Clinical Trials List
Protocol NumberMG0004
2020-05-01 - 2021-12-27
Phase III
Not yet recruiting2
Recruiting1
Study ended1
ICD-10G70.00
Myasthenia gravis without (acute) exacerbation
ICD-10G70.01
Myasthenia gravis with (acute) exacerbation
ICD-9358.0
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
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Trial Applicant
PAREXEL INTERNATIONAL CO., LTD.
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Sponsor
-
Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Hou-Chang Chiu Division of Neurology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 張國軒 Division of Neurology
- 呂榮國 Division of Neurology
- Chin-Chang Huang Division of Neurology
- 朱俊哲 Division of Neurology
- Hong-Chou Kuo Division of Neurology
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- Yi-Chu Liao Division of Neurology
- 賴冠霖 Division of Neurology
- Kon-Ping Lin Division of Neurology
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- Ching-Hua Lu Lu Division of Neurology
The Actual Total Number of Participants Enrolled
0 Study ended
Condition/Disease
myasthenia gravis
Objectives
To evaluate the long-term safety and tolerability of rozanolixizumab in study participants with generalized MG
To assess the reduction in use of steroids in study participants receiving rozanolixizumab
To assess the plasma concentrations of rozanolixizumab administered by SC infusion
To assess the pharmacodynamic effects of rozanolixizumab as measured by IgG levels IgG
subclasses, MG-specific autoantibodies levels, and NF-L levels
To evaluate the incidence and emergence of ADAs with respect to immunogenicity, PK, and
pharmacodynamics
To assess the effect of rozanolixizumab on biomarkers including albumin, α- and β-globulins, IgG subclasses, IgM, IgA, and IgE, serum and plasma complement levels, and serum cytokines
To assess the effect of rozanolixizumab on tetanus IgG antibodies
To evaluate the effects of rozanolixizumab on exploratory biomarkers and explore the
relationship between exploratory biomarkers andcause, progression, and appropriate treatment of MG
Test Drug
Rozanolixizumab
Active Ingredient
Rozanolixizumab
Dosage Form
Injection
Dosage
140
Endpoints
To evaluate the long-term safety and tolerability of rozanolixizumab in study participants with generalized MG
To assess the reduction in use of steroids in study participants receiving rozanolixizumab
To assess the plasma concentrations of rozanolixizumab administered by SC infusion
To assess the pharmacodynamic effects of rozanolixizumab as measured by IgG levels IgG
subclasses, MG-specific autoantibodies levels, and NF-L levels
To evaluate the incidence and emergence of ADAs with respect to immunogenicity, PK, and
pharmacodynamics
To assess the effect of rozanolixizumab on biomarkers including albumin, α- and β-globulins, IgG subclasses, IgM, IgA, and IgE, serum and plasma complement levels, and serum cytokines
To assess the effect of rozanolixizumab on tetanus IgG antibodies
To assess the reduction in use of steroids in study participants receiving rozanolixizumab
To assess the plasma concentrations of rozanolixizumab administered by SC infusion
To assess the pharmacodynamic effects of rozanolixizumab as measured by IgG levels IgG
subclasses, MG-specific autoantibodies levels, and NF-L levels
To evaluate the incidence and emergence of ADAs with respect to immunogenicity, PK, and
pharmacodynamics
To assess the effect of rozanolixizumab on biomarkers including albumin, α- and β-globulins, IgG subclasses, IgM, IgA, and IgE, serum and plasma complement levels, and serum cytokines
To assess the effect of rozanolixizumab on tetanus IgG antibodies
Inclution Criteria
1. Participant must be ≥18 years of age at the time of signing the informed consent.
Type of participant and disease characteristics 2a. Participant was eligible for MG0003 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.
Weight
3a. Body weight ≥35kg at Visit 1.
Sex
4. Participants may be male or female.
A male 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 International Council for Harmonisation (ICH) M3 (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 Appendix 4,
Section 10.4), not breastfeeding, and at least one of the following conditions applies:
o Not a woman of childbearing potential (WOCBP) as defined in Appendix 4 (Section 10.4)
OR
o A WOCBP who agrees to follow the contraceptive guidance in Appendix 4 (Section 10.4) during the Treatment Period and for at least 90 days after the last dose of study treatment.
Informed consent
5. Capable of giving signed informed consent as described in Appendix 1 (Section 10.1) which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Type of participant and disease characteristics 2a. Participant was eligible for MG0003 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.
