全身型重症肌無力

MG0006 將於rozanolixizumab 臨床研發計畫中進行，對象為患有全身型重症肌無力(gMG)的兒童族群。MG0006 的目的為在年齡≥ 2至< 18 歲的兒童試驗參與者中，評估rozanolixizumab 以皮下(sc)方式投予的安全性與耐受性、藥物動力學(PK)與藥物效力學(PD) (免疫球蛋白[Ig]G 的下降)以及活性，該兒童試驗參與者需有gMG 診斷紀錄、有抗乙醯膽鹼受體(AChR)或抗肌肉特異性激酶(MuSK)自體抗體的病史紀錄，並出現不佳臨床反應或gMG 症狀惡化且需要額外治療(例如：靜脈注射免疫球蛋白[IVIg]或血漿置換術[PEX])。 MG0006 在成功完成第3 期樞紐性試驗MG0003 (對象為患有gMG 的成人試驗參與者)後進行。 Rozanolixizumab 在第2 期試驗(MG0002)以及第3 期試驗(MG0003 以及開放性延伸[OLE]試驗MG0004 和MG0007)中已證實能夠顯著降低gMG 成人試驗參與者的血清IgG 與IgG自體抗體濃度，並改善關鍵重症肌無力(MG)臨床結果指標。 主要目的 •評估rozanolixizumab以sc 給藥，用於年齡≥ 2至< 18 歲gMG兒童參與者的安全性與耐受性 次要目標 •評估rozanolixizumab的活性 •評估rozanolixizumab以sc 給藥，用於年齡≥ 2至< 18 歲gMG兒童參與者的安全性與耐受性 •評估rozanolixizumab的藥物動力學(PK) •評估rozanolixizumab的免疫原性 其他目標 •評估rozanolixizumab對IgM 與IgA 濃度的影響評估rozanolixizumab抗藥抗體(ADA)的發生率與出現情況 •評估rozanolixizumab以sc 給藥，用於年齡≥ 2至< 18 歲gMG兒童參與者的安全性與耐受性 •評估rozanolixizumab的活性

注射劑

solution for injection

270

140mg/mL

治療：Rozanolixizumab
目標族群：年齡≥ 2至＜ 18 歲出現中度至重度症狀(依試驗主持人判定)的gMG 孩童及青少年
試驗指標：主要試驗指標之定義如下
併發事件處理：
○ 投予救援療法或變更標準照護(SOC)劑量療程。於併發事件發生當下及之後收集的資料，將用於敘述性統計。將採用「治療方針」法。
○ 參與者停用試驗藥品(IMP)，但繼續參與試驗。於併發事件發生當下及之後收集的資料，將用於敘述性統計。將採用「治療方針」法。
○ 參與者中止試驗參與(退出)。截至併發事件發生當下的資料將用於敘述性統計。將採用「治療方針」法。
族群層級摘要：敘述性統計主要安全性試驗指標(收集至試驗結束[EOS]回診為止)為：
治療中產生的嚴重不良事件(TEAE)發生率
因TEAE 而造成永久停用IMP 的發生率
特別關注之不良事件發生率(AESM)

Study participants are eligible to be included in the study only if all of the following criteria apply:
Age
1. Study participant must be ≥2 to ＜18 years of age inclusive, at the time of signing the informed consent/assent according to local regulation.

Type of participant and disease characteristics
2. Study participant must have a documented diagnosis of gMG at Screening that includes a record confirming the presence of MG specific autoantibodies to AChR or MuSK prior to Screening.
3. Study participant has MGFA Clinical Classification II to IVa at Screening.
4. Study participant has received existing conventional treatment(s) for gMG (eg, pyridostigmine, corticosteroids, and/or immune suppressants) prior to Screening.
5. Study participant has had an unsatisfactory clinical response or worsening of gMG symptoms and is in need of additional therapy (for example, PEX or treatment with IVIg).

Weight
6a. Study participant must be a minimum of 10kg in body weight at Screening and, based on the Investigator's discretion, the participant must be suitable for a sc infusion/injection.
Sex
7. For female study participants:
− A female participant who is sexually active 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:
◦ Not a woman of childbearing potential (WOCBP) as defined in Appendix 4 (Section 10.4)
OR
A WOCBP who agrees to follow the contraceptive guidance or local regulations for the duration of the study and for at least 90 days after the last dose of study treatment. The study participant must have a negative serum pregnancy test at Screening, which is confirmed to be negative by urine testing prior to the first dose of IMP at Baseline.
− A female participant is eligible to participate if she is not a WOCBP and/or not sexually active

Informed consent
8. Study participant is capable of giving/having parent/legal representative(s) provide signedinformed consent/study participant assent (where appropriate) 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/or assent and in the protocol.

