A Phase III Study to Evaluate the Port Delivery System With Ranibizumab Compared With Monthly Ranibizumab Injections in Participants With Wet Age-Related Macular Degeneration (Archway)

• ClinicalTrials.gov Identifier: NCT03677934
• Recruitment Status: Completed
• First Posted: September 19, 2018
• Results First Posted: March 25, 2022
• Last Update Posted: October 4, 2022
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: September 11, 2018
• First Posted Date: September 19, 2018
• Results First Submitted Date: November 18, 2021
• Results First Posted Date: March 25, 2022
• Last Update Posted Date: October 4, 2022
• Actual Study Start Date: September 12, 2018
• Actual Primary Completion Date: May 22, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 28, 2022)

Change From Baseline in Best-Corrected Visual Acuity (BCVA) Score at the Average of Week 36 and Week 40, as Assessed Using the ETDRS Visual Acuity Chart at a Starting Distance of 4 Meters [ Time Frame: Baseline, and the average of Week 36 and Week 40 ]

The primary efficacy endpoint is the change in BCVA score from baseline averaged over Weeks 36 and 40 with BCVA assessed using the ETDRS chart at a starting distance of 4 meters. ETDRS = Early Treatment Diabetic Retinopathy Study. The primary objective is to determine the NI and equivalence between the two treatment groups, as measured by the primary efficacy endpoint with a NI margin of 4.5 letters and equivalence margins of ± 4.5 letters. A vision score of 20/20 vision is considered normal. A score of 20/200 is considered being legally blind.

Original Primary Outcome Measures (submitted: September 18, 2018)

Change from Baseline in Best-Corrected Visual Acuity (BCVA) Score at the Average of Week 36 and Week 40, as Assessed Using the EDTRS Visual Acuity Chart at a Starting Distance of 4 Meters [ Time Frame: Baseline to Week 40 ]

EDTRS = Early Treatment Diabetic Retinopathy Study A vision score of 20/20 vision is considered normal. A score of 20/200 is considered being legally blind.

Current Secondary Outcome Measures (submitted: September 6, 2022)

• Change From Baseline in BCVA Score Averaged Over Week 60 and Week 64 [ Time Frame: Baseline, Week60, Week 64 ]
• Change From Baseline in BCVA Score Over Time [ Time Frame: Baseline up to Week 96 ]
• Percentage of Participants With BCVA Score of 38 Letters (20/200 Approximate Snellen Equivalent) or Worse at the Average Over Week 36 and Week 40 [ Time Frame: Baseline, and the average of Week 36 and Week 40 ]
• Percentage of Participants With BCVA Score of 38 Letters (20/200 Approximate Snellen Equivalent) or Worse Over Time [ Time Frame: Baseline up to Week 96 ]
• Percentage of Participants With BCVA Score of 69 Letters (20/40 Approximate Snellen Equivalent) or Better at the Average Over Week 36 and Week 40 [ Time Frame: Baseline, and the average of Week 36 and Week 40 ]
• Percentage of Participants With BCVA Score of 69 Letters (20/40 Approximate Snellen Equivalent) or Better Over Time [ Time Frame: Baseline up to Week 96 ]
• Percentage of Participants Who Lose <10 or <5 Letters in BCVA Score From Baseline to the Average Over Week 36 and Week 40 [ Time Frame: Baseline, and the average of Week 36 and Week 40 ]
• Percentage of Participants Who Lose <10 or <5 Letters in BCVA Score From Baseline Over Time [ Time Frame: Baseline up to Week 96 ]
• Percentage of Participants Who Gain ≥0 Letters in BCVA Score From Baseline to the Average Over Week 36 and Week 40 [ Time Frame: Baseline up to Week 40 ]
• Percentage of Participants Who Gain ≥0 Letters in BCVA Score From Baseline Over Time [ Time Frame: Baseline up to Week 96 ]
• Change From Baseline in Center Point Thickness (CPT) at Week 36 [ Time Frame: Baseline to Week 36 ]
• Change From Baseline in CPT Over Time [ Time Frame: Baseline up to Week 96 ]
• Percentage of Participants in the PDS Implant Arm Who Undergo Supplemental Treatment With Intravitreal Ranibizumab 0.5 mg Before the First, Second, Third, and Fourth Fixed Refill-Exchange Intervals [ Time Frame: Day 1 to Week 24, Week 25 to Week 48, Week 49 to Week 72, Week73 to Week 96 ]
• Percentage of Participants in the PDS Implant Arm Who Undergo a Supplemental Treatment That Requires Subsequent Additional Supplemental Treatments During the Study [ Time Frame: Week 16 to Week 92 ]
• Percentage of Participants With Ocular and Systemic (Non-Ocular) AEs [ Time Frame: Randomization to Week 96 ]
• Percentage of Participants With Adverse Events of Special Interest [ Time Frame: Randomization to Week 96 ]
  Percentage of Participants with Adverse Events of Special Interest
• Observed Serum Ranibizumab Concentrations at Specified Timepoints [ Time Frame: Randomization to Week 96 ]
• Estimated PK Parameter Values AUC0-6M [ Time Frame: Randomization to Week 96 ]
  AUC0-6M = Area Under the Concentration-Time Curve From 0 to 6 Months
• Estimated PK Parameter Value t1/2 After PDS Implant Insertion [ Time Frame: Randomization to Week 96 ]
  Apparent terminal half-life
• Estimated PK Parameter Value Cmin [ Time Frame: Randomization to Week 96 ]
  Cmin = Minimum Serum Concentration
• Estimated PK Parameter Value Cmax [ Time Frame: Randomization to Week 96 ]
  Cmax = Maximum Serum Concentration
• Baseline Prevalence and Incidence of Treatment-Emergent ADA [ Time Frame: Randomization to Week 96 ]

