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A Study of Faricimab (RO6867461) in Participants With Center-involving Diabetic Macular Edema (BOULEVARD)

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: NCT02699450
Recruitment Status : Completed
First Posted : March 4, 2016
Last Update Posted : September 17, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE March 1, 2016
First Posted Date  ICMJE March 4, 2016
Last Update Posted Date September 17, 2019
Actual Study Start Date  ICMJE April 27, 2016
Actual Primary Completion Date September 15, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 29, 2017)
Mean Change from Baseline in BCVA Letter Score at Week 24, in Treatment-Naive Participants [ Time Frame: Baseline, Week 24 ]
BVCA letter score will be assessed using modified Early Treatment Diabetic Retinopathy Study (ETDRS) charts.
Original Primary Outcome Measures  ICMJE
 (submitted: March 1, 2016)
  • Mean change from baseline in BCVA at week 24 using early treatment diabetic retinopathy study (ETDRS) modified charts [ Time Frame: Baseline, Week 24 ]
  • Clearance of RO6867461 [ Time Frame: Pre-dose on Days 1, 28, 84, 140, and 168; post-dose on Days 7, 182, and 196 or early termination ]
  • Volume of distribution of RO6867461 [ Time Frame: Pre-dose on Days 1, 28, 84, 140, and 168; post-dose on Days 7, 182, and 196 or early termination ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 9, 2019)
  • Percentage of Participants who Gain ≥ 15 Letters in BCVA Letter Score [ Time Frame: Baseline up to Week 24 ]
    BVCA letter score will be assessed using modified ETDRS charts.
  • Percentage of Participants with BCVA ≥ 69 Letters (20/40 or Better) in BCVA Letter Score [ Time Frame: Week 24 ]
    BVCA letter score will be assessed using modified ETDRS charts.
  • Percentage of Participants With BCVA ≥ 84 Letters (20/20 or Better) in BCVA Letter Score [ Time Frame: Week 24 ]
    BVCA letter score will be assessed using modified ETDRS charts.
  • Mean Change from Baseline in Foveal Center Point Thickness at Week 24 [ Time Frame: Baseline, Week 24 ]
    Foveal center point thickness will be measured using spectral domain optical coherence tomography (SD-OCT).
  • Mean Change from Baseline in Mean CST at Week 24 [ Time Frame: Baseline, Week 24 ]
    CST will be measured using SD-OCT.
  • Percentage of Participants with Resolution of Subretinal and Intraretinal Fluid [ Time Frame: Week 24 ]
    Resolution of subretinal and intraretinal fluid will be measured using SD-OCT.
  • Percentage of Participants with Resolution of Leakage at the Macula [ Time Frame: Week 24 ]
    Resolution of leakage at the macula will be measured using fundus fluorescein angiography (FFA).
  • Change from Baseline in the Size of the Foveal Avascular Zone at Week 24 [ Time Frame: Baseline, Week 24 ]
    Size of the foveal avascular zone will be measured using FFA.
  • Change from Baseline in VEGF Plasma [ Time Frame: Up to 36 Weeks ]
  • Change from Baseline in Angiopoietin-2 (Ang-2) Plasma Levels [ Time Frame: Up to 36 Weeks ]
  • Maximum Observed Plasma Concentration (Cmax) of Faricimab [ Time Frame: Up to 36 Weeks ]
  • Area Under the Plasma Concentration-Time Curve from Time Zero to Extrapolated Infinite Time [AUC (0-inf)] of Faricimab [ Time Frame: Up to 36 Weeks ]
  • Area Under the Plasma Concentration-Time Curve from Time Zero to End of Dosing Interval [AUC (0-tau)] of Faricimab [ Time Frame: Up to 36 Weeks ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) of Faricimab [ Time Frame: Up to 36 Weeks ]
  • Plasma Decay Half-Life (t1/2) of Faricimab [ Time Frame: Up to 36 Weeks ]
  • Percentage of Participants With Adverse Events (AEs) [ Time Frame: Baseline up to Week 36 (or early termination) ]
  • Percentage of Participants With Anti-Faricimab Antibodies [ Time Frame: Baseline up to Week 36 (or early termination) ]
  • Apparent Plasma Clearance of Faricimab [ Time Frame: Up to 36 Weeks ]
  • Apparent Plasma Volume of Faricimab [ Time Frame: Up to 36 Weeks ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 1, 2016)
  • Percentage of participants gaining greater than or equals (>/=) 15 letters from baseline BCVA at Week 24 [ Time Frame: Baseline, and Week 24 ]
  • Percentage of participants with BCVA >/=69 letters (20/40 or better) at Week 24 [ Time Frame: Week 24 ]
  • Percentage of participants with BCVA >/=84 letters (20/20 or better) at Week 24 [ Time Frame: Week 24 ]
  • Mean change from baseline in BCVA at Week 28 [ Time Frame: Baseline, and Week 28 ]
  • Mean change from baseline in foveal center point thickness at Week 24 and 28, as measures by spectral domain optical coherence tomography (SD-OCT) [ Time Frame: Baseline, Weeks 24, and 28 ]
  • Mean change from baseline in mean central subfield thickness (CST) at Week 24 and 28, as measures by SD-OCT [ Time Frame: Baseline, Weeks 24, and 28 ]
  • Percentage of participants with resolution of subretinal and intraretinal fluid at Week 24 and 28, as measures by SD-OCT [ Time Frame: Weeks 24, and 28 ]
  • Percentage of participants with resolution of leakage at the macula at Week 24, as measures by fundus fluorescein angiography (FFA) [ Time Frame: Week 24 ]
  • Change from baseline in the size of the foveal avascular zone at Week 24, as measures by FFA [ Time Frame: Baseline and Week 24 ]
  • Change from baseline in plasma levels of vascular endothelial growth factor (VEGF) [ Time Frame: Baseline, Weeks 1, 4, 12, 24, 26, and 28 or early termination ]
  • Change from baseline in plasma levels of angiopoietin-2 (Ang-2) [ Time Frame: Baseline, Weeks 1, 4, 12, 24, 26, and 28 or early termination ]
  • Maximum Observed Plasma Concentration (Cmax) of RO6867461 [ Time Frame: Pre-dose on Days 1, 28, 84, 140, and 168; post-dose on Days 7, 182, and 196 or early termination ]
  • Area Under the Plasma Concentration-Time Curve from Time Zero to Extrapolated Infinite Time [AUC (0-inf)] of RO6867461 [ Time Frame: Pre-dose on Days 1, 28, 84, 140, and 168; post-dose on Days 7, 182, and 196 or early termination ]
  • Area Under the Plasma Concentration-Time Curve from Time Zero to End of Dosing Interval [AUC (0-tau)] of RO6867461 [ Time Frame: Pre-dose on Days 1, 28, 84, 140, and 168; post-dose on Days 7, 182, and 196 or early termination ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) of RO6867461 [ Time Frame: Pre-dose on Days 1, 28, 84, 140, and 168; post-dose on Days 7, 182, and 196 or early termination ]
  • Plasma Decay Half-Life (t1/2) of RO6867461 [ Time Frame: Pre-dose on Days 1, 28, 84, 140, and 168; post-dose on Days 7, 182, and 196 or early termination ]
  • Number of participants with adverse events [ Time Frame: Baseline up to Week 28 or early termination ]
  • Number of participants with anti-RO6867461 antibodies [ Time Frame: Baseline, Weeks 1, 4, 12, 20, 24, 26, and 28 or early termination ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Faricimab (RO6867461) in Participants With Center-involving Diabetic Macular Edema
Official Title  ICMJE A Multiple-Center, Multiple-Dose, Randomized, Active Comparator−Controlled, Double-Masked, Parallel Group, 36-Week Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Efficacy of RO6867461 Administered Intravitreally in Patients With Diabetic Macular Edema
Brief Summary This is a multiple-center, multiple-dose, randomized, active comparator-controlled, double-masked, three parallel group, 36-week study in participants with center-involving diabetic macular edema (DME). Only one eye will be selected as the study eye. Where both eyes meet all eligibility criteria, the eye with the worse best corrected visual acuity (BCVA) will be defined as the study eye. The study will consist of a treatment period (20 weeks) and an observational period (up to 16 weeks). Treatment naive participants will be randomized in a 1:1:1 ratio to one of the Arms A, B and C, respectively. Participants previously treated with intravitreal (IVT) anti-vascular endothelial growth factor (VEGF) will be randomized in a 1:1 ratio to Arms A and C.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Diabetic Macular Edema
Intervention  ICMJE
  • Drug: Faricimab
    Faricimab will be administered by IVT injection in the study eye.
    Other Names:
    • RO6867461
    • RG7716
  • Drug: Ranibizumab
    Ranibizumab will be administered by IVT injection in the study eye.
    Other Name: Lucentis
Study Arms  ICMJE
  • Active Comparator: Arm A: 0.3 mg Ranibizumab
    Participants will receive 0.3 milligrams (mg) ranibizumab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant meets pre-specified criteria the participant will receive a single dose of 0.3 mg ranibizumab and exit the study.
    Intervention: Drug: Ranibizumab
  • Experimental: Arm B: 1.5 mg Faricimab
    Participants will receive 1.5 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant meets pre-specified criteria the participant will receive a single dose of 0.3 mg ranibizumab and exit the study.
    Intervention: Drug: Faricimab
  • Experimental: Arm C: 6 mg Faricimab
    Participants will receive 6 mg faricimab every fourth week up to Week 20, for a total of 6 administrations, followed by an observational period up to Week 36. If a participant meets pre-specified criteria the participant will receive a single dose of 0.3 mg ranibizumab and exit the study.
    Intervention: Drug: Faricimab
Publications * Sahni J, Patel SS, Dugel PU, Khanani AM, Jhaveri CD, Wykoff CC, Hershberger VS, Pauly-Evers M, Sadikhov S, Szczesny P, Schwab D, Nogoceke E, Osborne A, Weikert R, Fauser S. Simultaneous Inhibition of Angiopoietin-2 and Vascular Endothelial Growth Factor-A with Faricimab in Diabetic Macular Edema: BOULEVARD Phase 2 Randomized Trial. Ophthalmology. 2019 Aug;126(8):1155-1170. doi: 10.1016/j.ophtha.2019.03.023. Epub 2019 Mar 21.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 9, 2019)
229
Original Estimated Enrollment  ICMJE
 (submitted: March 1, 2016)
150
Actual Study Completion Date  ICMJE December 14, 2017
Actual Primary Completion Date September 15, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Macular edema associated with diabetic retinopathy
  • Decreased visual acuity attributable primarily to DME
  • Diagnosis of diabetes mellitus

Exclusion Criteria:

  • High risk proliferative diabetic retinopathy
  • Cataract surgery within 3 months of Baseline, or any other previous intraocular surgery
  • Uncontrolled glaucoma
  • Current or history of ocular disease in the study eye other than DME
  • Major illness or major surgical procedure within 1 month prior to Day 1
  • Uncontrolled blood pressure
  • Glycosylated hemoglobin (HbA1c) greater than (>) 12 percent (%) at screening
  • Untreated diabetes mellitus or initiation of oral anti-diabetic medication or insulin within 4 months prior to Day 1
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02699450
Other Study ID Numbers  ICMJE BP30099
RG7716 ( Other Identifier: Roche theme number )
Has Data Monitoring Committee No
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  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP