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

• ClinicalTrials.gov Identifier: NCT04124965
• Recruitment Status: Completed
• First Posted: October 14, 2019
• Results First Posted: August 21, 2023
• Last Update Posted: September 5, 2023
• Sponsor: UCB Biopharma SRL
• Information provided by (Responsible Party): UCB Pharma ( UCB Biopharma SRL )

Tracking Information

• First Submitted Date: October 11, 2019
• First Posted Date: October 14, 2019
• Results First Submitted Date: July 27, 2023
• Results First Posted Date: August 21, 2023
• Last Update Posted Date: September 5, 2023
• Actual Study Start Date: October 29, 2019
• Actual Primary Completion Date: September 1, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 27, 2023)

• Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: From Baseline until End of Study (up to Week 60) ]
  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.
• Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Permanent Withdrawal of Study Medication [ Time Frame: From Baseline until End of Study (up to Week 60) ]
  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.

Original Primary Outcome Measures (submitted: October 11, 2019)

• Percentage of participants with treatment-emergent adverse events (TEAEs) [ Time Frame: From Baseline until Final Visit (up to Week 60) ]
  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.
• Percentage of participants with treatment-emergent adverse events (TEAEs) leading to permanent withdrawal of study medication [ Time Frame: From Baseline until Final Visit (up to Week 60) ]
  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.

Current Secondary Outcome Measures (submitted: July 27, 2023)

• Change From Baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Total Score at Each Scheduled Assessment During Treatment and Observation Periods [ Time Frame: Baseline, Weeks 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 52 and 60 ]
  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.
• Change From Baseline in Myasthenia Gravis-Composite (MG-C) Total Score at Each Scheduled Assessment During Treatment and Observation Periods [ Time Frame: Baseline, Weeks 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 52 and 60 ]
  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.
• Change From Baseline in Quantitative Myasthenia Gravis (QMG) Total Score at Each Scheduled Assessment During Treatment and Observation Periods [ Time Frame: Baseline, Weeks 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 52 and 60 ]
  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.
• Percentage of Participants Using Rescue Medication (Intravenous Infusion of Immunoglobulin G (IVIg) or Plasma Exchange (PEX)) [ Time Frame: From Baseline until End of Study (up to Week 60) ]
  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.

Original Secondary Outcome Measures (submitted: October 11, 2019)

• Change from Baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) score at each scheduled assessment during Treatment and Observation Periods [ Time Frame: From Baseline at each scheduled assessment during Treatment and Observation Periods (up to Week 60) ]
  The total MG-ADL score is obtained by summing the responses to each individual item (8 items; Grades: 0, 1, 2, 3). The score ranges from 0 to 24, with a higher score indicating more disability. A positive change indicates worsening and a negative change indicates improvement!
• Change from Baseline in Myasthenia Gravis (MG)-Composite score at each scheduled assessment during Treatment and Observation Periods [ Time Frame: From Baseline at each scheduled assessment during Treatment and Observation Periods (up to Week 60) ]
  The total MG-Composite score is obtained by summing the responses to each individual item (10 items; Grade:0-9 depending on item). The score ranges from 0 to 50, with lower scores indicating lower disease activity.
• Change from Baseline in Quantitative Myasthenia Gravis (QMG) score at each scheduled assessment during Treatment and Observation Periods [ Time Frame: From Baseline at each scheduled assessment during Treatment and Observation Periods (up to Week 60) ]
  The total QMG 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.
• Percentage of participants using rescue medication (intravenous infusion of immunoglobulin G (IVIg) or plasma exchange (PEX)) during the study [ Time Frame: From Baseline at each scheduled assessment during Treatment and Observation Periods (up to Week 60) ]
  Rescue therapy for the study will consist of IVIg or PEX. Study participants who experience 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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Investigate the Long-term Safety, Tolerability, and Efficacy of Rozanolixizumab in Adult Patients With Generalized Myasthenia Gravis
• Official Title: A Randomized, Open-Label Extension Study to Investigate the Long-Term Safety, Tolerability, and Efficacy of Rozanolixizumab in Adult Patients With Generalized Myasthenia Gravis
• Brief Summary: 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Generalized Myasthenia Gravis

Intervention

Drug: Rozanolixizumab

Rozanolixizumab will be administered by subcutaneous infusion in dosage regimen 1 or 2.

Other Name: UCB7665

Study Arms

• 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.
  Intervention: Drug: Rozanolixizumab
• 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.
  Intervention: Drug: Rozanolixizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 23, 2021): 71
• Original Estimated Enrollment (submitted: October 11, 2019): 240
• Actual Study Completion Date: September 1, 2021
• Actual Primary Completion Date: September 1, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Czechia, Denmark, France, Germany, Italy, Japan, Poland, Russian Federation, Spain, Taiwan, United States

Administrative Information

• NCT Number: NCT04124965
• Other Study ID Numbers: MG0004; 2019-000969-21 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• 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.
• 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.
• URL: http://www.Vivli.org

• Current Responsible Party: UCB Pharma ( UCB Biopharma SRL )
• Original Responsible Party: UCB Biopharma S.P.R.L.
• Current Study Sponsor: UCB Biopharma SRL
• Original Study Sponsor: UCB Biopharma S.P.R.L.
• Collaborators: Not Provided

Investigators

• Study Director: UCB Cares; 001 844 599 22733 (UCB)

• PRS Account: UCB Pharma
• Verification Date: August 2023