generalized myasthenia gravis

Primary:  To demonstrate the clinical efficacy of rozanolixizumab in patients with generalized MG Secondary:  To assess safety and tolerability of rozanolixizumab in MG patients

Rozanolixizumab

Rozanolixizumab

vial

140

Primary end point(s): Change from Baseline to Day 43 (Visit 10) in Myasthenia Gravis-Activities of Daily Living (MG-ADL) score

Secondary end point(s):
1. Percentage of participants achieving Myasthenia Gravis-Activities of Daily Living (MG-ADL) response at Visit 10
2. Change from Baseline to (Day 43) Visit 10 in the Myasthenia Gravis- Composite score (MG-C)
3. Change from Baseline to (Day 43) Visit 10 in Quantitative Myasthenia Gravis (QMG) score
4. Change from Baseline to Visit 10 in the Myasthenia Gravis (MG) Symptoms Patient Reported Outcome (PRO) ′Muscle Weakness Fatigability′ score
5. Change from Baseline to (Day 43) Visit 10 in the Myasthenia Gravis (MG) Symptoms Patient Reported Outcome (PRO) ′Physical Fatigue′ score
6. Change from Baseline to Visit 10 in the Myasthenia Gravis (MG) Symptoms Patient Reported Outcome (PRO) ′Bulbar Symptoms′ score
7. Occurrence of treatment-emergent adverse events (TEAEs)
8. Treatment-emergent adverse events (TEAEs) leading to withdrawal of investigational medicinal product (IMP)

Age
1. Study participant must be ≥18 years of age, at the time of signing the informed consent.
Type of participant and disease characteristics
2. Study participant has documented diagnosis of gMG at Visit 1, based on study participant’s
history and supported by previous evaluations.
3. Study participant has a confirmed positive record of autoantibodies against AChR or MuSK
prior to Visit 1.
4. Study participant has MGFA Class II to IVa at Visit 1.
5. Study participant with a MG-ADL score of at least 3 AND a QMG score of at least 11 at
Visit 1 and at Baseline (Visit 2).
6. Study participant is considered for treatment with IVIg or PEX by the Investigator.
Weight
7. Body weight >35kg at Visit 1.
Sex
8. Study participants may be male or female
 A male study participant must agree to use contraception as detailed in Appendix 4
(Section 10.4) of this protocol during the Treatment Period and for at least 90 days after
the last dose of study treatment and refrain from donating sperm during this period.
 Female study participants of childbearing potential must agree to use a highly effective
method of birth control, during the study and for a period of 90 days after their final dose
of study medication. According to the ICHM3 (R2), highly effective forms of birth
control are methods that achieve a failure rate of less than 1% per year when used
consistently and correctly.
 A female participant is eligible to participate if she is not pregnant (see Section 10.4), not
breastfeeding, and at least one of the following conditions applies:
◦ Not a woman of childbearing potential (WOCBP) as defined in Section 10.4
OR
◦ A WOCBP who agrees to follow the contraceptive guidance in Section 10.4 during
the Treatment Period and for at least 90 days after the last dose of study treatment.
The study participant must have a negative serum pregnancy test at the Screening
Visit, which is confirmed to be negative by urine testing prior to the first dose of
study medication at Visit 2 and prior to further dosing at each study visit thereafter.
Informed consent
9. Capable of giving signed informed consent as described in Appendix 1, Section 10.1.3
which includes compliance with the requirements and restrictions listed in the informed
consent form (ICF) and in this protocol.

Medical conditions
1. Study participant has any medical or psychiatric condition that, in the opinion of the
Investigator, could jeopardize or would compromise the study participant’s ability to
participate in this study.
2. Study participant has a history of alcohol or drug abuse within the previous 12 months.
3. Study participant has a known hypersensitivity to any components of the study medication or
comparative drugs as stated in this protocol.
4. Study participant has a history of hyperprolinemia, since L-proline is a constituent of the
rozanolixizumab formulation.
5. 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 IMP.
6. 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.
Prior/Concomitant therapy
7. Study participant has previously received rozanolixizumab drug product.
8. Study 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 IMP.
9. Study participant has been treated with prohibited immunosuppressants, biologics, and other
therapies within timeframe shorter than no-treatment period detailed in Table 5-1.
10. Study Participant has been treated with any biological agent other than those listed in
Table 5-1 in the past 3 months or within 5 half-lives prior to Baseline, whichever was longer.
11. Study participant has prior treatment with rituximab in the 6 months prior to the Baseline
Visit or study participant has prior treatment with rituximab in the 12 months prior to the
Baseline Visit and B cells monitoring have shown they did not return to normal range.
12. Study participant had a thymectomy in the past 6 months or a thymoma at any time that
required chemotherapy and/or radiotherapy.
13. Study participant has active inflammatory bowel disease (IBD) or GI ulceration or history
thereof in past 6 months.
Prior/Concurrent clinical study experience
14. Study participant has participated in another study of an IMP (and/or an investigational
device) within the previous 3 months or is currently participating in another study of an IMP
and/or an investigational device.
15. Study participant has previously participated in the Phase 2 study, MG0002.
16. Study participant has experienced hypersensitivity reaction after exposure to other anti-FcRn
drugs.
Diagnostic assessments
17. Study participant with severe (defined as Grade 3 on the MG-ADL scale) weakness affecting
oropharyngeal or respiratory muscles, or who has myasthenic crisis or impending crisis a
Visit 1 .
18. Study participant has a serum total IgG level ≤5.5g/L at Visit 1.
19. Study participant has absolute neutrophil count <1500 cells/mm3.
20. Study 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.
21. Study participant has 12-lead ECG with findings considered to be clinically significant upon
medical review. The clinical significance of the findings needs to be assessed by the
Investigator to determine eligibility, and any queries regarding continuation of the study
participants will have to be addressed with the Medical Monitor.
22. Study participant has renal impairment, defined as serum creatinine level of ≥1.4mg/dL for
females and ≥1.5mg/dL for males at Visit 1.
23. Alanine transaminase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase
(ALP) are >2x upper limit of normal (ULN), or bilirubin >1.5xULN (isolated bilirubin
>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
Study participant has elevations only in total bilirubin that were >ULN and <1.5xULN,
fractionate bilirubin to identify possible undiagnosed Gilbert's syndrome (ie, direct bilirubin
<35%).
For randomized study participants with a Baseline result >ULN for ALT, AST, ALP, or total
bilirubin but <1.5xULN, a Baseline diagnosis and/or the cause of any clinically meaningful
elevation will have to be understood and recorded in the eCRF.
If study participant has >ULN, ALT, AST, or ALP that does not meet the exclusion limit at
Screening, the tests should be repeated, if possible, prior to dosing to ensure there was no
further ongoing clinically relevant increase. In case of a clinically relevant increase, inclusion
of the study participants will have to be discussed with the Medical Monitor.
Tests that result in ALT, AST, or ALP up to 25% above the exclusion limit (>2xULN) will
have to be repeated once for confirmation. This includes rescreening.
24. Presence of Hepatitis B surface antigen (HBsAg) at Screening
25. Positive Hepatitis C antibody test result at Screening or within 3 months prior to starting
study treatment. NOTE: Study participant with a positive Hepatitis C antibody due to prior
resolved disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is
obtained.
26. Positive Hepatitis C RNA test result at Screening or within 3 months prior to first dose of
study treatment. NOTE: Test is optional and a study participant with negative Hepatitis C
antibody test is not required to also undergo Hepatitis C RNA testing.
27. Current unstable liver or biliary disease per Investigator assessment defined by the presence
of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices,
persistent jaundice, or cirrhosis. NOTE: with exception of stable chronic liver disease
(including Gilbert’s syndrome, asymptomatic gallstones) .
28. Study participant tests positive for HIV at Visit 1.
29. Study participant has a family history (immediate family member) of primary
immunodeficiency.
30. Study participant has active neoplastic disease or history of neoplastic disease within 5 years
of study entry (except for basal or squamous cell carcinoma of the skin or carcinoma in situ
of the uterine cervix that have been definitively treated with standard of care approaches).
31. Study participant has a planned elective surgical procedure within 4 months.
32. Study participant has a history of a solid organ transplant or hematopoietic stem cell/marrow
transplant.
33. Study participant has corrected QT interval (QTc) >450 msec (for male participants) or
QTc >470 msec (for female participants) or QTc >480 msec in participants with bundle
branch block.
Other exclusions
34. The study participant is not considered capable of adhering to the protocol visit schedule, or
medication intake according to the judgment of the Investigator.
35. A female study participant, who tests positive for pregnancy, plans to get pregnant during the
participation in the study, or who is breastfeeding.
36. Study participant has a lifetime history of suicide attempt (including an active attempt,
interrupted attempt, or aborted attempt), or had suicidal ideation in the past 6 months as
indicated by a positive response (Yes) to either Question 4 or Question 5 of the Columbia
Suicide Severity Rating Scale (C-SSRS) at Visit 1.
37. Any recreational or medicinal use of cannabis (ie, marijuana) or cannabidiols.