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Safety and Pharmacokinetics of RTH258 in Subjects With Age-Related Macular Degeneration

Primary Purpose

Neovascular Age-Related Macular Degeneration

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Brolucizumab 3 mg/50 μL
Brolucizumab 6 mg/50 μL
Sponsored by
Alcon Research
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Neovascular Age-Related Macular Degeneration focused on measuring AMD, nAMD, wetAMD, Age-Related Macular Degeneration

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Provide written informed consent;
  • Active choroidal neovascularization (CNV) lesions secondary to AMD that affect the central subfield in the study eye;
  • Best Corrected Visual Acuity (BCVA) > 23 letters in the study eye at Baseline;
  • 50 years of age or older at the time of Screening.

Exclusion Criteria:

  • Any active ocular infection or inflammation;
  • Treatment with aflibercept (EYLEA®), bevacizumab (AVASTIN®), ranibizumab (LUCENTIS®), brolucizumab, or an investigational drug for neovascular AMD prior to enrollment in the study, as specified in protocol;
  • Ocular surgery in the study eye, as specified in protocol;
  • Uncontrolled glaucoma in the study eye, as specified in protocol;
  • Use of steroids in the study eye, as specified in protocol;
  • Medical conditions that may prevent study completion;
  • Pregnant or nursing (lactating) women;
  • Women of child-bearing potential unless using contraception;
  • Uncontrolled blood pressure, as specified in protocol;
  • Other protocol-specified exclusion criteria may apply.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Experimental

    Arm Label

    Brolucizumab 3 mg

    Brolucizumab 6 mg

    Arm Description

    Brolucizumab 3 mg/50 μL administered as an intravitreal injection 3 times at 4-week intervals with follow-up for 84 days from the initial injection

    Brolucizumab 6 mg/50 μL administered as an intravitreal injection 3 times at 4-week intervals with follow-up for 84 days from the initial injection

    Outcomes

    Primary Outcome Measures

    Maximum Analyte Serum Concentration [Cmax (ng/mL)]
    Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental pharmacokinetic (PK) method.
    Time to Reach Maximum Analyte Serum Concentration [Tmax (h)]
    Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental pharmacokinetic (PK) method.
    Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC0-tlast (ng*h/mL)]
    Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental pharmacokinetic (PK) method.
    Area Under the Concentration-time Curve From 0 to Infinity [AUC0-inf (ng*h/mL)]
    Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental pharmacokinetic (PK) method.
    Elimination Half-life in Serum [t1/2 (h)]
    Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental pharmacokinetic (PK) method.
    Concentration of RTH258 Obtained 24 Hours Post Day 0 Injection [C24hr (ng/mL)]
    Serum concentration at the specified collection time point was quantitated, where possible, using a validated immunoassay method. The data were analyzed using a noncompartmental pharmacokinetic (PK) method.
    Concentration of RTH258 Obtained 24 Hours Post Day 56 Injection [C24hr (ng/mL)]
    Serum concentration at the specified collection time point was quantitated, where possible, using a validated immunoassay method. The data were analyzed using a noncompartmental pharmacokinetic (PK) method.

    Secondary Outcome Measures

    Percentage of Subjects With Positive Anti-drug Antibody (ADA) Status (Test)
    A positive ADA status is defined as induced ADA status with ADA negative at predose and with a post-dose titer value increase of 2 or more dilutions at any time point or boosted ADA status with ADA positive at predose and a post-dose titer value increase by more than 3-fold (1 dilution) at any time point.

    Full Information

    First Posted
    July 22, 2015
    Last Updated
    May 31, 2018
    Sponsor
    Alcon Research
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02507388
    Brief Title
    Safety and Pharmacokinetics of RTH258 in Subjects With Age-Related Macular Degeneration
    Official Title
    A Randomized, Double Masked, Three Dose Safety and Pharmacokinetic Study of RTH258 Following Intravitreal (IVT) Injection in Subjects With Neovascular Age-Related Macular Degeneration
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2017
    Overall Recruitment Status
    Completed
    Study Start Date
    August 24, 2015 (Actual)
    Primary Completion Date
    September 6, 2016 (Actual)
    Study Completion Date
    September 6, 2016 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Alcon Research

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The purpose of this study is to assess the systemic pharmacokinetics (PK) and safety of 2 different doses of brolucizumab (3 milligrams (mg)/50 microliters (μL) and 6 mg/50 μL) when administered at 4-week intervals for a total of 3 intravitreal injections in subjects with neovascular age-related macular degeneration (AMD).
    Detailed Description
    This study has 2 arms with a 1:1 randomization. Randomization will be stratified by Japanese ethnicity. Half of the subjects in each arm will be of Japanese ethnicity. The other half of the subjects in each arm will be non-Japanese. Subjects in both arms will have visits at Screening, Day 0 (Baseline), Day 1 (24 hours post first injection), Day 3, Day 14, Day 21, Day 28, Day 56, Day 57 (24 hours post the injection on Day 56) and Day 84.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Neovascular Age-Related Macular Degeneration
    Keywords
    AMD, nAMD, wetAMD, Age-Related Macular Degeneration

    7. Study Design

    Primary Purpose
    Other
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    51 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Brolucizumab 3 mg
    Arm Type
    Experimental
    Arm Description
    Brolucizumab 3 mg/50 μL administered as an intravitreal injection 3 times at 4-week intervals with follow-up for 84 days from the initial injection
    Arm Title
    Brolucizumab 6 mg
    Arm Type
    Experimental
    Arm Description
    Brolucizumab 6 mg/50 μL administered as an intravitreal injection 3 times at 4-week intervals with follow-up for 84 days from the initial injection
    Intervention Type
    Drug
    Intervention Name(s)
    Brolucizumab 3 mg/50 μL
    Other Intervention Name(s)
    RTH258, ESBA1008
    Intervention Description
    Administered as an intravitreal injection
    Intervention Type
    Drug
    Intervention Name(s)
    Brolucizumab 6 mg/50 μL
    Other Intervention Name(s)
    RTH258, ESBA1008
    Intervention Description
    Administered as an intravitreal injection
    Primary Outcome Measure Information:
    Title
    Maximum Analyte Serum Concentration [Cmax (ng/mL)]
    Description
    Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental pharmacokinetic (PK) method.
    Time Frame
    Day 0 (predose), 6 hr, 24 hr, 72 hr, 168 hr, 336 hr, 504 hr, 672 hr
    Title
    Time to Reach Maximum Analyte Serum Concentration [Tmax (h)]
    Description
    Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental pharmacokinetic (PK) method.
    Time Frame
    Day 0 (predose), 6 hr, 24 hr, 72 hr, 168 hr, 336 hr, 504 hr, 672 hr
    Title
    Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC0-tlast (ng*h/mL)]
    Description
    Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental pharmacokinetic (PK) method.
    Time Frame
    Day 0 (predose), 6 hr, 24 hr, 72 hr, 168 hr, 336 hr, 504 hr, 672 hr
    Title
    Area Under the Concentration-time Curve From 0 to Infinity [AUC0-inf (ng*h/mL)]
    Description
    Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental pharmacokinetic (PK) method.
    Time Frame
    Day 0 (predose), 6 hr, 24 hr, 72 hr, 168 hr, 336 hr, 504 hr, 672 hr
    Title
    Elimination Half-life in Serum [t1/2 (h)]
    Description
    Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental pharmacokinetic (PK) method.
    Time Frame
    Day 0 (predose), 6 hr, 24 hr, 72 hr, 168 hr, 336 hr, 504 hr, 672 hr
    Title
    Concentration of RTH258 Obtained 24 Hours Post Day 0 Injection [C24hr (ng/mL)]
    Description
    Serum concentration at the specified collection time point was quantitated, where possible, using a validated immunoassay method. The data were analyzed using a noncompartmental pharmacokinetic (PK) method.
    Time Frame
    Day 1
    Title
    Concentration of RTH258 Obtained 24 Hours Post Day 56 Injection [C24hr (ng/mL)]
    Description
    Serum concentration at the specified collection time point was quantitated, where possible, using a validated immunoassay method. The data were analyzed using a noncompartmental pharmacokinetic (PK) method.
    Time Frame
    Day 57
    Secondary Outcome Measure Information:
    Title
    Percentage of Subjects With Positive Anti-drug Antibody (ADA) Status (Test)
    Description
    A positive ADA status is defined as induced ADA status with ADA negative at predose and with a post-dose titer value increase of 2 or more dilutions at any time point or boosted ADA status with ADA positive at predose and a post-dose titer value increase by more than 3-fold (1 dilution) at any time point.
    Time Frame
    Day 0 (predose), Day 28, Day 84

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    50 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Provide written informed consent; Active choroidal neovascularization (CNV) lesions secondary to AMD that affect the central subfield in the study eye; Best Corrected Visual Acuity (BCVA) > 23 letters in the study eye at Baseline; 50 years of age or older at the time of Screening. Exclusion Criteria: Any active ocular infection or inflammation; Treatment with aflibercept (EYLEA®), bevacizumab (AVASTIN®), ranibizumab (LUCENTIS®), brolucizumab, or an investigational drug for neovascular AMD prior to enrollment in the study, as specified in protocol; Ocular surgery in the study eye, as specified in protocol; Uncontrolled glaucoma in the study eye, as specified in protocol; Use of steroids in the study eye, as specified in protocol; Medical conditions that may prevent study completion; Pregnant or nursing (lactating) women; Women of child-bearing potential unless using contraception; Uncontrolled blood pressure, as specified in protocol; Other protocol-specified exclusion criteria may apply.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Alcon, A Novartis Division
    Organizational Affiliation
    Alcon, A Novartis Division
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided
    IPD Sharing Plan Description
    Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

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    Safety and Pharmacokinetics of RTH258 in Subjects With Age-Related Macular Degeneration

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