Weight
3a. Body weight ≥35kg at Visit 1.
Sex
4. Participants may be male or female.
A male 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 International Council for Harmonisation (ICH) M3 (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 Appendix 4,
Section 10.4), not breastfeeding, and at least one of the following conditions applies:
o Not a woman of childbearing potential (WOCBP) as defined in Appendix 4 (Section 10.4)
OR
o A WOCBP who agrees to follow the contraceptive guidance in Appendix 4 (Section 10.4) during the Treatment Period and for at least 90 days after the last dose of study treatment.
Informed consent
5. Capable of giving signed informed consent as described in Appendix 1 (Section 10.1) which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Exclusion Criteria
For criteria pertaining to laboratory measures, the last value from MG0003 or MGC003 will be used for evaluation of study participant eligibility, as long as the measurement was taken within the last 4 weeks prior to MG0004 screening.
Unless otherwise stated, each criterion is applicable to the Screening visit (Visit 1). Participants are excluded from the study if any of the following criteria apply:
Medical conditions
1. 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.
2a. Participant has a history of use disorder or other substance use disorder (as per Diagnostic and Statistical Manual of Mental Disorders-5) within the previous 12 months.
3. Participant has a known hypersensitivity to any components of the study medication.
4a. 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.
Prior/Concomitant therapy
5. 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.
Prior/Concurrent clinical study experience
6. Study participant has experienced hypersensitivity reaction after exposure to other anti-FcRn drugs.
Diagnostic assessments
7. 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.
8. Participant has absolute neutrophil count <1500 cells/mm3.
9. 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.
10. Participant has 12-lead electrocardiogram (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 participant must be addressed with the Medical Monitor.
11a.Study participant has renal impairment, defined as GFR less than 60ml/min/1.73m2.
12a.Study participant has >3x upper limit of normal (ULN) of any of the following at Visit 1:
alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase
(ALP), or bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is
fractionated and direct bilirubin <35%).
If study participant has elevations only in total bilirubin that are >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 must be understood and recorded in the electronic Case Report form (eCRF).
Tests that result in ALT, AST, or ALP up to 25% above the exclusion limit (>3xULN) may
be repeated once for confirmation.
13. Study participant has positive human immunodeficiency virus antibody test.
Other exclusions
14a.Study participant met any mandatory withdrawal or mandatory study drug discontinuation criteria MG0003 or MGC003, or discontinued study medication in either study, with the exception of discontinuation due to a need for rescue treatment
15. Study participant is not considered capable of adhering to the protocol visit schedule, or medication intake according to the judgment of the Investigator.
16. 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).
Unless otherwise stated, each criterion is applicable to the Screening visit (Visit 1). Participants are excluded from the study if any of the following criteria apply:
Medical conditions
1. 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.
2a. Participant has a history of use disorder or other substance use disorder (as per Diagnostic and Statistical Manual of Mental Disorders-5) within the previous 12 months.
3. Participant has a known hypersensitivity to any components of the study medication.
4a. 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.
Prior/Concomitant therapy
5. 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.
Prior/Concurrent clinical study experience
6. Study participant has experienced hypersensitivity reaction after exposure to other anti-FcRn drugs.
Diagnostic assessments
7. 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.
8. Participant has absolute neutrophil count <1500 cells/mm3.
9. 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.
10. Participant has 12-lead electrocardiogram (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 participant must be addressed with the Medical Monitor.
11a.Study participant has renal impairment, defined as GFR less than 60ml/min/1.73m2.
12a.Study participant has >3x upper limit of normal (ULN) of any of the following at Visit 1:
alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase
(ALP), or bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is
fractionated and direct bilirubin <35%).
If study participant has elevations only in total bilirubin that are >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 must be understood and recorded in the electronic Case Report form (eCRF).
Tests that result in ALT, AST, or ALP up to 25% above the exclusion limit (>3xULN) may
be repeated once for confirmation.
13. Study participant has positive human immunodeficiency virus antibody test.
Other exclusions
14a.Study participant met any mandatory withdrawal or mandatory study drug discontinuation criteria MG0003 or MGC003, or discontinued study medication in either study, with the exception of discontinuation due to a need for rescue treatment
15. Study participant is not considered capable of adhering to the protocol visit schedule, or medication intake according to the judgment of the Investigator.
16. 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).
The Estimated Number of Participants
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Taiwan
10 participants
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Global
276 participants
