A Study to Test Efficacy and Safety of Rozanolixizumab in Adult Patients With Generalized Myasthenia Gravis

• ClinicalTrials.gov Identifier: NCT03971422
• Recruitment Status: Completed
• First Posted: June 3, 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: May 29, 2019
• First Posted Date: June 3, 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: June 3, 2019
• Actual Primary Completion Date: August 31, 2021 (Final data collection date for primary outcome measure)

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

Change From Baseline to Day 43 in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Score [ Time Frame: Baseline and Day 43 ]

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 in the score indicates worsening and a negative change indicates improvement.

Original Primary Outcome Measures (submitted: May 29, 2019)

Change from Baseline to Visit 10 in Myasthenia Gravis-Activities of Daily Living (MG-ADL) score [ Time Frame: Baseline and Visit 10 (Day 43) ]

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.

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

• Percentage of Participants Achieving Myasthenia Gravis-Activities of Daily Living (MG-ADL) Response at Day 43 [ Time Frame: Day 43 ]
  The MG-ADL is an 8-item PRO instrument developed on the basis of the 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 in the score indicates worsening and a negative change indicates improvement. Study participants were classified as responders at Day 43 if the value was at least a 2-point improvement (decrease) from Baseline at Day 43.
• Change From Baseline to Day 43 in Myasthenia Gravis-Composite (MG-C) Total Score [ Time Frame: Baseline and Day 43 ]
  MG-C scale is a validated assessment and scale tests 10 items with individual item 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 to Day 43 in Quantitative Myasthenia Gravis (QMG) Total Score [ Time Frame: Baseline and Day 43 ]
  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 in the score indicates worsening and a negative change indicates improvement.
• Change From Baseline to Day 43 in the Myasthenia Gravis (MG) Symptoms Patient Reported Outcome (PRO) 'Muscle Weakness Fatigability' Score [ Time Frame: Baseline and Day 43 ]
  MG symptoms PRO instrument consisted of 42 items across 5 scales: ocular muscle weakness (items 1-5); bulbar muscle weakness (items 6-15); respiratory muscle weakness (items 16-18); physical fatigue (items 19-33) and muscle weakness fatigability (items 34-42). Study participants were asked to choose response option that how frequently they experienced muscle weakness fatigability (items 34-42) over the past 7 days using a 5-point Likert scale (1="none of the time" to 5="all of the time") for each item. Sum of each item score is linearly transformed to have all domain scores ranging from 0 to 100. Total score is calculated as: (sum of item scores within the scale)/(raw score range) x (total number of items in the scale)/(number of non-missing items in the scale) x100 and ranged from 0 to 100, where higher scores indicated severe symptoms.
• Change From Baseline to Day 43 in the Myasthenia Gravis (MG) Symptoms Patient Reported Outcome (PRO) 'Physical Fatigue' Score [ Time Frame: Baseline and Day 43 ]
  The MG symptoms PRO instrument consisted of 42 items across 5 scales: ocular muscle weakness (items 1-5); bulbar muscle weakness (items 6-15); respiratory muscle weakness (items 16-18); physical fatigue (items 19-33) and muscle weakness fatigability (items 34-42). Study participants were asked to choose the response option that how frequently they experienced physical fatigue (items 19-33) over the past 7 days using a 5-point Likert scale (1="none of the time" to 5="all of the time") for each item. Sum of each item score is linearly transformed to have all domain scores ranging from 0 to 100. Total score is calculated as: (sum of item scores within the scale)/(raw score range) x (total number of items in the scale)/(number of non-missing items in the scale) x100 and ranged from 0 to 100, where higher scores indicated severe symptoms.
• Change From Baseline to Day 43 in the Myasthenia Gravis (MG) Symptoms Patient Reported Outcome (PRO) 'Bulbar Symptoms' Score [ Time Frame: Baseline and Day 43 ]
  The MG symptoms PRO instrument consisted of 42 items across 5 scales: ocular muscle weakness (items 1-5); bulbar muscle weakness (items 6-15); respiratory muscle weakness (items 16-18); physical fatigue (items 19-33) and muscle weakness fatigability (items 34-42). Study participants were asked to choose response option that best described severity of bulbar muscle weakness (items 6-15) symptoms over past 7 days using a 4-point Likert scale (1="none" to 4="severe") for each item. Sum of each item score is linearly transformed to have all domain scores ranging from 0 to 100. Total score is calculated as: (sum of item scores within the scale)/(raw score range) x (total number of items in the scale)/(number of non-missing items in the scale) x100 and ranged from 0 to 100, where higher scores indicated severe symptoms.
• Number of Participants With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: From Baseline until End of Study Visit (up to Week 14) ]
  A TEAE is defined as an AE starting on or after the time of first administration of investigational medicinal product (IMP) up to and including 8 weeks after the last dose.
• Number of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Withdrawal of Investigational Medicinal Product (IMP) [ Time Frame: From Baseline until End of Study Visit (up to Week 14) ]
  A TEAE is defined as an AE starting on or after the time of first administration of IMP up to and including 8 weeks after the last dose.

Original Secondary Outcome Measures (submitted: May 29, 2019)

• Percentage of participants achieving Myasthenia Gravis-Activities of Daily Living (MG-ADL) response at Visit 10 [ Time Frame: Visit 10 (Day 43) ]
• Change from Baseline to Visit 10 in Myasthenia Gravis-Composite score [ Time Frame: Baseline and Visit 10 (Day 43) ]
  The total Myasthenia Gravis(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 to Visit 10 in Quantitative Myasthenia Gravis (QMG) score [ Time Frame: Baseline and Visit 10 (Day 43) ]
  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.
• Change from Baseline to Visit 10 in the Myasthenia Gravis (MG) Symptoms Patient Reported Outcome (PRO) 'Fatigability' score [ Time Frame: Baseline and Visit 10 (Day 43) ]
  The MG symptoms PRO instrument consists of 42 items across 5 scales: ocular symptoms (items 1-5); bulbar symptoms (items 6-15); respiratory symptoms (items 16-18); physical fatigue (items 19-33) and muscle weakness fatigability (items 34-42). The study participant will be asked to choose the response option that best describes the severity of ocular, bulbar, and respiratory symptoms over the past 7 days using a 4-point Likert scale ("none" to "severe") and how frequently they experience physical fatigue and muscle weakness fatigability over the past 7 days using a 5-point Likert scale ("none of the time" to "all of the time"), respectively.
• Change from Baseline to Visit 10 in the Myasthenia Gravis (MG) Symptoms Patient Reported Outcome (PRO) 'Physical Fatigue, Limb and Axial Weakness' score [ Time Frame: Baseline and Visit 10 (Day 43) ]
  The MG symptoms PRO instrument consists of 42 items across 5 scales: ocular symptoms (items 1-5); bulbar symptoms (items 6-15); respiratory symptoms (items 16-18); physical fatigue (items 19-33) and muscle weakness fatigability (items 34-42). The study participant will be asked to choose the response option that best describes the severity of ocular, bulbar, and respiratory symptoms over the past 7 days using a 4-point Likert scale ("none" to "severe") and how frequently they experience physical fatigue and muscle weakness fatigability over the past 7 days using a 5-point Likert scale ("none of the time" to "all of the time"), respectively.
• Change from Baseline to Visit 10 in the Myasthenia Gravis (MG) Symptoms Patient Reported Outcome (PRO) 'Bulbar' score [ Time Frame: Baseline and Visit 10 (Day 43) ]
  The MG symptoms PRO instrument consists of 42 items across 5 scales: ocular symptoms (items 1-5); bulbar symptoms (items 6-15); respiratory symptoms (items 16-18); physical fatigue (items 19-33) and muscle weakness fatigability (items 34-42). The study participant will be asked to choose the response option that best describes the severity of ocular, bulbar, and respiratory symptoms over the past 7 days using a 4-point Likert scale ("none" to "severe") and how frequently they experience physical fatigue and muscle weakness fatigability over the past 7 days using a 5-point Likert scale ("none of the time" to "all of the time"), respectively.
• Occurrence of treatment-emergent adverse events (TEAEs) [ Time Frame: From Baseline until End of Study Visit (up to Week 14) ]
  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. A Treatment emergent adverse event (TEAE) is defined as any event that was not present prior to the first administration of IMP or any unresolved event already present before the first administration of IMP that worsens in intensity following exposure to treatment.
• Treatment-emergent adverse events (TEAEs) leading to withdrawal of investigational medicinal product (IMP) [ Time Frame: From Baseline until End of Study Visit (up to Week 14) ]
  One of the secondary outcome measures is to assess safety and tolerability of the IMP in the MG patients. This can be measured by Treatment emergent adverse events (TEAEs) leading to withdrawal of IMP. A TEAE is defined as any event that was not present prior to the first administration of IMP or any unresolved event already present before the first administration of IMP that worsens in intensity following exposure to treatment.

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

Descriptive Information

• Brief Title: A Study to Test Efficacy and Safety of Rozanolixizumab in Adult Patients With Generalized Myasthenia Gravis
• Official Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating Efficacy and Safety of Rozanolixizumab in Adult Patients With Generalized Myasthenia Gravis
• Brief Summary: The purpose of the MycarinGstudy is to demonstrate the clinical efficacy and to assess safety and tolerability of rozanolixizumab in patients with generalized myasthenia gravis (MG).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); 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
• Other: Placebo
  Subjects will receive placebo at pre-specified time points.
  Other Name: PBO

Study Arms

• Experimental: Dosage Regimen 1
  Study participants randomized to dosage regimen 1 will receive assigned dosage of rozanolixizumab at pre-specified time points during Treatment Period.
  Intervention: Drug: Rozanolixizumab
• Experimental: Dosage Regimen 2
  Study participants randomized to dosage regimen 2 will receive assigned dosage of rozanolixizumab at pre-specified time points during Treatment Period.
  Intervention: Drug: Rozanolixizumab
• Placebo Comparator: Placebo
  Study participants randomized to this arm will receive placebo.
  Intervention: Other: Placebo

Publications *

• Bril V, Druzdz A, Grosskreutz J, Habib AA, Mantegazza R, Sacconi S, Utsugisawa K, Vissing J, Vu T, Boehnlein M, Bozorg A, Gayfieva M, Greve B, Woltering F, Kaminski HJ; MG0003 study team. Safety and efficacy of rozanolixizumab in patients with generalised myasthenia gravis (MycarinG): a randomised, double-blind, placebo-controlled, adaptive phase 3 study. Lancet Neurol. 2023 May;22(5):383-394. doi: 10.1016/S1474-4422(23)00077-7. Erratum In: Lancet Neurol. 2023 Oct;22(10):e11.
• Bril V, Benatar M, Andersen H, Vissing J, Brock M, Greve B, Kiessling P, Woltering F, Griffin L, Van den Bergh P; MG0002 Investigators. Efficacy and Safety of Rozanolixizumab in Moderate to Severe Generalized Myasthenia Gravis: A Phase 2 Randomized Control Trial. Neurology. 2021 Feb 9;96(6):e853-e865. doi: 10.1212/WNL.0000000000011108. Epub 2020 Nov 20.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 30, 2021): 200
• Original Estimated Enrollment (submitted: May 29, 2019): 240
• Actual Study Completion Date: October 26, 2021
• Actual Primary Completion Date: August 31, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Study participant must be ≥18 years of age, at the time of signing the informed consent
• Study participant has documented diagnosis of generalized myasthenia gravis (gMG) at Visit 1, based on study participant's history and supported by previous evaluations
• Study participant has a confirmed positive record of autoantibodies against acetylcholine receptor (AChR) or muscle-specific kinase (MuSK) at Screening (Visit 1).The presence of autoantibodies may be confirmed with repeat testing at Visit 1
• Study participant has Myasthenia Gravis Foundation of America (MGFA) Class II to IVa at Visit 1
• Study participant with a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of at least 3 (with ≥3 points from non-ocular symptom) AND a quantitative myasthenia gravis (QMG) score of at least 11 at Visit 1 and at Baseline (Visit 2)
• Study participant is considered for additional treatment such as intravenous immunoglobulin g (IVIg) or plasma exchange (PEX) by the Investigator

Exclusion Criteria:

• Study participant has a known history of hyperprolinemia
• Study participant has a clinically relevant active infection (eg, sepsis, pneumonia, or abscess) in the opinion of the Investigator, or had a serious infection (resulting in hospitalization or requiring parenteral antibiotic treatment) within 6 weeks prior to the first dose of investigational medicinal product (IMP)
• Study participant with a known tuberculosis (TB) infection, at high risk of acquiring TB infection, or latent tuberculosis infection (LTBI), or current/history of nontuberculous mycobacterial infection (NTMBI) will be excluded
• 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-Activities of Daily Living (MG-ADL) scale) weakness affecting oropharyngeal or respiratory muscles, or who has myasthenic crisis or impending crisis at Visit 1 or Visit 2
• Study participant has a history of a solid organ transplant or hematopoietic stem cell/marrow transplant

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: Belgium, Canada, Czechia, Denmark, France, Georgia, Germany, Hungary, Italy, Japan, Poland, Russian Federation, Serbia, Spain, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT03971422
• Other Study ID Numbers: MG0003; 2019-000968-18 ( 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: https://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; +1 844 599 2273 (UCB)

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