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A Study to Evaluate Subcutaneous Zilucoplan in Pediatric Participants With Generalized Myasthenia Gravis

Primary Purpose

Generalized Myasthenia Gravis

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Zilucoplan
Sponsored by
UCB Biopharma SRL
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Generalized Myasthenia Gravis focused on measuring RA101495, gMG, generalized myasthenia gravis, zilucoplan, pediatric, MG0014

Eligibility Criteria

2 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Participant must be 2 to <18 years of age at the time of signing the Informed consent/assent according to local regulation Participant has a diagnosis of generalized myasthenia gravis (gMG) confirmed by a prior positive serologic test result to acetylcholine receptor (AChR) prior to Screening Participant meets the criteria as defined by the Myasthenia Gravis Foundation of America (MGFA) Clinical Classification II to IV at Screening Participants with gMG, including: An MG-activities of daily living (MG-ADL) total score of 6 or more in adolescents from 12 years to <18 years of age at Screening Documented weakness in at least 1 limb, neck, or bulbar muscle in children from 2 years to <12 years of age at Screening Documented vaccination against meningococcal infections within 3 years prior to study start. If not fully vaccinated, participants must receive appropriate prophylactic antibiotic treatment until at least 2 weeks after the initial dose of vaccine(s) Exclusion Criteria: Participant has known positive serology for muscle-specific kinase Participant has any medical or psychiatric condition that, in the opinion of the Investigator, could jeopardize or would compromise the participant's ability to participate in this study Participant has had a thymectomy within 6 months prior to Baseline Participant has minimal Manifestation Status of MG based on the clinical judgement of the Investigator Current or recent systemic infection within 2 weeks prior to Baseline or infection requiring intravenous antibiotics within 4 weeks prior to Baseline

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Zilucoplan Arm

    Arm Description

    Study participants will receive zilucoplan in pre-defined dose based on their weight.

    Outcomes

    Primary Outcome Measures

    Plasma concentrations of zilucoplan (ZLP) sampled at Week 4 (Day 29)
    Blood samples will be collected for measurement of plasma concentrations of ZLP on Day 29 predose.
    Change from Baseline in sheep red blood cell (sRBC) lysis at Week 4 (Day 29)
    Samples for measurement of sRBC lysis will be collected on Day 29 predose.
    Change from Baseline in complement component 5 (C5) levels at Week 4 (Day 29)
    Samples for measurement of C5 will be collected on Day 29 predose.

    Secondary Outcome Measures

    Occurence of treatment-emergent adverse events (TEAEs) during the course of the study
    An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
    Occurrence of treatment-emergent serious adverse events (TESAEs)
    A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose: Results in death Is life-threatening Requires inpatient hospitalization or prolongation of existing hospitalization Results in persistent disability/incapacity Is a congenital anomaly/birth defect Important medical events
    Occurrence of TEAEs leading to permanent withdrawal of investigational medicinal product (IMP)
    An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. AEs leading to permanent withdrawal of study medication.
    Occurrence of treatment-emergent infections
    Percentage of participants who experienced treatment-emergent infections as adverse events. An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment.
    Occurrence of antidrug antibody (ADA) and anti- polyethylene glycol (PEG) antibodies at Week 4 (Day 29)
    ADA and anti-PEG antibodies will be evaluated in serum samples.
    Change in MG-activities of daily living (MG-ADL) score from Baseline to Week 4 (Day 29).
    The MG-ADL score is an 8-item patient-reported outcome (PRO) instrument. The MG-ADL targets symptoms and disability across ocular, bulbar, respiratory, and axial symptoms. The item responses are scored from 0 to 3, and the total score of MG-ADL is the sum of the 8 items and ranges from 0 to 24, with a higher score indicating more disability.
    Change in Quantitative MG (QMG) score from Baseline to Week 4 (Day 29)
    QMG score is a standardized and validated quantitative strength scoring system that was developed specifically for MG. The QMG total score is obtained by summing the responses to each individual item (13 items; Responses: None=0, Mild=1, Moderate=2, Severe=3). The score ranges from 0 to 39, with lower scores indicating lower disease activity.
    Myasthenia Gravis Foundation of America Post-Interventional Status (MGFA-PIS) at Week 4 (Day 29)
    The MGFA-PIS is a physician-determined assessment of clinical symptoms of MG after initiation of MG specific therapy. For the purpose of the current study, Minimal Manifestation will be determined at each scheduled time point after treatment initiation (rather than after 1 year). Change in status (improved, unchanged, worse, exacerbation, or died of MG) will also be determined.
    Change in Pediatric Quality of Life Inventory (PedsQoL), Version 4 domain scores from Baseline to Week 4 (Day 29)
    The PedsQoL generic core scale (Version 4) is a validated instrument that is suitable for use with pediatric populations. PedsQoL generic core scales assess Physical Functioning, Emotional Functioning, Social Functioning, and School Functioning. The scale has 23 items with a score range of 0 to 4. Following transformation, the score range of each domain as well as the total score is 0-100 with higher scores indicating higher HRQoL.

    Full Information

    First Posted
    September 20, 2023
    Last Updated
    September 20, 2023
    Sponsor
    UCB Biopharma SRL
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06055959
    Brief Title
    A Study to Evaluate Subcutaneous Zilucoplan in Pediatric Participants With Generalized Myasthenia Gravis
    Official Title
    A Multicenter Open-Label, Uncontrolled Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety, Tolerability, and Activity of Zilucoplan in Pediatric Study Participants From 2 to Less Than 18 Years of Age With Acetylcholine Receptor Antibody Positive Generalized Myasthenia Gravis
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    September 29, 2023 (Anticipated)
    Primary Completion Date
    October 26, 2026 (Anticipated)
    Study Completion Date
    December 4, 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    UCB Biopharma SRL

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The purpose of this study is to assess the pharmacokinetics, pharmacodynamics, safety, tolerability, immunogenicity and activity of zilucoplan (ZLP) in pediatric study participants with generalized myasthenia gravis (gMG).

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Generalized Myasthenia Gravis
    Keywords
    RA101495, gMG, generalized myasthenia gravis, zilucoplan, pediatric, MG0014

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2, Phase 3
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    8 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Zilucoplan Arm
    Arm Type
    Experimental
    Arm Description
    Study participants will receive zilucoplan in pre-defined dose based on their weight.
    Intervention Type
    Drug
    Intervention Name(s)
    Zilucoplan
    Other Intervention Name(s)
    RA101495
    Intervention Description
    Zilucoplan will be administered subcutaneously to pediatric study participants.
    Primary Outcome Measure Information:
    Title
    Plasma concentrations of zilucoplan (ZLP) sampled at Week 4 (Day 29)
    Description
    Blood samples will be collected for measurement of plasma concentrations of ZLP on Day 29 predose.
    Time Frame
    Week 4 (Day 29)
    Title
    Change from Baseline in sheep red blood cell (sRBC) lysis at Week 4 (Day 29)
    Description
    Samples for measurement of sRBC lysis will be collected on Day 29 predose.
    Time Frame
    Week 4 (Day 29)
    Title
    Change from Baseline in complement component 5 (C5) levels at Week 4 (Day 29)
    Description
    Samples for measurement of C5 will be collected on Day 29 predose.
    Time Frame
    Week 4 (Day 29)
    Secondary Outcome Measure Information:
    Title
    Occurence of treatment-emergent adverse events (TEAEs) during the course of the study
    Description
    An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
    Time Frame
    From Baseline (Day 1) to Safety-Follow-Up Visit (up to Week 15)
    Title
    Occurrence of treatment-emergent serious adverse events (TESAEs)
    Description
    A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose: Results in death Is life-threatening Requires inpatient hospitalization or prolongation of existing hospitalization Results in persistent disability/incapacity Is a congenital anomaly/birth defect Important medical events
    Time Frame
    From Baseline (Day 1) to Safety-Follow-Up Visit (up to Week 15)
    Title
    Occurrence of TEAEs leading to permanent withdrawal of investigational medicinal product (IMP)
    Description
    An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. AEs leading to permanent withdrawal of study medication.
    Time Frame
    From Baseline (Day 1) to Safety-Follow-Up Visit (up to Week 15)
    Title
    Occurrence of treatment-emergent infections
    Description
    Percentage of participants who experienced treatment-emergent infections as adverse events. An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment.
    Time Frame
    From Baseline (Day 1) to Safety-Follow-Up Visit (up to Week 15)
    Title
    Occurrence of antidrug antibody (ADA) and anti- polyethylene glycol (PEG) antibodies at Week 4 (Day 29)
    Description
    ADA and anti-PEG antibodies will be evaluated in serum samples.
    Time Frame
    Week 4 (Day 29)
    Title
    Change in MG-activities of daily living (MG-ADL) score from Baseline to Week 4 (Day 29).
    Description
    The MG-ADL score is an 8-item patient-reported outcome (PRO) instrument. The MG-ADL targets symptoms and disability across ocular, bulbar, respiratory, and axial symptoms. The item responses are scored from 0 to 3, and the total score of MG-ADL is the sum of the 8 items and ranges from 0 to 24, with a higher score indicating more disability.
    Time Frame
    Week 4 (Day 29)
    Title
    Change in Quantitative MG (QMG) score from Baseline to Week 4 (Day 29)
    Description
    QMG score is a standardized and validated quantitative strength scoring system that was developed specifically for MG. The QMG total score is obtained by summing the responses to each individual item (13 items; Responses: None=0, Mild=1, Moderate=2, Severe=3). The score ranges from 0 to 39, with lower scores indicating lower disease activity.
    Time Frame
    Week 4 (Day 29)
    Title
    Myasthenia Gravis Foundation of America Post-Interventional Status (MGFA-PIS) at Week 4 (Day 29)
    Description
    The MGFA-PIS is a physician-determined assessment of clinical symptoms of MG after initiation of MG specific therapy. For the purpose of the current study, Minimal Manifestation will be determined at each scheduled time point after treatment initiation (rather than after 1 year). Change in status (improved, unchanged, worse, exacerbation, or died of MG) will also be determined.
    Time Frame
    Week 4 (Day 29)
    Title
    Change in Pediatric Quality of Life Inventory (PedsQoL), Version 4 domain scores from Baseline to Week 4 (Day 29)
    Description
    The PedsQoL generic core scale (Version 4) is a validated instrument that is suitable for use with pediatric populations. PedsQoL generic core scales assess Physical Functioning, Emotional Functioning, Social Functioning, and School Functioning. The scale has 23 items with a score range of 0 to 4. Following transformation, the score range of each domain as well as the total score is 0-100 with higher scores indicating higher HRQoL.
    Time Frame
    Week 4 (Day 29)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    2 Years
    Maximum Age & Unit of Time
    17 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Participant must be 2 to <18 years of age at the time of signing the Informed consent/assent according to local regulation Participant has a diagnosis of generalized myasthenia gravis (gMG) confirmed by a prior positive serologic test result to acetylcholine receptor (AChR) prior to Screening Participant meets the criteria as defined by the Myasthenia Gravis Foundation of America (MGFA) Clinical Classification II to IV at Screening Participants with gMG, including: An MG-activities of daily living (MG-ADL) total score of 6 or more in adolescents from 12 years to <18 years of age at Screening Documented weakness in at least 1 limb, neck, or bulbar muscle in children from 2 years to <12 years of age at Screening Documented vaccination against meningococcal infections within 3 years prior to study start. If not fully vaccinated, participants must receive appropriate prophylactic antibiotic treatment until at least 2 weeks after the initial dose of vaccine(s) Exclusion Criteria: Participant has known positive serology for muscle-specific kinase Participant has any medical or psychiatric condition that, in the opinion of the Investigator, could jeopardize or would compromise the participant's ability to participate in this study Participant has had a thymectomy within 6 months prior to Baseline Participant has minimal Manifestation Status of MG based on the clinical judgement of the Investigator Current or recent systemic infection within 2 weeks prior to Baseline or infection requiring intravenous antibiotics within 4 weeks prior to Baseline
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    UCB Cares
    Phone
    +18445992273 (USA)
    Email
    ucbcares@ucb.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    UCB Cares
    Phone
    001 844 599 2273
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    UCB Cares
    Organizational Affiliation
    001 844 599 2273
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized individual patient-level data and redacted trial documents which may include: analysis-ready datasets, study protocol, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a prespecified time, typically 12 months, on a password protected portal. This plan may change if the risk of re-identifying trial participants is determined to be too high after the trial is completed; in this case and to protect participants, individual patient-level data would not be made available.
    IPD Sharing Time Frame
    Data from this study may be requested by qualified researchers six months after product approval in the US and/or Europe or global development is discontinued, and 18 months after trial completion.
    IPD Sharing Access Criteria
    Qualified researchers may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed.All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal.
    IPD Sharing URL
    http://www.Vivli.org

    Learn more about this trial

    A Study to Evaluate Subcutaneous Zilucoplan in Pediatric Participants With Generalized Myasthenia Gravis

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