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Trial record 1 of 1 for:    NCT04503551
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A Multicenter, Randomized Study in Participants With Diabetic Retinopathy Without Center-involved Diabetic Macular Edema To Evaluate the Efficacy, Safety, and Pharmacokinetics of Ranibizumab Delivered Via the Port Delivery System Relative to the Comparator Arm (PAVILION)

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ClinicalTrials.gov Identifier: NCT04503551
Recruitment Status : Active, not recruiting
First Posted : August 7, 2020
Last Update Posted : September 13, 2023
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Description
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Brief Summary:
Study GR41675 is a Multicenter, Randomized Study in Participants with Diabetic Retinopathy (DR) Without Center-Involved Diabetic Macular Edema (CI-DME) to Evaluate the Efficacy, Safety of the Port Delivery System with Ranibizumab (PDS) Relative to the Comparator Arm

Condition or disease Intervention/treatment Phase
Diabetic Retinopathy Drug: PDS Implant Pre-Filled with 100 mg/mL Ranibizumab Drug: Intravitreal Ranibizumab 0.5 mg Injection Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 174 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Masking Description: The visual acuity examiner will only conduct refraction and visual acuity assessments and will be masked, as best as possible, to the following items: study eye assignment; study visit type; and treatment assignment.
Primary Purpose: Treatment
Official Title: A Phase III, Multicenter, Randomized Study of the Efficacy, Safety, and Pharmacokinetics of the Port Delivery System With Ranibizumab in Patients With Diabetic Retinopathy
Actual Study Start Date : August 10, 2020
Actual Primary Completion Date : October 3, 2022
Estimated Study Completion Date : May 7, 2024

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 Arm
Participants randomized to the PDS arm will receive two intravitreal ranibizumab injections and will then have the PDS implant (pre-filled with ranibizumab) surgically inserted. PDS implant refill-exchange procedures will be performed on a fixed interval every 36-weeks (Q36W) thereafter
 Drug: PDS Implant Pre-Filled with 100 mg/mL Ranibizumab
Will be administered as per the schedule described in individual arm.

Drug: Intravitreal Ranibizumab 0.5 mg Injection
Will be administered as per the schedule described in individual arm.
Comparator Arm
Participants randomized to the comparator arm will undergo study visits every 4 weeks (Q4W) for comprehensive clinical monitoring until they receive the PDS implant (pre-filled with ranibizumab). PDS implant refill-exchange procedures will be performed on a fixed interval Q36W thereafter. Participants will be eligible to receive intravitreal ranibizumab 0.5 mg injections if treatment eligibility criteria are met.
 Drug: PDS Implant Pre-Filled with 100 mg/mL Ranibizumab
Will be administered as per the schedule described in individual arm.

Drug: Intravitreal Ranibizumab 0.5 mg Injection
Will be administered as per the schedule described in individual arm.


Outcome Measures
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Primary Outcome Measures :
  1. Percentage of participants with a ≥2-step improvement from baseline on the ETDRS-DRSS at Week 52 [ Time Frame: Week 52 ]

    ETDRS = Early Treatment Diabetic Retinopathy Study

    DRSS = Diabetic Retinopathy Severity Scale

    The ETDRS-DRSS includes 13 score levels, ranging from the absence of retinopathy to PDR, including neovascularization and/or vitreous/preretinal hemorrhage.



Secondary Outcome Measures :
  1. Rate of participants developing a vision-threatening complication (defined as PDR, ASNV, or CI-DME [defined as central foveal thickness [CST] ≥325 μm on spectral-domain optical coherence tomography [SD-OCT]) through Week 52 [ Time Frame: From baseline through 52 weeks ]
    PDR = proliferative diabetic retinopathy ASNV = Anterior segment neovascularization

