept will be administered at a dose of 2 mg in the study eye per treat-and-extend. The decision to extend, maintain, or reduce the interval until next treatment will be per investigator judgment

Interventions

Ranibizumab

Ranibizumab will be administered at a dose of 100 mg/mL delivered via the PDS.

Intervention Type: DRUG

Aflibercept

Aflibercept will be administered at a dose of 2 mg in the study eye per treat-and-extend. The decision to extend, maintain, or reduce the interval until next treatment will be per investigator judgment

Intervention Type: DRUG

Port Delivery System with ranibizumab (PDS)

PDS is an investigation intraocular drug delivery device designed to continuously deliver anti-VEGF therapy.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. Signed Informed Consent Form

2. Age ≥ 50 years, at time of signing Informed Consent Form

3. Ability and willingness to undertake all scheduled visits and assessments

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

5. Initial diagnosis of nAMD within 9 months prior to the screening visit

6. Previous treatment with at least three anti-VEGF intravitreal injections for nAMD per standard of care within 6 months prior to the screening visit

7. Demonstrated response to prior anti-VEGF intravitreal treatment since diagnosis

8. Availability of historical visual acuity data obtained at or after nAMD diagnosis and prior to the first anti-VEGF treatment for nAMD

9. Availability of historical SD-OCT image data obtained at or after nAMD diagnosis and prior to the first anti-VEGF treatment for nAMD

10. BCVA of 34 letters or better (20/200 or better approximate Snellen equivalent), using ETDRS chart at a starting distance of 4 meters (see the BCVA manual for additional details) at screening and randomization visits

11. With any subtype of nAMD lesions (i.e., type I, type II, type III, or mixed forms per OCT classification, including polypoidal choroidal vasculopathy and retinal angiomatous proliferation)

12. Sufficiently clear ocular media and adequate pupillary dilation to allow for clinical examination and analysis and grading by the central reading center of fundus photography (FP), FA, fundus autofluorescence (FAF) image, and SD-OCT images

Exclusion Criteria

Prior Ocular Treatment - Study Eye

1. History of vitrectomy surgery, submacular surgery, or other surgical intervention for AMD

2. Prior pars plana vitrectomy surgery

3. Prior treatment with Visudyne® (verteporfin for injection), external-beam radiation therapy, or transpupillary thermotherapy

4. Previous treatment with corticosteroid intravitreal injection

5. Previous intraocular device implantation (not including intraocular lens implants)

6. Previous intraocular surgery (including cataract surgery) within 3 months of randomization

7. Previous laser (any type) used for AMD or diabetic retinopathy treatment

8. History of vitreous hemorrhage

9. History of rhegmatogenous retinal detachment

10. 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 implantation, subsequent tissue coverage, and refill-exchange procedure of the PDS implant

11. History of glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery

12. History of corneal transplant

13. History of conjunctival surgery in the superotemporal quadrant (including pterygium surgery)

Prior Ocular Treatment Either Eye:

14. History of a severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the ranibizumab or aflibercept injections, study-related procedure preparations (including fluorescein), dilating drops, or any of the anesthetic and antimicrobial preparations used by a subject during the study

15. Any contraindication to aflibercept as per local label

16. Prior participation in a clinical trial involving any anti-VEGF drugs within 6 months prior to the randomization visit

17. Prior treatment with brolucizumab (at any time prior to the screening visit)

18. Prior treatment with external-beam radiation therapy or brachytherapy

MNV (CNV) Lesion Characteristics Study Eye:

19. Subretinal hemorrhage that involves the center of the fovea, if the hemorrhage is greater than 0.5-disc area (1.27 mm^2) in size at screening

20. Subfoveal fibrosis or subfoveal atrophy

MNV (CNV) Lesion Characteristics Either Eye:

21. CNV due to other causes, such as ocular histoplasmosis, trauma, central serous chorio retinopathy, or pathologic myopia

22. CNV masquerading lesions (e.g., cone dystrophy, adult vitelliform dystrophy, pattern dystrophy)

Concurrent Ocular Conditions Study Eye :

23. Subfoveal and/or juxtafoveal retinal pigment epithelial tear

24. Scleral pathology in the superotemporal quadrant (e.g., scleral thinning or calcification)

25. Conjunctival pathologies (e.g., pterygium, scarring, thinning, fibrosis) in the superotemporal quadrant

26. Any concurrent intraocular condition (e.g., cataract, glaucoma, diabetic retinopathy, epiretinal membrane, amblyopia, or strabismus) 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

27. Active intraocular inflammation (grade trace or above)

28. Rhegmatogenous retinal tears or peripheral retinal breaks on depressed fundus exam that are untreated, or treated within 3 months prior to the randomization visit