Original Secondary Outcome Measures (submitted: September 18, 2018)

• Percentage of Participants Who Lose <15 Letters in BCVA Score From Baseline to the Average Over Week 36 and Week 40 [ Time Frame: Baseline to Week 40 ]
• Percentage of Participants Who Lose <15 Letters in BCVA From Baseline Over Time [ Time Frame: Baseline up to Week 96 ]
• Change from Baseline in BCVA Score Averaged Over Week 60 and Week 64 [ Time Frame: Baseline to Week 64 ]
• Change From Baseline in BCVA Score Over Time [ Time Frame: Baseline up to Week 96 ]
• Percentage of Participants With BCVA Score of 34 Letters (20/200 Approximate Snellen Equivalent) or Worse at the Average Over Week 36 and Week 40 [ Time Frame: Baseline to Week 40 ]
• Percentage of participants With BCVA Score of 34 Letters (20/200 Approximate Snellen Equivalent) or Worse Over Time [ Time Frame: Baseline up to Week 96 ]
• Percentage of participants With BCVA Score of 69 Letters (20/40 Approximate Snellen Equivalent) or Better at the Average Over Week 36 and Week 40 [ Time Frame: Baseline to Week 40 ]
• Percentage of Participants With BCVA Score of 69 Letters (20/40 Approximate Snellen Equivalent) or Better Over Time [ Time Frame: Baseline up to Week 96 ]
• Percentage of Participants who Lose <10, <5, or <0 Letters in BCVA score from Baseline to the Average Over Week 36 and Week 40 [ Time Frame: Baseline to Week 40 ]
• Percentage of Participants who Lose <10, <5, or <0 Letters in BCVA Score From Baseline Over Time [ Time Frame: Baseline up to Week 96 ]
• Change From Baseline in Center Point Thickness (CPT) at Week 36 [ Time Frame: Baseline to Week 36 ]
• Change From Baseline in CPT Over Time [ Time Frame: Baseline up to Week 96 ]
• Percentage of Participants in the Implant Arm Who Undergo Rescue Treatment of Intravitreal Ranibizumab Before the First, Second, Third, and Fourth Fixed Refill Intervals [ Time Frame: Week 16 to Week 92 ]
• Percentage of Participants in the Implant Arm That Undergo a Rescue Treatment That Requires Subsequent Additional Rescue Treatments During the Study [ Time Frame: Week 16 to Week 92 ]
• Incidence and Severity of Ocular and Systemic (Non-Ocular) AEs [ Time Frame: Randomization to Week 96 ]
  AEs = Adverse Events
• Incidence, Severity, and Duration of AESIs, Including PDS-Associated AEs [ Time Frame: Randomization to Week 96 ]
  AESIs = Adverse Events of Special Interest
• Incidence, Severity, and Duration of PDS-Associated Ocular AEs During the Postoperative Period (up to 4 Weeks of Initial Implantation) and Follow-Up Period (>4 Weeks After Implantation Surgery) [ Time Frame: Randomization to Week 96 ]
• Observed Serum Ranibizumab Concentrations at Specified Timepoints [ Time Frame: Randomization to Week 96 ]
• Estimated PK Parameter Values AUC0-6M [ Time Frame: Randomization to Week 96 ]
  AUC0-6M = Area Under the Concentration-Time Curve From 0 to 6 Months
• Estimated PK Parameter Value t1/2 After PDS Implant Insertion [ Time Frame: Randomization to Week 96 ]
  t1/2 = Half-Life
• Estimated PK Parameter Value Cmin [ Time Frame: Randomization to Week 96 ]
  Cmin = Minimum Serum Concentration
• Estimated PK Parameter Value Cmax [ Time Frame: Randomization to Week 96 ]
  Cmax = Maximum Serum Concentration
• Participants who Were ADA Negative at Baseline and Became Positive Only After Dosing [ Time Frame: Randomization to Week 96 ]
  ADA = Anti-Drug Antibody
• Participants who Were ADA Positive at Randomization and ADA Titer Increased After Dosing [ Time Frame: Randomization to Week 96 ]
• Participants who Were ADA Positive at Randomization and ADA Titer did not Increase After Dosing [ Time Frame: Randomization to Week 96 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase III Study to Evaluate the Port Delivery System With Ranibizumab Compared With Monthly Ranibizumab Injections in Participants With Wet Age-Related Macular Degeneration
• Official Title: Phase III, Multicenter, Randomized, Visual Assessor-Masked, Active-Comparator Study of the Efficacy, Safety, and Pharmacokinetics of the Port Delivery System With Ranibizumab in Patients With Neovascular Age-Related Macular Degeneration
• Brief Summary: Study GR40548 is a Phase III, randomized, multicenter, open-label (visual assessor [VA]-masked), active-comparator study designed to assess the efficacy, safety, and pharmacokinetics (PK) of 100mg/ml delivered via the Port Delivery System with ranibizumab (PDS) compared with ranibizumab intravitreal injections at 0.5 mg (10 mg/mL) in participants with neovascular age-related macular degeneration (nAMD).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment
• Condition: Neovascular Age-Related Macular Degeneration

Intervention

• Drug: PDS Implant filled with 100 mg/mL Ranibizumab
  Will be administered as per the schedule described in individual arm.
• Drug: Intravitreal Injections of 10 mg/mL Ranibizumab
  Will be administered as per the schedule described in individual arm.

Study Arms

• Experimental: PDS Implant Arm
  Participants will receive ranibizumab delivered through the PDS implant with 100 mg/mL in the study eye on Day 1 and receive refill-exchanges at fixed 24-week intervals
  Intervention: Drug: PDS Implant filled with 100 mg/mL Ranibizumab
• Active Comparator: Intravitreal Arm
  Participants will receive ranibizumab 0.5 mg monthly intravitreal injections of 10 mg/mL formulation at Day 1 and every month thereafter.
  Intervention: Drug: Intravitreal Injections of 10 mg/mL Ranibizumab

Publications *

• Chang MA, Kapre A, Kaufman D, Kardatzke DR, Rabena M, Patel S, Bobbala A, Gune S, Fung A, Wallenstein G. Patient Preference and Treatment Satisfaction With a Port Delivery System for Ranibizumab vs Intravitreal Injections in Patients With Neovascular Age-Related Macular Degeneration: A Randomized Clinical Trial. JAMA Ophthalmol. 2022 Aug 1;140(8):771-778. doi: 10.1001/jamaophthalmol.2022.1091.
• Awh CC, Barteselli G, Makadia S, Chang RT, Stewart JM, Wieland MR, Brassard R, Callaway NF, Gune S, Heatherton P, Malhotra V, Willis JR, Pieramici DJ. Management of Key Ocular Adverse Events in Patients Implanted with the Port Delivery System with Ranibizumab. Ophthalmol Retina. 2022 Nov;6(11):1028-1043. doi: 10.1016/j.oret.2022.05.011. Epub 2022 May 16.
• Heimann F, Barteselli G, Brand A, Dingeldey A, Godard L, Hochstetter H, Schneider M, Rothkegel A, Wagner C, Horvath J, Ranade S. A custom virtual reality training solution for ophthalmologic surgical clinical trials. Adv Simul (Lond). 2021 Apr 16;6(1):12. doi: 10.1186/s41077-021-00167-z.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 28, 2022): 415
• Original Estimated Enrollment (submitted: September 18, 2018): 360
• Actual Study Completion Date: June 9, 2021
• Actual Primary Completion Date: May 22, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Age ≥50 years, at time of signing Informed Consent Form
• Initial diagnosis of exudative neovascular age-related macular degeneration (nAMD) within 9 months prior to the screening visit
• Previous treatment with at least three anti-vascular endothelial growth factor (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
• Best-corrected visual acuity (BCVA) of 34 letters or better

Exclusion Criteria:

• Subfoveal fibrosis or subfoveal atrophy in study eye
• Subretinal hemorrhage that involves the center of the fovea in study eye
• History of vitrectomy surgery, submacular surgery, or other surgical intervention for AMD in study eye
• Prior treatment with Visudyne®, external-beam radiation therapy, or transpupillary thermotherapy in study eye
• Previous intraocular device implantation in study eye
• Previous laser (any type) used for AMD treatment in study eye
• Treatment with anti-VEGF agents other than ranibizumab within 1 month prior to the randomization visit in either eye
• Prior participation in a clinical trial involving anti-VEGF drugs within 6 months prior to the randomization visit, other than ranibizumab in either eye
• CNV due to other causes, such as ocular histoplasmosis, trauma, or pathologic myopia in either eye
• Uncontrolled blood pressure
• History of stroke within the last 3 months prior to informed consent
• Uncontrolled atrial fibrillation within 3 months of informed consent
• History of myocardial infarction within the last 3 months prior to informed consent
• 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 or renders the participant at high risk of treatment complications in the opinion of the investigator
• Current systemic treatment for a confirmed active systemic infection
• Chronic use of oral corticosteroids
• Active cancer within 12 months of randomization
• Previous participation in any non-ocular (systemic) disease studies of investigational drugs within 1 month preceding the informed consent (excluding vitamins and minerals)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03677934
• Other Study ID Numbers: GR40548
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on Sharing of Clinical Study 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).

• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: September 2022