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

Primary Purpose

Neovascular Age Related Macular Degeneration, nAMD

Status

Not yet recruiting

Phase

Phase 3

Locations

China

Study Type

Interventional

Intervention

PDS with ranibizumab (100 mg/mL)

Ranibizumab (10 mg/mL)

About this trial

This is an interventional treatment trial for Neovascular Age Related Macular Degeneration

Eligibility Criteria

50 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Eye Hospital, Wenzhou Medical University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Implant arm

Intravitreal arm

Arm Description

Participants will have the implant (pre-filled intraoperatively with ranibizumab 100 mg/mL) surgically inserted on Day 1. After Day 1, patients in the implant arm will attend monthly study visits, and receive implant refill-exchanges with ranibizumab 100 mg/mL at Week 24 and Week 48. At the Week 48 study visit, patients will move to the long term extension phase of the study and continue receiving refill-exchanges Q24W until the end of study. Patients will attend monthly visits up to Week 96 and bi-monthly visits, thereafter

Participants will receive intravitreal ranibizumab 0.5 mg injections starting on Day 1. Patients will receive intravitreal ranibizumab 0.5 mg Q4W until Week 44. At the Week 48 study visit, patients will receive the PDS implant (pre-filled intraoperatively with ranibizumab 100 mg/mL), move to the long-term extension phase of the study and receive Q24W refill exchanges until the end of study. If patients are unable to attend the Week 48 visit due to extenuating circumstances, they should return no later than the next scheduled visit (Week 52), when they will receive the PDS implant. Patients will attend monthly visits up to Week 96 and bi-monthly visits, thereafter.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Proportion of patients with BCVA score of 38 letters (20/200 approximate Snellen equivalent) or worse averaged over Weeks 36 and 40

Proportion of patients with BCVA score of 38 letters (20/200 approximate Snellen equivalent) or worse averaged over Weeks 44 and 48

Proportion of patients with BCVA score of 69 letters (20/40 approximate Snellen equivalent) or better averaged over Weeks 36 and 40

Proportion of patients with BCVA score of 69 letters (20/40 approximate Snellen equivalent) or better averaged over Weeks 44 and 48

Proportion of patients who gain ≥0 letters in BCVA score from baseline averaged over Weeks 36 and 40

Proportion of patients who gain ≥ 0 letters in BCVA score from baseline averaged over Weeks 44 and 48

Proportion of patients who lose < 10 or > 5 letters in BCVA score from baseline averaged over Weeks 36 and 40

Proportion of patients who lose < 10 or > 5 letters in BCVA score from baseline averaged over Weeks 44 and 48

Change from baseline in CPT at Week 36

CPT = center point thickness

Change from baseline in CST at Week 36

CST = central subfield thickness

Change from baseline in CPT at Week 44

CPT = center point thickness

Change from baseline in CST at Week 44

CST = central subfield thickness

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

Proportion of patients in the implant arm who do not undergo a supplemental treatment that requires subsequent additional supplemental treatments during the study

Proportion of participants with Adverse Events

Incidence and severity of adverse device effects in the PDS patients

Incidence, causality, severity, and duration of anticipated serious adverse device effects in the PDS patients

Observed serum ranibizumab concentrations at specified timepoints

Area under the concentration time curve from 0-24 weeks

Maximum serum concentration of ranibizumab

Minimum serum concentration of ranibizumab

Prevalence of ADAs at baseline and incidence of ADAs during the study

Incidence of treatment-emergent ADAs during the study

Full Information

NCT ID

NCT05562947

First Posted

September 15, 2022

Last Updated

September 28, 2023

Sponsor

Hoffmann-La Roche

1. Study Identification

Unique Protocol Identification Number

NCT05562947

Brief Title

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

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

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

May 10, 2024 (Anticipated)

Primary Completion Date

February 25, 2027 (Anticipated)

Study Completion Date

May 7, 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hoffmann-La Roche

4. Oversight

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

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Neovascular Age Related Macular Degeneration, nAMD

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

Outcomes Assessor

Allocation

Randomized

Enrollment

68 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Implant arm

Arm Type

Experimental

Arm Description

Arm Title

Intravitreal arm

Arm Type

Experimental

Arm Description

Intervention Type

Device

Intervention Name(s)

PDS with ranibizumab (100 mg/mL)

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Ranibizumab (10 mg/mL)

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Time Frame

Baseline up to Week 40

Secondary Outcome Measure Information:

Title

Proportion of patients with BCVA score of 38 letters (20/200 approximate Snellen equivalent) or worse averaged over Weeks 36 and 40

Time Frame

Baseline up to Week 40

Title

Proportion of patients with BCVA score of 38 letters (20/200 approximate Snellen equivalent) or worse averaged over Weeks 44 and 48

Time Frame

Baseline up to Week 48

Title

Proportion of patients with BCVA score of 69 letters (20/40 approximate Snellen equivalent) or better averaged over Weeks 36 and 40

Time Frame

Baseline up to Week 40

Title

Proportion of patients with BCVA score of 69 letters (20/40 approximate Snellen equivalent) or better averaged over Weeks 44 and 48

Time Frame

Baseline up to Week 48

Title

Proportion of patients who gain ≥0 letters in BCVA score from baseline averaged over Weeks 36 and 40

Time Frame

Baseline up to Week 40

Title

Proportion of patients who gain ≥ 0 letters in BCVA score from baseline averaged over Weeks 44 and 48

Time Frame

Baseline up to Week 48

Title

Proportion of patients who lose < 10 or > 5 letters in BCVA score from baseline averaged over Weeks 36 and 40

Time Frame

Baseline up to Week 40

Title

Proportion of patients who lose < 10 or > 5 letters in BCVA score from baseline averaged over Weeks 44 and 48

Time Frame

Baseline up to Week 48

Title

Change from baseline in CPT at Week 36

Description

CPT = center point thickness

Time Frame

Baseline up to Week 36

Title

Change from baseline in CST at Week 36

Description

CST = central subfield thickness

Time Frame

Baseline up to Week 36

Title

Change from baseline in CPT at Week 44

Description

CPT = center point thickness

Time Frame

Baseline up to Week 44

Title

Change from baseline in CST at Week 44

Description

CST = central subfield thickness

Time Frame

Baseline up to Week 44

Title

Time Frame

Baseline up to 144 weeks

Title

Proportion of patients in the implant arm who do not undergo a supplemental treatment that requires subsequent additional supplemental treatments during the study

Time Frame

Baseline up to 144 weeks

Title

Proportion of participants with Adverse Events

Time Frame

Baseline up to 144 weeks

Title

Incidence and severity of adverse device effects in the PDS patients

Time Frame

Baseline up to 144 weeks

Title

Incidence, causality, severity, and duration of anticipated serious adverse device effects in the PDS patients

Time Frame

Baseline up to 144 weeks

Title

Observed serum ranibizumab concentrations at specified timepoints

Time Frame

Baseline, Weeks 4, 12, 24, 28, 36, 48

Title

Area under the concentration time curve from 0-24 weeks

Time Frame

Baseline, Weeks 4, 12, 24

Title

Maximum serum concentration of ranibizumab

Time Frame

Baseline, Weeks 4, 12, 24, 28, 36, 48

Title

Minimum serum concentration of ranibizumab

Time Frame

Baseline, Weeks 4, 12, 24, 28, 36, 48

Title

Prevalence of ADAs at baseline and incidence of ADAs during the study

Time Frame

Baseline, Weeks 4, 24, 48

Title

Incidence of treatment-emergent ADAs during the study

Time Frame

Baseline, Weeks 4, 24, 48

10. Eligibility

Sex

All

Minimum Age & Unit of Time

50 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Reference Study ID Number: YR42983, https://forpatients.roche.com/

Phone

888-662-6728 (U.S. and Canada)

global-roche-genentech-trials@gene.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Trials

Organizational Affiliation

Hoffmann-La Roche

Official's Role

Study Director

Facility Information:

Facility Name

Eye Hospital, Wenzhou Medical University

City

Wenzhou City

ZIP/Postal Code

325027

Country

China

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

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

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