Clinical trial NCT05562947: A Study of the Efficacy, Safety, and Pharmacokinetics (PK) of the Port Delivery System With Ranibizumab (PDS) in Chinese Participants With Neovascular Age-related Macular Degeneration (nAMD)
Official title: A Phase III, Multicenter, Randomized, Visual Assessor-masked, Active-comparator Study of the Efficacy, Safety, and Pharmacokinetics of the Port Delivery System With Ranibizumab in Chinese Patients With Neovascular Age-related Macular Degeneration
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Neovascular Age-related Macular Degeneration
nAMD
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2022-10-03
Enrollment: 68
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the efficacy, safety, and PK of ranibizumab 100 milligrams per milliliter (mg/mL) delivered every 24 weeks (Q24W) via the PDS implant compared with ranibizumab 0.5 milligrams (mg) delivered every 4 weeks (Q4W) as intravitreal (IVT) injection in chinese participants with nAMD.


Eligibility criteria: Inclusion Criteria:

* Initial diagnosis of nAMD within 9 months prior to the screening visit
* Previous treatment with at least three anti-vascular endothelial growth factor (VEGF) IVT injections for nAMD per standard of care within 6 months prior to the screening visit
* Demonstrated response to prior anti-VEGF IVT treatment since diagnosis
* Availability of historical VA data prior to the first anti-VEGF treatment for nAMD up to the screening visit
* BCVA of 34 letters or better (20/200 or better approximate Snellen equivalent), using Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters
* All subtypes of nAMD lesions are permissible
* Sufficiently clear ocular media and adequate pupillary dilation to allow for analysis and grading by the central reading center of fundus photography (FP), fluorescein angiography (FA), indocyanine green angiography (ICGA), fundus autofluorescence (FAF), and optical coherence tomography (OCT) images

Exclusion Criteria:

A. Prior Ocular Treatment Study Eye

* History of vitrectomy surgery, submacular surgery, or other surgical intervention, all for AMD
* Prior treatment with Visudyne, external-beam radiation therapy, or transpupillary thermotherapy
* Previous treatment with corticosteroid IVT injection
* Previous intraocular device implantation (not including intraocular lens implants)
* Previous laser (any type) used for age-related macular degeneration (AMD) treatment
* Treatment with anti-VEGF agents other than ranibizumab within 1 month prior to the randomization visit
* Prior treatment with intravitreal treatments for geographic atrophy
* Concurrent conjunctival, Tenon's capsule, and/or scleral condition in the supero-temporal quadrant of the eye that may affect the implantation, subsequent tissue coverage, and refill-exchange procedure of the PDS implant

Either Eye

* Prior treatment with brolucizumab
* Prior gene therapy for nAMD or other ocular diseases
* Previous participation in any ocular disease studies of investigational drugs and/or devices, within 3 months or five elimination half-lives of the investigational therapy, whichever is longer, preceding the screening visit

B. Choroidal Neovascularization (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 millimeter square \[mm\^2\]) in size at screening
* Subfoveal fibrosis or subfoveal atrophy

Either Eye • CNV due to other causes, such as ocular histoplasmosis, trauma, central serous chorio-retinopathy, or pathologic myopia

C. Concurrent Ocular Conditions Study Eye

* Retinal pigment epithelial tear
* Any concurrent intraocular condition
* 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 randomization visit
* History of pars plana vitrectomy surgery
* Aphakia or absence of the posterior capsule
* 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
* Intraocular surgery (including cataract surgery) within 3 months preceding the randomization visit
* Uncontrolled ocular hypertension or glaucoma
* History of glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery
* History of corneal transplant

Fellow (Non-Study) Eye

• Non-functioning fellow eye

Either Eye

* Any history of uveitis
* Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis

Primary outcomes:
measure: Change From Baseline in Best-corrected Visual Acuity (BCVA) Score Averaged Over Weeks 36 and 40, as Assessed Using the ETDRS Visual Acuity (VA) Chart at a Starting Distance of 4 Meters
timeFrame: Baseline up to Week 40
Secondary outcomes:
measure: Change From Baseline in BCVA Score Over Time
timeFrame: Baseline up to Week 144
measure: Proportion of Participants With BCVA Score of 38 Letters (20/200 Approximate Snellen Equivalent) or Worse Averaged Over Weeks 36 and 40
timeFrame: Baseline up to Week 40
measure: Proportion of Participants With BCVA Score of 38 Letters (20/200 Approximate Snellen Equivalent) or Worse Averaged Over Weeks 44 and 48
timeFrame: Baseline up to Week 48
measure: Proportion of Participants With BCVA Score of 69 Letters (20/40 Approximate Snellen Equivalent) or Better Averaged over Weeks 36 and 40
timeFrame: Baseline up to Week 40
measure: Proportion of Participants With BCVA Score of 69 Letters (20/40 Approximate Snellen Equivalent) or Better Averaged Over Weeks 44 and 48
timeFrame: Baseline up to Week 48
measure: Proportion of Participants Who Gain ≥0 Letters in BCVA Score From Baseline Averaged Over Weeks 36 and 40
timeFrame: Baseline up to Week 40
measure: Proportion of Participants Who Gain ≥ 0 Letters in BCVA Score From Baseline Averaged Over Weeks 44 and 48
timeFrame: Baseline up to Week 48
measure: Proportion of Participants Who Lose < 10 or < 5 Letters in BCVA Score From Baseline Averaged Over Weeks 36 and 40
timeFrame: Baseline up to Week 40
measure: Proportion of Participants Who Lose < 10 or < 5 Letters in BCVA Score From Baseline Averaged Over Weeks 44 and 48
timeFrame: Baseline up to Week 48
measure: Change From Baseline in Center Point Thickness (CPT) at Week 36
timeFrame: Baseline, Week 36
measure: Change From Baseline in Central Subfield Thickness (CST) at Week 36
timeFrame: Baseline, Week 36
measure: Change From Baseline in CPT at Week 44
timeFrame: Baseline, Week 44
measure: Change From Baseline in CST at Week 44
timeFrame: Baseline, Week 44
measure: Proportion of Participants in the Implant Arm Who do not Undergo Supplemental Treatment With IVT Ranibizumab 0.5 mg Before the First, Second, Third, Fourth, Fifth, and Sixth Fixed Refill-exchange Intervals
timeFrame: Baseline up to 144 weeks
measure: Proportion of Participants in the Implant Arm Who do not Undergo a Supplemental Treatment that Requires Subsequent Additional Supplemental Treatments During the Study
timeFrame: Baseline up to 144 weeks
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: Baseline up to 144 weeks
measure: Percentage of Participants With Adverse Events of Special Interest (AESIs)
timeFrame: Baseline up to 144 weeks
measure: Percentage of Participants With Ocular AESIs During the Post-operative Period and Follow-up Period
timeFrame: Post-operative period: up to 37 days after initial implantation Follow-up period: > 37 days after implantation surgery (up to 144 weeks)
measure: Percentage of Participants Who Received PDS Affected With Adverse Device Effects (ADEs)
timeFrame: Baseline up to 144 weeks
measure: Percentage of Participants Who Received PDS Affected With Anticipated Serious Adverse Device Effects (ASADEs)
timeFrame: Baseline up to 144 weeks
measure: Number of Device Deficiencies
timeFrame: Baseline up to 144 weeks
measure: Observed Serum Ranibizumab Concentrations at Specified Timepoints
timeFrame: Baseline, Weeks 4, 12, 24, 28, 36, 48
measure: Area Under the Concentration Time Curve From 0-24 Weeks
timeFrame: Baseline, Weeks 4, 12, 24
measure: Maximum Serum Concentration of Ranibizumab
timeFrame: Baseline, Weeks 4, 12, 24, 28, 36, 48
measure: Minimum serum concentration of ranibizumab
timeFrame: Baseline, Weeks 4, 12, 24, 28, 36, 48
measure: Number of Participants With Anti-drug Antibodies (ADAs)
timeFrame: Baseline, Weeks 4, 24, 48
measure: Number of Participants With Treatment-emergent ADAs During the Study
timeFrame: Baseline, Weeks 4, 24, 48
Other outcomes:
Locations:
city: Beijing City
country: China
facility: Peking Union Medical College Hospital
city: Beijing
country: China
facility: Beijing Hospital
city: Beijing
country: China
facility: Beijing Tongren Hospital
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospital
city: Guangzhou City
country: China
facility: Zhongshan Ophthalmic Center, Sun Yat-sen University
city: Harbin
country: China
facility: The Second Affiliated Hospital of Harbin Medical University
city: Qingdao City
country: China
facility: Qingdao Eye Hospital of Shandong First Medical University
city: Shanghai
country: China
facility: Shanghai First People's Hospital
city: Shanghai
country: China
facility: Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
city: Taiyuan City
country: China
facility: Shanxi Eye Hospital
city: Tianjin City
country: China
facility: Tianjin Medical University Eye Hospital
city: Wenzhou City
country: China
facility: Eye Hospital, Wenzhou Medical University
city: XI An
country: China
facility: Xi'an People's Hospital (Xi'an Fourth Hospital)
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: