A Study of 36-Week Refill Exchanges of Port Delivery System (PDS) With Ranibizumab in nAMD

Official title

A Phase IIIb, Multicenter, Single-arm Study Assessing the Effectiveness, Safety and Patient Reported Outcomes of a 36-week Refill Exchange Regimen for the Port Delivery System With Ranibizumab in Patients With Neovascular Age-related Macular Degeneration

Overview

The purpose of this study is to evaluate the effectiveness, safety, and PROs of the port delivery system with ranibizumab 100 milligrams/milliliters (mg/mL) refilled every 36 weeks (Q36W) in participants with nAMD.

Interventions

• Device Susvimo PDS Implant
  Ranizumab will be administered via a PDS implant per the schedule described in the arm.
• Drug Ranibizumab
  Participants will receive ranibizumab delivered through the PDS implant. Participants will receive ranibizumab, 0.5 mg IVT injections as a supplemental treatment.

Primary outcome measures

• Change From Baseline in Best Corrected Visual Acuity (BCVA) Score Averaged Over Weeks 68 and 72, as Assessed Using the Early Treatment Diabetic Retinopathy Study (ETDRS) Chart at a Starting Distance of 4 Meters [Time frame: Baseline, Week 68, Week 72]

Secondary outcome measures (12)

• Change From Baseline in BCVA Score Over Time [Time frame: From baseline up to Week 72]
• Percentage of Participants Who Lose ≤ 15, ≤ 10, ≤ 5, or Gain ≥ 0 Letters in BCVA Score From Baseline Over Time [Time frame: From baseline up to Week 72]
• Change From Baseline in Center Point Thickness (CPT) [Time frame: From baseline up to Week 72]
• Change From Baseline in Central Subfield Thickness (CST) [Time frame: From baseline up to Week 72]
• Proportion of Participants Who do not Undergo Supplemental Treatment With IVT Ranibizumab Before Each Refill-exchange Procedure [Time frame: Up to Week 72]
• Number of Supplemental Treatments Participants Received in Each Refill Cycle [Time frame: Up to Week 72]
• Frequency of Study Visits in Each Refill Cycle [Time frame: Up to Week 72]
• Proportion of Participants Who Report Preferring PDS Compared With IVT Ranibizumab Treatment as Measured by the PDS Patient Preference Questionnaire (PPPQ) at Weeks 24 and 72 [Time frame: Weeks 24 and 72]
• Proportion of Participants With Bilateral Disease Who Report Preferring PDS Compared With IVT Ranibizumab Treatment Measured by the PPPQ at Weeks 24 and 72 [Time frame: Weeks 24 and 72]
• Number of Participants With Ocular and Systemic (Non-ocular) Adverse Events (AEs) [Time frame: Up to approximately 19 months]
• Number of Participants With Adverse Events of Special Interests (AESIs) and their Severity, Including Ocular AESIs [Time frame: Up to approximately 19 months]
• Number of Participants With Ocular AESIs and Severity of Ocular AESIs During the Post-operative and Follow-up Period [Time frame: Post-operative period: ≤ 37 days of initial implantation surgery Follow-up period: > 37 days after implantation surgery (up to 72 weeks)]

Eligibility criteria

Inclusion criteria

• Initial diagnosis of nAMD within 24 months prior to screening
• Previous treatment with at least 3 anti-vascular endothelial growth factor (VEGF) IVT injections for nAMD per standard of care within 6 months prior to screening
• Demonstrated response to prior anti-VEGF IVT treatment since diagnosis
• Availability of historical VA data obtained at or after nAMD diagnosis and prior to the first anti-VEGF treatment for nAMD
• Availability of historical OCT image data obtained at or after nAMD diagnosis and prior to the first anti-VEGF treatment for nAMD
• BCVA of 34 letters or better using ETDRS chart at a starting distance of 4 meters at screening and enrollment visits

Exclusion criteria

A. Prior Ocular Treatment

Study Eye:

• History of vitrectomy surgery, submacular surgery, or other surgical intervention for age-related macular degeneration (AMD)
• Previous treatment with corticosteroid intravitreal injection
• Previous intraocular device implantation
• History of vitreous hemorrhage
• History of rhegmatogenous retinal detachment
• History of glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery
• History of corneal transplant

Either Eye:

• History of a severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the ranibizumab injections, study-related procedure preparations (including fluorescein), dilating drops, or any of the anesthetic and antimicrobial preparations used by a participant during the study
• Prior participation in a clinical trial involving any experimental therapies for nAMD
• Prior treatment with brolucizumab or gene therapy for nAMD

B. Macular Neovascularization/Choroidal Neovascularization (MNV/CNV) Lesion Characteristics:

Study Eye:

• Subretinal hemorrhage that involves the center of the fovea
• Subfoveal fibrosis or subfoveal atrophy

Either Eye:

• CNV due to other causes, such as ocular histoplasmosis, trauma, central serous chorioretinopathy, or pathologic myopia
• CNV masquerading lesions

C. Concurrent Ocular Conditions:

Study Eye:

• Subfoveal and/or juxtafoveal retinal pigment epithelial tear
• Any concurrent intraocular condition 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
• Retinal tears or peripheral retinal breaks on depressed fundus exam that are untreated or treated within 3 months prior to the enrollment visit
• Aphakia or absence of the posterior capsule
• Uncontrolled ocular hypertension or glaucoma
• History or presence of severe posterior blepharitis, recurrent chalazia or hordeolum, severe dry eye syndrome, or severe allergic conjunctivitis
• Trichiasis
• Corneal neuropathy
• Lagophthalmos or incomplete blink
• Active or history of facial nerve palsy/paresis

Fellow (Non-study) Eye:

\- Non-functioning non-study eye defined as either: BCVA of hand motion or worse OR no physical presence of non-study eye (i.e., monocular)

Either Eye:

• Any active or history of uveitis
• Active or history of keratitis, scleritis, endophthalmitis, or chronic blepharitis
• Suspected or active ocular or periocular infectious conjunctivitis or endophthalmitis
• Active or history of floppy eyelid syndrome
• Active thyroid eye disease

D. Concurrent Systemic Conditions:

• Uncontrolled blood pressure
• Active or history of autoimmune diseases
• History of stroke within the last 3 months prior to informed consent
• Atrial fibrillation diagnosed or worsened within the last 3 months prior to informed consent
• History of myocardial infarction (MI) within the last 3 months prior to informed consent
• Confirmed active systemic infection
• 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
• 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

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

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Poland · 8 centers

• MW-med — Krakow
• Szpital sw. Lukasza — Bielsko-Biala
• Specjalistyczny O?rodek Okulistyczny Oculomedica — Bydgoszcz
• OFTALMIKA Sp. z o.o — Bydgoszcz
• Niepubliczny Zak?ad Opieki Zdrowotnej PRYZMAT-OKULISTYKA — Gliwice
• Klinika Okulistyczna Jasne Błonia Sp. z o. o. — Lódz
• Uniwersytecki Szpital Kliniczny Nr 1 w Lublinie;Klinika Chirurgii Siatkówki i Cia?a Szklis — Lublin
• Centrum Diagnostyki i Mikrochirurgii Oka LENS — Olsztyn

South Korea · 7 centers

• Kyungpook National University Hospital — Daegu
• Ajou University Medical Center — Gyeonggi-do
• Korea University Anam Hospital — Seoul
• Severance Hospital, Yonsei University Health System — Seoul
• Seoul St Mary's Hospital — Seoul
• Boramae Medical Center — Seoul
• Hallym University Kangnam Sacred Heart Hospital — Seoul

France · 6 centers

• Institut Ophtalmologique De l Ouest Jules Verne — Nantes
• Hopital Edouard Herriot - CHU Lyon — Lyon
• Clinique Honore Cave — Montauban
• CHNO des Quinze Vingts — Paris
• CHU Poitiers - CHR La Miletrie — Poitiers
• CHU Strasbourg - Nouvel Hopital Civil — Strasbourg

Germany · 6 centers

• Klinikum Chemnitz gGmbH — Chemnitz
• Universitätkslinikum Düsseldorf, Augenklinik — Düsseldorf
• Universitätsmedizin Göttingen Georg-August-Universität — Göttingen
• Medizinische Hochschule Hannover, Klinik für Augenheilkunde — Hanover
• Universitätsmedizin Rostock — Rostock
• Universitätsklinikum Würzburg, Augenklinik und Poliklinik — Würzburg

Italy · 6 centers

• Ospedale Monaldi - AORN dei Colli — Naples
• Azienda Ospedaliero - Universitaria di Ferrara - Arcispedale Sant'Anna, Sede Ospedale di C — Cona (Ferrara)
• Ospedale Isola Tiberina - Gemelli Isola;UOC Chirurgia Vitreoretinica — Rome
• ASST SANTI PAOLO E CARLO - Presidio San Paolo;SC Oculistica — Milan
• Azienda Ospedaliero-Universitaria Ospedale Maggiore della Carità;S.C.D.U. Oftalmologia — Novara
• A.O.U. Policlinico Paolo Giaccone;Oculistica — Palermo

Thailand · 5 centers

• King Chulalongkorn Memorial Hospital — Bangkok
• Rajavithi Hospital — Bangkok
• Ramathibodi Hospital — Bangkok
• Maharaj Nakorn ChiangMai Hospital — Chiang Mai
• Songklanagarind Hospital — Songkhla

Greece · 4 centers

• "G.Gennimatas" General Hospital of Athens — Athens
• Attikon University General Hospital — Chaïdári
• University General Hospital of Heraklion — Heraklon
• University Hospital of Larissa — Larissa

Austria · 3 centers

• Medizinische Universität Innsbruck — Innsbruck
• Kepler Universitätskliniken GmbH - Med Campus III — Linz
• Landesklinikum Mistelbach — Mistelbach

Czechia · 3 centers

• Klaudianova Nemocnice - Mlada Boleslav;Ophtalmology dpt — Mladá Boleslav
• Faculty Hospital Ostrava — Ostrava
• Ustredni vojenska nemocnice — Prague

Spain · 3 centers

• Hospital Universitario La Paz — Madrid
• Hospital Universitario Virgen del Rocio — Seville
• Hospital Arnau de Vilanova (Valencia) — Valencia

Switzerland · 3 centers

• Berner Augenklinik — Bern
• Pallas Klinik Olten — Olten
• Kantonsspital St. Gallen — Sankt Gallen

United Kingdom · 3 centers

• Leicester Royal Infirmary — Leicester
• Gloucestershire Royal Hospital — Gloucester
• Moorfields Eye Hospital NHS Foundation Trust — London

Denmark · 2 centers

• Aarhus Universitetshospital — Aarhus N
• Rigshospitalet Glostrup — Glostrup Municipality

Identifiers

NCT: NCT06847542 · MR45625 · 2024-516924-32-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