Study participants are excluded from the study if any of the following criteria apply:
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 toparticipate in this study.
2. Study participant has a current history of alcohol or drug use disorder, as defined in the Diagnostic and Statistical Manual of Mental Disorders - 5, within the previous 12 months.
3. Study participant has a known hypersensitivity to any components of the IMP or otheranti-FcRn medications.
4. Study participant with severe weakness affecting oropharyngeal or respiratory muscles, or who has myasthenic crisis or impending crisis at Screening or Baseline.
5. Study participant with any active or untreated thymoma. Study participant has a history of thymic carcinoma or thymic malignancy unless it has been deemed cured by adequate treatment with no evidence of recurrence for ≥5 years before Screening.
6. 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.
7. 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).
8. Study participant has a history of, or suspected, lymphoproliferative disease or history of, or suspected, malignancy of any organ system within the past 5 years of study entry prior to Screening.
9. Study participant has a current or medical history of primary immunodeficiency.
10. Study participant with current or medical history of IgA deficiency.
11. Study participant has a history of hyperprolinaemia, since L-proline is a constituent of the IMP.

Prior/Concomitant therapy
12. Study participant has received a live vaccination within 4 weeks prior to Baseline or intends to have a live vaccination during the course of the study.
13. Study participant has had previous therapy with rozanolixizumab or other anti-FcRn drugs.
14. Study participant has a history of thymectomy within 6 months prior to Screening.
15. Study participant has been treated with prohibited immunosuppressants, biologics, and other therapies within a timeframe shorter than the treatment-free period detailed in Table 5-1.

Prior/Concurrent clinical study experience
16. Study participant has participated in another study of an IMP or use of any experimental therapy (and/or an investigational device) within the previous 30 days before the initiation of the IMP on Day 1 in this study, or within 5 half-lives of that investigational product (whichever is greater), or is currently participating in another study of an IMP (and/or an investigational device).

Diagnostic assessments
17. Study participant has a serum total IgG level ≤5.5g/L at Screening.
18. Study participant has an absolute neutrophil count ＜1500cells/mm3 at Screening.
19. Study participant has any laboratory abnormality that, in the opinion of the Investigator, is clinically significant, has not resolved at Baseline, and could jeopardize or compromise the study participant’s ability to participate in this study.
20. Study 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 participants will have to be addressed with the Medical Monitor.
21. Study participant has a current or recent history of clinically significant, severe, and/or
progressive renal disease.
22a. Study participant has renal impairment defined as eGFR ＜45mL/min/1.73 m2 as calculated using the under 25 creatinine-based Chronic Kidney Disease in Children equation (Pierce et al, 2021).
23 Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) are ＞3x upper limit of normal (ULN) defined as per relevant age range at Screening.
24a. Study participant has elevations only in total bilirubin that are ＞1.5xULN (isolated bilirubin ＞1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin is ＜35%) defined as per relevant age range at Screening. For randomized study participants with a Baseline result ＞ULN for ALT, AST, ALP, or total bilirubin, a Baseline diagnosis and/or the cause of any clinically meaningful elevation must be understood and recorded in the electronic case report form (eCRF).
If a study participant has ＞ULN for ALT, AST, or ALP that does not meet the exclusion limit at Screening, repeat the tests, if possible, prior to dosing to ensure there is no further ongoing clinically relevant increase. In case of a clinically relevant increase, inclusion of the study participant must be discussed with the Medical Monitor.
25. Presence of Hepatitis B surface antigen at Screening.
26. Positive Hepatitis C antibody test result at Screening or within 3 months prior to starting IMP. NOTE: Study participant with a positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C ribonucleic acid (RNA) test is obtained.
27. Positive Hepatitis C RNA test result at Screening or within 3 months prior to first dose of IMP. NOTE: Test is optional and a study participant with negative Hepatitis C antibody test is not required to also undergo Hepatitis C RNA testig.
28. Study participant tests positive for human immunodeficiency virus (HIV).
29. Study participant has positive TB test at Screening.
30. Study participant has a planned elective surgical procedure within 4 months after Screening.
31. Study participant has a history of a solid organ transplant or hematopoietic stem cell/marrowtransplant.

Other exclusions
32. A female study participant, who plans to get pregnant during the participation in the study.
33. Study participant has a history of suicide attempt (including an active attempt, interrupted attempt, or aborted attempt), as indicated by a positive response (Yes) to either Question 4 or Question 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) (for study participants aged ≥12 years) or upon medical history (for study participant ＜12 years).