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

Study Overview
=================
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).

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

Conditions
-----------------
Generalized Myasthenia Gravis

Intervention / Treatment
-----------------
* Drug: Rozanolixizumab


Participation Criteria
=================
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)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rozanolixizumab dosage regimen 1<br>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<br>* Rozanolixizumab will be administered by subcutaneous infusion in dosage regimen 1 or 2.<br>* Other names: UCB7665;|
| Experimental: Rozanolixizumab dosage regimen 2<br>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<br>* Rozanolixizumab will be administered by subcutaneous infusion in dosage regimen 1 or 2.<br>* 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) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
UCB7665, generalized myasthenia gravis, rozanolixizumab, gMG