29. 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

30. Spherical equivalent of the refractive error demonstrating more than 8 diopters of myopia or evidence of pathologic myopia on depressed fundus exam

31. Preoperative refractive error that exceeds 8 diopters of myopia, for subjects who have undergone prior refractive or cataract surgery in the study eye

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

33. Preoperative refractive error that exceeds 5 diopters of hyperopia, for subjects who have undergone prior refractive or cataract surgery

34. Uncontrolled ocular hypertension or glaucoma (defined as intraocular pressure [IOP] > 25 mmHg or a cup to disc ratio > 0.8, despite treatment with anti-glaucoma medication) and any such condition the investigator determines may require a glaucoma-filtering surgery during a subject's participation in the study

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

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

37. Trichiasis

38. Corneal neuropathy

39. Lagophthalmos or incomplete blink

40. Active or history of facial nerve palsy/paresis

Concurrent Ocular Conditions Non-Study (Fellow) Eye

41. Non-functioning non-study eye, defined as either:

1. BCVA of hand motion or worse

2. No physical presence of non-study eye (i.e., monocular)

3. Legally blind in the subject's relevant jurisdiction

Concurrent Ocular Conditions Either Eye

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

43. Active or history of keratitis, scleritis, endophthalmitis, or chronic blepharitis

44. Suspected or active ocular or periocular infectious conjunctivitis or endophthalmitis

45. Active or history of Sjogrens syndrome or keratoconjunctivitis sicca

46. Active or history of floppy eyelid syndrome

47. Active or history of chronic eye rubbing

48. Active thyroid eye disease

Concurrent Systemic Conditions:

49. Inability to comply with study schedule or procedures as described in the study protocol

50. Uncontrolled blood pressure (defined as systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 110 mmHg, while a subject is at rest) If a subject's initial measurement exceeds these values, a second reading should be taken ≥ 30 minutes after the first reading If the subject's blood pressure must be controlled by antihypertensive medication, the subject may become eligible if medication is taken continuously for at least 30 days prior to Day 1

51. Active or history of autoimmune diseases, for example, rheumatoid arthritis, lupus, granulomatosis with polyangiitis (Wegner's)

52. History of stroke within the last 3 months prior to informed consent

53. Atrial fibrillation diagnosed or worsened within the last 3 months prior to informed consent

54. History of myocardial infarction within the last 3 months prior to informed consent

55. History of other disease, metabolic dysfunction (including uncontrolled diabetes), or clinical laboratory finding (after reviewing the results of the screening laboratory results) giving reasonable suspicion of a disease or condition that contraindicates the use of ranibizumab, aflibercept, or placement of the implant and that might affect interpretation of the results of the study or renders the subject at high risk of treatment complications in the opinion of the investigator

56. Confirmed active systemic infection

57. Use of any systemic anti-VEGF agents

58. Chronic use of oral corticosteroids (> 10 mg/day of prednisone or equivalent)

59. Active cancer within 12 months of randomization 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

60. Previous participation in any non-ocular (systemic) disease studies of investigational drugs within 1 month preceding the informed consent (excluding vitamins and minerals)

61. Use of antimitotic or antimetabolite therapy within 30 days or 5 elimination half-lives of the randomization visit

62. Requirement for continuous use of any medications or treatments prohibited in the study

63. Pregnant or breastfeeding, or intending to become pregnant during the treatment period and for at least 3 months after the final intravitreal injection of ranibizumab or aflibercept, or 1 year after the last implant refill-exchange procedure

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Oftalmos

Capital Federal, , Argentina

Rigshospitalet Glostrup; Afdeling for Øjensygdomme

Glostrup Municipality, , Denmark

Sjællands Universitetshospital, Roskilde; Øjenafdelingen

Roskilde, , Denmark

University Hospital of Larissa; Department of Ophthalmology

Larissa, , Greece

Queen Mary Hospital; Department of Ophthalmology

Hong Kong, , Hong Kong

Hong Kong Eye Hospital; CUHK Eye Centre

Mong Kok, , Hong Kong

Hospital de Sao Joao; Servico de Oftalmologia

Porto, , Portugal

Hospital de la Arruzafa. Servicio de Oftalmologia

Córdoba, , Spain

King Chulalongkorn Memorial Hospital; Ophthalmology Department

Bangkok, , Thailand

Maharaj Nakorn ChiangMai Hospital; Ophthalmology Department

Chiang Mai, , Thailand

Countries

Argentina; Denmark; Greece; Hong Kong; Portugal; Spain; Thailand

Other Identifiers

2021-003226-71

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MR42410

Identifier Type: -

Identifier Source: org_study_id