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Trial record 1 of 2 for:    GR40548
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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03677934
Recruitment Status : Completed
First Posted : September 19, 2018
Results First Posted : March 25, 2022
Last Update Posted : March 25, 2022
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Description
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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).

Condition or disease Intervention/treatment Phase
Neovascular Age-Related Macular Degeneration Drug: PDS Implant filled with 100 mg/mL Ranibizumab Drug: Intravitreal Injections of 10 mg/mL Ranibizumab Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 415 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : September 12, 2018
Actual Primary Completion Date : May 22, 2020
Actual Study Completion Date : June 9, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Ranibizumab

Arms and Interventions
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Arm Intervention/treatment
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
 Drug: PDS Implant filled with 100 mg/mL Ranibizumab
Will be administered as per the schedule described in individual arm.
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.
 Drug: Intravitreal Injections of 10 mg/mL Ranibizumab
Will be administered as per the schedule described in individual arm.


Outcome Measures
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Primary Outcome Measures :
  1. 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.



Secondary Outcome Measures :
  1. Change From Baseline in BCVA Score Averaged Over Week 60 and Week 64 [ Time Frame: Baseline to Week 64 ]
  2. Change From Baseline in BCVA Score Over Time [ Time Frame: Baseline up to Week 96 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. Percentage of Participants Who Lose <10 or <5 Letters in BCVA Score From Baseline Over Time [ Time Frame: Baseline up to Week 96 ]
  9. 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 ]
  10. Percentage of Participants Who Gain ≥0 Letters in BCVA Score From Baseline Over Time [ Time Frame: Baseline up to Week 96 ]
  11. Change From Baseline in Center Point Thickness (CPT) at Week 36 [ Time Frame: Baseline to Week 36 ]
  12. Change From Baseline in CPT Over Time [ Time Frame: Baseline up to Week 96 ]
  13. 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: Week 16 to Week 92 ]
  14. 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 ]
  15. Incidence and Severity of Ocular and Systemic (Non-Ocular) AEs [ Time Frame: Randomization to Week 96 ]
    AEs = Adverse Events

  16. Incidence, Severity, and Duration of AESIs [ Time Frame: Randomization to Week 96 ]
    AESIs = Adverse Events of Special Interest

  17. Incidence, Severity, and Duration of PDS-Associated AESIs During the Postoperative Period (up to 37 Days of Initial Implantation) and Follow-Up Period (>37 Days After Implantation Surgery) [ Time Frame: Randomization to Week 96 ]
  18. Observed Serum Ranibizumab Concentrations at Specified Timepoints [ Time Frame: Randomization to Week 96 ]
  19. 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

  20. Estimated PK Parameter Value t1/2 After PDS Implant Insertion [ Time Frame: Randomization to Week 96 ]
    t1/2 = Half-Life

  21. Estimated PK Parameter Value Cmin [ Time Frame: Randomization to Week 96 ]
    Cmin = Minimum Serum Concentration

  22. Estimated PK Parameter Value Cmax [ Time Frame: Randomization to Week 96 ]
    Cmax = Maximum Serum Concentration

  23. Participants Who Were ADA Negative at Baseline and Became Positive Only After Dosing [ Time Frame: Randomization to Week 96 ]
    ADA = Anti-Drug Antibody

  24. Participants Who Were ADA Positive at Randomization and ADA Titer Increased After Dosing [ Time Frame: Randomization to Week 96 ]
  25. Participants Who Were ADA Positive at Randomization and ADA Titer Did Not Increase After Dosing [ Time Frame: Randomization to Week 96 ]

Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03677934


Locations
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Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
  Study Documents (Full-Text)

Documents provided by Hoffmann-La Roche:
Study Protocol  [PDF] February 2, 2021
Statistical Analysis Plan  [PDF] April 9, 2021

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03677934    
Other Study ID Numbers: GR40548
First Posted: September 19, 2018    Key Record Dates
Results First Posted: March 25, 2022
Last Update Posted: March 25, 2022
Last Verified: February 2022
Individual Participant Data (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).

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Macular Degeneration
Wet Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases
Ranibizumab
 Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents