BURGUNDY: Study of RO7250284 in Participants With Neovascular Age-Related Macular Degeneration

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04567303
Collaborator
(none)
190
10
5
60.7
19
0.3

Study Details

Study Description

Brief Summary

This is a first in-human study to investigate the safety, tolerability and efficacy of RO7250284 administered through intravitreal (IVT) injections and via the Port Delivery System in participants with neovascular age-related macular degeneration (nAMD)

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
190 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Part 1 of the study will be an open-label multiple ascending dose study, followed by subsequent assignment to 2 groups in Part 2. Part 3 will enroll new participants to compare the efficacy of RO7250284 PD implant versus ranibizumab released via the PD implant.Part 1 of the study will be an open-label multiple ascending dose study, followed by subsequent assignment to 2 groups in Part 2. Part 3 will enroll new participants to compare the efficacy of RO7250284 PD implant versus ranibizumab released via the PD implant.
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:
Part 1: Visual Acuity examiner; Part 2: Participant, Investigator and Sponsor; Part 3: Participant and Investigator
Primary Purpose:
Treatment
Official Title:
A Three-Part, Phase I Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Efficacy of RO7250284 Following Intravitreal Administration of Multiple Ascending Doses and Sustained Delivery From the Port Delivery System in Patients With Neovascular Age-Related Macular Degeneration
Actual Study Start Date :
Oct 28, 2020
Anticipated Primary Completion Date :
Nov 19, 2025
Anticipated Study Completion Date :
Nov 19, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Part 1: Intravitreal Injections

RO7250284 administered in ascending dose levels through IVT injections.

Drug: RO7250284
Part 1: multiple ascending doses by intravitreal injection. Each participant will receive RO7250284 at a constant volume of 50 microliter in the study eye. Part 2: participants will be randomized to one of two dose levels of RO7250284 in the PDS implant.

Experimental: Part 2: Port Delivery System with High Dose

RO7250284 administered at a high dose through the PDS implant.

Drug: RO7250284
Part 1: multiple ascending doses by intravitreal injection. Each participant will receive RO7250284 at a constant volume of 50 microliter in the study eye. Part 2: participants will be randomized to one of two dose levels of RO7250284 in the PDS implant.

Experimental: Part 2: Port Delivery System with Low Dose

RO7250284 administered at a low dose through the PDS implant.

Drug: RO7250284
Part 1: multiple ascending doses by intravitreal injection. Each participant will receive RO7250284 at a constant volume of 50 microliter in the study eye. Part 2: participants will be randomized to one of two dose levels of RO7250284 in the PDS implant.

Experimental: Part 3: Port Delivery System with High Dose

RO7250284 administered at a high dose through the PDS implant.

Drug: RO7250284
Part 1: multiple ascending doses by intravitreal injection. Each participant will receive RO7250284 at a constant volume of 50 microliter in the study eye. Part 2: participants will be randomized to one of two dose levels of RO7250284 in the PDS implant.

Active Comparator: Part 3: Port Delivery System with Ranibizumab

100 mg/mL of ranibizumab administered through the PDS implant.

Drug: Ranibizumab
Participants will receive 100 mg/mL of ranibizumab through the PDS
Other Names:
  • Lucentis
  • Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants with Ocular and Systemic (Nonocular) Adverse Events [Part 1: Baseline up to Week 24; Part 2: Baseline up to Month 12; Part 3: Baseline up to Month 9.]

    2. Percentage of Participants with Adverse Events of Special Interest (AESIs) including Ocular AESIs [Part 1: Baseline up to Week 24; Part 2: Baseline up to Month 12; Part 3: Baseline up to Month 9.]

    3. Percentage of Participants with Adverse Events of Special Interest (AESIs) including Ocular AESIs during the Postoperative and Follow-up periods [Part 1: Baseline up to Week 24; Part 2: Baseline up to Month 12; Part 3: Baseline up to Month 9.]

    4. Duration of Adverse Events of Special Interest (AESIs) including Ocular AESIs [Part 1: Baseline up to Week 24; Part 2: Baseline up to Month 12; Part 3: Baseline up to Month 9.]

    5. Duration of Adverse Events of Special Interest (AESIs) including Ocular AESIs during the Postoperative and Follow-up periods [Part 1: Baseline up to Week 24; Part 2: Baseline up to Month 12; Part 3: Baseline up to Month 9.]

    6. Percentage of Participants with Adverse Device Effects (ADEs) [Part 1: Baseline up to Week 24; Part 2: Baseline up to Month 12; Part 3: Baseline up to Month 9.]

    7. Duration of Adverse Device Effects (ADEs) [Part 1: Baseline up to Week 24; Part 2: Baseline up to Month 12; Part 3: Baseline up to Month 9.]

    8. Percentage of Participants with Anticipated Serious ADEs (ASADEs) [Part 1: Baseline up to Week 24; Part 2: Baseline up to Month 12; Part 3: Baseline up to Month 9.]

    9. Duration of Anticipated Serious ADEs (ASADEs) [Part 1: Baseline up to Week 24; Part 2: Baseline up to Month 12; Part 3: Baseline up to Month 9.]

    10. Change from Baseline in Early Treatment Diabetic Retinopathy Study - Best Corrected Visual Acuity (ETDRS-BCVA) Score [Part 3: Baseline (baseline visit, before implant insertion) to Week 36]

      ETDRS-BCVA will be used to quantify visual acuity. BCVA is measured using an eye chart and is reported as the number of letters read correctly using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved.

    Secondary Outcome Measures

    1. Maximum Observed Concentration (Cmax) of RO7250284 in Blood and Aqueous Humor (AH) [Part 1: Baseline up to Week 24; Part 2: Baseline up to Month 36; Part 3: Baseline up to Month 36.]

    2. Time of Maximum Concentration Observed (Tmax) of RO7250284 in Blood and AH [Part 1: Baseline up to Week 24; Part 2: Baseline up to Month 36; Part 3: Baseline up to Month 36.]

    3. Concentration at the End of a Dosing Interval before the Next Dose Administration (Ctrough) of RO7250284 in Blood and AH [Part 1: Baseline up to Week 24; Part 2: Baseline up to Month 36; Part 3: Baseline up to Month 36.]

    4. Area Under the Curve (AUC) of RO7250284 in Blood and AH [Part 1: Baseline up to Week 24; Part 2: Baseline up to Month 36; Part 3: Baseline up to Month 36.]

    5. Change from Baseline in Early Treatment Diabetic Retinopathy Study - Best Corrected Visual Acuity (ETDRS-BCVA) Score [Part 3: Baseline (baseline visit, before implant insertion) to Week 48]

      ETDRS-BCVA will be used to quantify visual acuity. BCVA is measured using an eye chart and is reported as the number of letters read correctly using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved.

    6. Percentage of Participants who did not meet Supplemental Treatment Criteria for the PDS implant with RO7250284 [Week 28 and Week 32]

    7. Percentage of Participants who Gain or Lose ≥15, ≥10 or ≥5 letters in ETDRS-BCVA score from Baseline [Week 36]

      ETDRS-BCVA will be used to quantify visual acuity. BCVA is measured using an eye chart and is reported as the number of letters read correctly using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved.

    8. Change from Baseline in Center Point Thickness (CPT) [Baseline to Week 36]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    50 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Part 1, Part 2 and Part 3 Inclusion Criteria:
    • Willing to allow AH collection.
    Part 1 and Part 2 Ocular Inclusion Criteria for Study Eye:
    • Choroidal neovascularization (CNV) exclusively due to age-related macular degeneration (AMD).

    • Anti-VEGF IVT treatment-naïve, or pre-treated with anti-VEGF no less than two months prior to Day 1.

    • Sufficiently clear ocular media and adequate pupillary dilatation to allow for analysis and grading by the central reading center of fundus photography (FP), fluorescein angiography (FA), fundus autofluorescence (FAF), and spectral domain optical coherence tomography (SD-OCT) images.

    • Decreased best corrected visual acuity (BCVA) attributable primarily to neovascular AMD (nAMD), with BCVA letter score of 78 to 34 letters (inclusive) on early treatment diabetic retinopathy study (ETDRS)-like charts at screening. In case both eyes of a participant are eligible, the eye with the lower BCVA score should become the study eye.

    Part 3 Ocular Inclusion Criteria for Study Eye:
    • CNV exclusively due to AMD.

    • Diagnosis of nAMD within nine months prior to the screening visit.

    • Previous treatment with at least two anti-VEGF IVT for nAMD.

    • Demonstrated response to prior IVT anti-VEGF treatment since diagnosis.

    • Availability of historical visual acuity (VA) data prior to the first anti-VEGF treatment for nAMD.

    • Sufficiently clear ocular media and adequate pupillary dilatation to allow for analysis and grading.

    • BCVA letter score of 34 letters (inclusive) or better on ETDRS-like charts.

    Exclusion Criteria for Study Eye:
    • History of vitrectomy surgery, submacular surgery, other intraocular surgery, or any planned surgical intervention during the study period.

    • Cataract surgery without complications within three months preceding the screening visit or planned during the study period.

    • Aphakia or absence of the posterior capsule.

    • Prior macular treatment with verteporfin, external beam radiation therapy, transpupillary thermotherapy, or any type of laser photocoagulation.

    • Prior treatment with IVT corticosteroids or implant (e.g., triamcinolone, ozurdex, iluvien).

    • Subretinal hemorrhage >50% of the total lesion area and/or involving the fovea.

    • Subfoveal fibrosis or subfoveal atrophy.

    • Retinal pigment epithelial tear involving the macula.

    • History of vitreous hemorrhage, rhegmatogenous retinal detachment, glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery, and corneal transplant.

    • History of rhegmatogenous retinal tears or peripheral retinal breaks within three months prior to the screening visit.

    • Actual or history of myopia >-8 diopters.

    • Uncontrolled ocular hypertension or glaucoma (defined as IOP >25 mm Hg or a cup to disc ration >0.8, despite treatment with antiglaucoma medication) and any such condition the Investigator determines may require a glaucoma-filtering surgery during a participant's participation in the study.

    • Concurrent intraocular conditions (e.g., cataract, diabetic retinopathy, epiretinal membrane with traction, macular hole).

    Exclusion Criteria for Fellow Eye

    • BCVA letter score using ETDRS charts of < 34 letters.

    • Treatment with anti-VEGF agents within one month prior to Day 1 (for Part 1) or prior to the randomization visit (Part 3).

    Exclusion Criteria for Either Eye

    • CNV due to causes other than nAMD, such as ocular histoplasmosis, trauma, pathological myopia, angioid streaks, choroidal rupture, uveitis or central serous chorioretinopathy.

    • Prior participation in a clinical trial involving anti-VEGF drugs within six months prior to the screening visit, other than ranibizumab, aflibercept, or faricimab.

    • Active intraocular inflammation (grade trace or above), infectious conjunctivitis, keratitis, scleritis, or endophthalmitis.

    • History of uveitis, including history of any intraocular inflammation following intravitreal anti-VEGF injections.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Barnet Dulaney Perkins Eye Center Mesa Arizona United States 85206
    2 Retina Vitreous Assoc of FL Saint Petersburg Florida United States 33711
    3 Southern Vitreoretinal Assoc Tallahassee Florida United States 32308
    4 Southeast Retina Center Augusta Georgia United States 30909
    5 Sierra Eye Associates Reno Nevada United States 89502
    6 Envision Ocular, LLC Bloomfield New Jersey United States 07003
    7 Mid Atlantic Retina - Wills Eye Hospital Cherry Hill New Jersey United States 08034
    8 Tennessee Retina PC. Nashville Tennessee United States 37203
    9 Austin Research Center for Retina Austin Texas United States 78705
    10 Retina Consultants of Texas Bellaire Texas United States 77401

    Sponsors and Collaborators

    • Hoffmann-La Roche

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT04567303
    Other Study ID Numbers:
    • BP41670
    First Posted:
    Sep 28, 2020
    Last Update Posted:
    Aug 8, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 8, 2022