  2. Rate of participants developing PDR or ASNV through Week 52 [ Time Frame: From baseline through 52 weeks ]
  3. Rate of participants developing CI-DME through Week 52 [ Time Frame: From baseline through 52 weeks ]
  4. Rate of participants developing a ≥ 2-step worsening from baseline on the ETDRS-DRSS through Week 52 [ Time Frame: From baseline through 52 weeks ]
  5. Percentage of participants with a ≥ 3-step improvement from baseline on the ETDRS-DRSS at Week 52 [ Time Frame: Week 52 ]
  6. Rate of participants developing a ≥ 3-step worsening from baseline on the ETDRS-DRSS through Week 52 [ Time Frame: Baseline up to 52 weeks ]
  7. Percentage of participants with a ≥ 2-step improvement from baseline on the ETDRS-DRSS over time [ Time Frame: Baseline up to Week 112 ]
  8. Percentage of participants with a ≥ 3-step improvement from baseline on the ETDRS-DRSS over time [ Time Frame: Baseline up to Week 112 ]
  9. Time to first development of either PDR, ASNV, or CI-DME [ Time Frame: Baseline up to Week 112 ]
  10. Time to first development of PDR or ASNV [ Time Frame: Baseline up to Week 112 ]
  11. Time to first development of CI-DME [ Time Frame: Baseline up to Week 112 ]
  12. Time to first development of a ≥ 2-step worsening from baseline on the ETDRS-DRSS [ Time Frame: Baseline up to Week 112 ]
  13. Time to first development of a ≥ 3-step worsening from baseline on the ETDRS-DRSS [ Time Frame: Baseline up to Week 112 ]
  14. Change from baseline in Best-Corrected Visual Acuity (BCVA) as measured on the ETDRS chart over time [ Time Frame: Baseline up to Week 112 ]
    A vision score of 20/20 vision is considered normal. A score of 20/200 is considered being legally blind.

  15. Percentage of participants who lose <15, < 10 and < 5 letters in BCVA from baseline over time [ Time Frame: Baseline up to Week 112 ]
  16. Percentage of participants with a BCVA score of 69 letters (20/40 approximate Snellen equivalent) or better over time [ Time Frame: Baseline up to Week 112 ]
  17. Change from baseline in CST as measured on SD-OCT over time [ Time Frame: Baseline up to Week 112 ]
  18. Change from baseline in total macular volume as measured on SD-OCT over time [ Time Frame: Baseline up to Week 112 ]
  19. Incidence and severity of ocular adverse events [ Time Frame: Baseline up to Week 112 ]
  20. Incidence and severity of non-ocular adverse events [ Time Frame: Baseline up to Week 112 ]
  21. Incidence, severity, and duration of adverse events of special interest [ Time Frame: Baseline up to Week 112 ]
  22. Incidence, severity, and duration of ocular adverse events of special interest during the postoperative period (≤ 37 days after initial implant insertion) and follow-up period (> 37 days after implant insertion surgery) [ Time Frame: Baseline up to Week 112 ]
  23. Serum concentration of ranibizumab observed over time [ Time Frame: Baseline up to Week 112 ]
  24. Pharmacokinetic (PK) parameter value area under the concentration- time curve [ Time Frame: Baseline up to Week 112 ]
  25. PK Parameter minimum serum concentration (Cmin) [ Time Frame: Baseline up to Week 112 ]
  26. PK parameter half-life (t1/2) after PDS implant insertion [ Time Frame: Baseline up to Week 112 ]
  27. Prevalence of anti-drug antibodies (ADAs) prior to study treatment and incidence of ADAs after study treatment [ Time Frame: Baseline up to Week 112 ]
  28. Prevalence of neutralizing antibodies at baseline and incidence of neutralizing antibodies during the study [ Time Frame: Baseline up to Week 112 ]
  29. Percentage of participants who do not undergo supplemental treatment with intravitreal ranibizumab within each refill-exchange interval [ Time Frame: Baseline up to Week 112 ]
  30. Percentage of participants with adverse device effects [ Time Frame: Baseline up to Week 112 ]
  31. Percentage of participants with serious adverse device effects [ Time Frame: Baseline up to Week 112 ]
  32. Percentage of participants with absence of intraretinal fluid, subretinal fluid or both (as measured in the central 1 mm subfield) over time [ Time Frame: Baseline up to Week 112 ]
  33. Percentage of participants who report preferring PDS treatment to intravitreal ranibizumab treatment, as measured by the PPPQ at Week 52 [ Time Frame: Week 52 ]
  34. Reported incidence of device deficiencies [ Time Frame: Baseline up to Week 52 ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥18 years at time of signing Informed Consent Form
  • Documented diagnosis of diabetes mellitus (Type 1 or Type 2)
  • HbA1c level of ≤12% within 2 months prior to screening or at screening

Inclusion Criteria for Study Eye

  • Moderately severe or severe NPDR (ETDRS-DRSS level 47 or 53)
  • BCVA score of ≥ 69 letters (20/40 approximate Snellen equivalent or better)

Exclusion Criteria:

  • Uncontrolled blood pressure
  • Cerebrovascular accident or myocardial infarction within 6 months prior to randomization
  • Atrial fibrillation diagnosis or worsening within 6 months prior to randomization
  • Current systemic treatment for a confirmed active systemic infection
  • Renal failure requiring renal transplant, hemodialysis, or peritoneal dialysis, or anticipated to require hemodialysis or peritoneal dialysis at any time during the study
  • History of other disease, other non-diabetic metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a condition that contraindicates the use of ranibizumab or surgical placement of the PDS implant; that might affect interpretation of the results of the study; or that renders the patient at high risk for treatment complications in the opinion of the investigator or Sponsor

Ocular Exclusion Criteria for Study Eye:

  • Presence of center-involved diabetic macular edema (defined as CST ≥325 µm)
  • Any intravitreal anti-VEGF treatment at any time prior to randomization
  • Any use of medicated intraocular implants, including Ozurdex® or Iluvien® implants at any time prior to randomization
  • Any intravitreal corticosteroid treatment at any time prior to randomization
  • Any periocular (e.g., subtenon) corticosteroid treatment at any time prior to randomization
  • Any PRP at any time prior to randomization
  • Any macular laser photocoagulation (such as micropulse and focal or grid laser) at any time prior to randomization
  • Active intraocular inflammation (grade trace or above)
  • Clinically significant abnormalities of the vitreous-retinal interface involving the macular area or disrupting the macular architecture, such as vitreous-retinal traction or epiretinal membrane (assessed by the investigator and confirmed by the central reading center)
  • Uncontrolled ocular hypertension or glaucoma and any such condition the investigator determines may require a glaucoma-filtering surgery during a participant's participation in the study
  • History of glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery
  • Any concurrent ocular condition (e.g., cataract, epiretinal membrane) that would require surgical intervention during the study to prevent or treat visual loss that might result from that condition
  • Any concurrent ocular condition (e.g., amblyopia, strabismus) that may affect interpretation of study results
  • History of other ocular diseases that gives reasonable suspicion of a disease or condition that contraindicates the use of ranibizumab, that might affect interpretation of study results, or that renders the participant at high risk for treatment complications

Ocular Exclusion Criteria for Either Eye

  • Suspected or active ocular or periocular infection of either eye
  • Any history uveitis including idiopathic, drug-associated or autoimmune-associated uveitis
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): NCT04503551


Locations
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Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
More Information
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT04503551    
Other Study ID Numbers: GR41675
First Posted: August 7, 2020    Key Record Dates
Last Update Posted: September 13, 2023
Last Verified: September 2023
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.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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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hoffmann-La Roche:
Port Delivery System; ranibizumab; Diabetic Retinopathy; anti-VEGF, nonproliferative diabetic retinopathy, retina, vision loss, retinal disease, eye disease
Additional relevant MeSH terms:
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Retinal Diseases
Diabetic Retinopathy
Eye Diseases
Diabetic Angiopathies
Vascular Diseases
Cardiovascular Diseases
Diabetes Complications
Diabetes Mellitus
 Endocrine System Diseases
Ranibizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents