A Study to Investigate the Long-term Safety, Tolerability, and Efficacy of Rozanolixizumab in Adult Patients With Generalized Myasthenia Gravis

A Randomized, Open-Label Extension Study to Investigate the Long-Term Safety, Tolerability, and Efficacy of Rozanolixizumab in Adult Patients With Generalized Myasthenia Gravis

The purpose of the MycarinGstudy is to evaluate the long-term safety, tolerability and long-term efficacy of rozanolixizumab in study participants with generalized myasthenia gravis (MG).

Study Overview

• Status: Completed
• Conditions: Generalized Myasthenia Gravis
• Intervention / Treatment: Drug: Rozanolixizumab

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Montréal, Canada
    • Mg0004 50066
  • Québec, Canada
    • Mg0004 50070
  • Toronto, Canada
    • Mg0004 50069
• Czechia
  • Ostrava-Poruba, Czechia
    • Mg0004 40125
  • Praha 2, Czechia
    • Mg0004 40124
• Denmark
  • Aalborg, Denmark
    • Mg0004 40128
• France
  • Bordeaux, France
    • Mg0004 40129
  • Nice, France
    • Mg0004 40132
  • Paris, France
    • Mg0004 40133
  • Strasbourg, France
    • Mg0004 40131
• Germany
  • Göttingen, Germany
    • Mg0004 40140
  • Leipzig, Germany
    • Mg0004 40078
  • Münster, Germany
    • Mg0004 40177
• Italy
  • Milano, Italy
    • Mg0004 40144
  • Pavia, Italy
    • Mg0004 40146
  • Roma, Italy
    • Mg0004 40150
  • Roma, Italy
    • Mg0004 40148
• Japan
  • Hanamaki shi, Japan
    • Mg0004 20078
  • Hiroshima, Japan
    • Mg0004 20079
  • Miyagi, Japan
    • Mg0004 20077
  • Shinjuku-Ku, Japan
    • Mg0004 20076
  • Suita, Japan
    • Mg0004 20032
• Poland
  • Gdańsk, Poland
    • Mg0004 40155
  • Lublin, Poland
    • Mg0004 40151
  • Łódź, Poland
    • Mg0004 40154
• Russian Federation
  • Moscow, Russian Federation
    • Mg0004 20027
  • Saint Petersburg, Russian Federation
    • Mg0004 20001
  • Saint Petersburg, Russian Federation
    • Mg0004 20028
  • Saint Petersburg, Russian Federation
    • Mg0004 20055
• Spain
  • Barcelona, Spain
    • Mg0004 40159
  • Hospitalet de Llobregat, Spain
    • Mg0004 40157
• Taiwan
  • Taichung, Taiwan
    • Mg0004 20080
  • Taipei, Taiwan
    • Mg0004 20081
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013-4409
      • Mg0004 50081
  • California
    • Los Angeles, California, United States, 90033
      • Mg0004 50072
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • Mg0004 50088
  • Florida
    • Miami, Florida, United States, 33144
      • Mg0004 50120
    • Tampa, Florida, United States, 33612
      • Mg0004 50073
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Mg0004 50114
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Mg0004 50121
  • New York
    • New York, New York, United States, 10021
      • Mg0004 50077
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Mg0004 50090
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Mg0004 50096

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant was eligible for MG0003 [NCT03971422] or MGC003 at the time of enrollment into either study and the participant either completed the observation Period of MG0003 or MGC003 or required rescue therapy during the Observation Period of the lead-in studies
• Body weight ≥35 kg at Visit 1
• Study participants may be male or female

Exclusion Criteria:

• Evidence of active or latent tuberculosis (TB) as documented by medical history and examination, if applicable, chest X-rays (posterior anterior and lateral), and TB testing by a positive (not indeterminate) QuantiFERON®-TB Gold Plus
• Participant has received a live vaccination within 8 weeks prior to the Baseline visit; or intends to have a live vaccination during the course of the study or within 8 weeks following the final dose of study medication
• Study participant has experienced hypersensitivity reaction after exposure to other anti-neonatal Fc receptor (FcRn) drugs - Study participant with severe (defined as Grade 3 on the myasthenia gravis-activates of daily living (MG-ADL) scale) weakness affecting oropharyngeal or respiratory muscles, or who has myasthenic crisis or impending crisis
• Participant has any laboratory abnormality that, in the opinion of the Investigator, is clinically significant, has not resolved at randomization, and could jeopardize or compromise the study participant's ability to participate in this study
• Study participant met any mandatory withdrawal or mandatory study drug discontinuation criteria MG0003 [NCT03971422] or MGC003, or discontinued study medication in either study, with the exception of discontinuation due to a need for rescue treatment
• Study participant is not considered capable of adhering to the protocol visit schedule, or medication intake according to the judgment of the Investigator
• Study participant has a lifetime history of suicide attempt (including an active attempt, interrupted attempt, or aborted attempt), or had suicidal ideation since the last visit in MG0003 as indicated by a positive response (Yes) to either Question 4 or Question 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rozanolixizumab dosage regimen 1; Study participants randomized to dosage regimen 1 will receive assigned dosage of rozanolixizumab at pre-specified time points during the Treatment Period. The dose regimen may be switched based on investigator discretion.	Drug: Rozanolixizumab; Rozanolixizumab will be administered by subcutaneous infusion in dosage regimen 1 or 2.; Other Names: UCB7665
Experimental: Rozanolixizumab dosage regimen 2; Study participants randomized to dosage regimen 2 will receive assigned dosage of rozanolixizumab at pre-specified time points during the Treatment Period. The dose regimen may be switched based on investigator discretion.	Drug: Rozanolixizumab; Rozanolixizumab will be administered by subcutaneous infusion in dosage regimen 1 or 2.; Other Names: UCB7665

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)	A TEAE is defined as an AE starting on or after the time of first administration of investigational medicinal product (IMP) or any unresolved event already present before the first administration of IMP that worsened in intensity following exposure to IMP, up to 8 weeks after the last dose of IMP in study participants who discontinued the study or IMP.	From Baseline until End of Study (up to Week 60)
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Permanent Withdrawal of Study Medication	A TEAE is defined as an AE starting on or after the time of first administration of IMP or any unresolved event already present before the first administration of IMP that worsened in intensity following exposure to IMP, up to 8 weeks after the last dose of IMP in study participants who discontinued the study or IMP.	From Baseline until End of Study (up to Week 60)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Total Score at Each Scheduled Assessment During Treatment and Observation Periods	The Myasthenia Gravis Activities of Daily Living (MG-ADL) is an 8-item patient-reported outcome (PRO) instrument developed on the basis of the Quantitative Myasthenia Gravis (QMG). The MG-ADL targeted symptoms and disability across ocular, bulbar, respiratory, and axial symptoms. The total MG-ADL score was obtained by summing the responses to each individual item (8 items; Grades: 0, 1, 2, 3), where 0 represents no symptoms or impaired performance and 3 represents the most severe symptoms or impaired performance. The total score ranges from 0 to 24, with a higher score indicating more disability. A positive change indicates worsening and a negative change indicates improvement.	Baseline, Weeks 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 52 and 60
Change From Baseline in Myasthenia Gravis-Composite (MG-C) Total Score at Each Scheduled Assessment During Treatment and Observation Periods	MG-C scale is a validated assessment and scale tests 10 items with individual items being weighted differently. The items included ptosis/upward gaze (range: 0 [>45 second] - 3 [Immediate]), double vision on lateral gaze (range: 0 [>45 second] - 4 [Immediate]), eye closure (range: 0 [Normal] - 2 [severe weakness]), talking (range: 0 [Normal] - 6 [difficult to understand speech]), chewing (range: 0 [Normal] - 6 [gastric tube]), swallowing (range: 0 [Normal] - 6 [gastric tube]), breathing (range: 0 [Normal] - 9 [ventilator dependence]), neck flexion (range: 0 [Normal] - 4 [severe weakness]), shoulder abduction (range: 0 [Normal] - 5 [severe weakness]) and hip flexion (range: 0 [Normal] - 5 [severe weakness]), lower scores= lower disease activity. Total MG-C score was obtained by summing responses to each individual item and score ranges from 0 to 50, with lower scores indicating lower disease activity. A positive change indicates worsening and a negative change indicates improvement.	Baseline, Weeks 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 52 and 60
Change From Baseline in Quantitative Myasthenia Gravis (QMG) Total Score at Each Scheduled Assessment During Treatment and Observation Periods	The QMG is a validated assessment and the scale tested 13 items, including ocular and facial involvement, swallowing, speech, limb strength, and forced vital capacity. The total QMG score was obtained by summing the responses to each individual item (13 items; Responses: None=0, Mild=1, Moderate=2, Severe=3) and the score ranges from 0 to 39, with lower scores indicating lower disease activity. A positive change indicates worsening and a negative change indicates improvement.	Baseline, Weeks 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 52 and 60
Percentage of Participants Using Rescue Medication (Intravenous Infusion of Immunoglobulin G (IVIg) or Plasma Exchange (PEX))	Rescue therapy consisted of IVIg or PEX. Study participants who experienced disease worsening (eg, an increase of 2 points on the MG-ADL or 3 points on the QMG scale between 2 consecutive visits) may be considered for rescue therapy at the discretion of the Investigator.	From Baseline until End of Study (up to Week 60)

Collaborators and Investigators

• Sponsor: UCB Biopharma SRL
• Investigators: Study Director: UCB Cares, 001 844 599 22733 (UCB)

Study record dates

Study Major Dates

• Study Start (Actual): October 29, 2019
• Primary Completion (Actual): September 1, 2021
• Study Completion (Actual): September 1, 2021

Study Registration Dates

• First Submitted: October 11, 2019
• First Submitted That Met QC Criteria: October 11, 2019
• First Posted (Actual): October 14, 2019

Study Record Updates

• Last Update Posted (Actual): September 5, 2023
• Last Update Submitted That Met QC Criteria: August 22, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: gMG; rozanolixizumab; UCB7665; generalized myasthenia gravis
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Neoplasms; Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Neoplasms by Site; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Neuromuscular Manifestations; Nervous System Neoplasms; Paraneoplastic Syndromes, Nervous System; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Muscle Weakness; Myasthenia Gravis; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Rozanolixizumab
• Other Study ID Numbers: MG0004; 2019-000969-21 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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 Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• 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