A Study Of The Efficacy, Safety, And Pharmacokinetics Of The Port Delivery System With Ranibizumab In Chinese Patients With Neovascular Age-Related Macular Degeneration

Neovascular Age Related Macular Degeneration Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05562947
• Other study ID #: YR42983
• Status: Recruiting
• Phase: Phase 3
• Start date: June 28, 2024
• Est. completion date: May 7, 2029

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: YR42983, https://forpatients.roche.co
• Phone: 888-662-6728 (U.S. and Canada)
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the efficacy, safety, and pharmacokinetics of ranibizumab 100 mg/mL delivered Q24W via the PDS implant compared with ranibizumab 0.5 mg delivered as a Q4W intravitreal injection in Chinese patients with nAMD.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 68
• Est. completion date: May 7, 2029
• Est. primary completion date: February 25, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 80 Years

Eligibility

Inclusion Criteria:

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

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

• Demonstrated response to prior anti-VEGF intravitreal 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 FP, FA, ICGA, FAF, and OCT images

Exclusion Criteria:

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 intravitreal injection

• Previous intraocular device implantation (not including intraocular lens implants)

• Previous laser (any type) used for AMD treatment

• Treatment with anti-VEGF agents other than ranibizumab within 1 month prior to the randomization visit

• 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

• 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

• 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 patients 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

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

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

• Choroidal neovascularization due to other causes, such as ocular histoplasmosis, trauma, central serous chorio-retinopathy, or pathologic myopia

• Any history of uveitis

• Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis

Related Conditions & MeSH terms

• Macular Degeneration
• nAMD
• Neovascular Age Related Macular Degeneration
• Wet Macular Degeneration

Intervention

Device:
• PDS with ranibizumab (100 mg/mL)
Patients randomized to the implant arm 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 randomization visit, or at Week 48 visit for patients randomized to the intravitreal arm. After the initial fill of the implant with ranibizumab, patients will receive implant refill-exchanges at fixed 24-week intervals.

Drug:
• Ranibizumab (10 mg/mL)
Patients in the intravitreal arm will receive their first intravitreal injection of 50 uL of the 10 mg/mL ranibizumab (0.5 mg dose) at the Day 1 visit, which will occur at the conclusion of the randomization visit. Afterward, patients will receive intravitreal ranibizumab injections of 50 uL of the 10 mg/mL formulation Q4W at each scheduled study visit until Week 44

Locations

Country	Name	City	State
China	Beijing Hospital	Beijing City
China	The Second Affiliated Hospital of Harbin Medical University; ophthalmology department	Harbin
China	Shanghai First People's Hospital	Shanghai
China	Tianjin Medical University Eye Hospital	Tianjin City
China	Eye Hospital, Wenzhou Medical University	Wenzhou City

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in BCVA score averaged over Weeks 36 and 40, as assessed using the ETDRS visual acuity chart at a starting distance of 4 meters		Baseline up to Week 40
Secondary	Proportion of patients with BCVA score of 38 letters (20/200 approximate Snellen equivalent) or worse averaged over Weeks 36 and 40		Baseline up to Week 40
Secondary	Proportion of patients with BCVA score of 38 letters (20/200 approximate Snellen equivalent) or worse averaged over Weeks 44 and 48		Baseline up to Week 48
Secondary	Proportion of patients with BCVA score of 69 letters (20/40 approximate Snellen equivalent) or better averaged over Weeks 36 and 40		Baseline up to Week 40
Secondary	Proportion of patients with BCVA score of 69 letters (20/40 approximate Snellen equivalent) or better averaged over Weeks 44 and 48		Baseline up to Week 48
Secondary	Proportion of patients who gain =0 letters in BCVA score from baseline averaged over Weeks 36 and 40		Baseline up to Week 40
Secondary	Proportion of patients who gain = 0 letters in BCVA score from baseline averaged over Weeks 44 and 48		Baseline up to Week 48
Secondary	Proportion of patients who lose < 10 or > 5 letters in BCVA score from baseline averaged over Weeks 36 and 40		Baseline up to Week 40
Secondary	Proportion of patients who lose < 10 or > 5 letters in BCVA score from baseline averaged over Weeks 44 and 48		Baseline up to Week 48
Secondary	Change from baseline in CPT at Week 36	CPT = center point thickness	Baseline up to Week 36
Secondary	Change from baseline in CST at Week 36	CST = central subfield thickness	Baseline up to Week 36
Secondary	Change from baseline in CPT at Week 44	CPT = center point thickness	Baseline up to Week 44
Secondary	Change from baseline in CST at Week 44	CST = central subfield thickness	Baseline up to Week 44
Secondary	Proportion of patients in the implant arm who do not undergo supplemental treatment with intravitreal ranibizumab 0.5 mg before the first, second, third, fourth, fifth, and sixth fixed refill exchange intervals		Baseline up to 144 weeks
Secondary	Proportion of patients in the implant arm who do not undergo a supplemental treatment that requires subsequent additional supplemental treatments during the study		Baseline up to 144 weeks
Secondary	Proportion of participants with Adverse Events		Baseline up to 144 weeks
Secondary	Incidence and severity of adverse device effects in the PDS patients		Baseline up to 144 weeks
Secondary	Incidence, causality, severity, and duration of anticipated serious adverse device effects in the PDS patients		Baseline up to 144 weeks
Secondary	Observed serum ranibizumab concentrations at specified timepoints		Baseline, Weeks 4, 12, 24, 28, 36, 48
Secondary	Area under the concentration time curve from 0-24 weeks		Baseline, Weeks 4, 12, 24
Secondary	Maximum serum concentration of ranibizumab		Baseline, Weeks 4, 12, 24, 28, 36, 48
Secondary	Minimum serum concentration of ranibizumab		Baseline, Weeks 4, 12, 24, 28, 36, 48
Secondary	Prevalence of ADAs at baseline and incidence of ADAs during the study		Baseline, Weeks 4, 24, 48
Secondary	Incidence of treatment-emergent ADAs during the study		Baseline, Weeks 4, 24, 48