2025-525127-27-00招募中2 期
A Double-Blind, Randomized, Placebo-Controlled Study to Investigate the Safety and Efficacy of Aritinercept, a Dual BAFF/APRIL Inhibitor, in Patients with Generalized Myasthenia Gravis
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 28
- 试验地点
- 12
- 主要终点
- Phase 1: Incidence of treatment-emergent adverse events; Phase 2: Change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) total score
研究概览
简要总结
Phase 1: To assess the safety and tolerability of aritinercept Phase 2: To assess the efficacy of aritinercept
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Able and willing to sign ICF after receiving information about the Study
- •Male or female patients, 18-70 years of age on the day ICF is signed
- •Body mass index (BMI) 18.0-36.0 kg/m2 and body weight >45 kg
- •Myasthenia Gravis Foundation of America (MGFA) Class II-IV gMG as confirmed by any 1 of the following: • History of abnormal neuromuscular transmission demonstrated by single-fiber electromyography or repetitive nerve stimulation; • History of positive edrophonium chloride test; • Improvement in MG signs on oral acetylcholinesterase inhibitors as assessed by the treating physician
- •Documented history for anti-AChR, anti-MuSK or anti-LRP4 antibodies
- •A total Myasthenia Gravis Activities of Daily Living (MG-ADL) total score of ≥6 at Screening, with >50% of the total score due to non-ocular symptoms
- •If receiving ≥1 of the following gMG treatments, on a stable dose of: • Acetylcholinesterase inhibitors (no dose change for 2 weeks prior to Screening) • Steroids (at least 3 months of treatment, no dose change for 1 month prior to Screening) • Non-steroidal immunosuppressive therapy (NSIST) including mycophenolate mofetil (MMF), methotrexate, cyclosporine, tacrolimus or cyclophosphamide (at least 6 months of treatment, no dose change for 3 months prior to Screening) • Azathioprine (AZA) or cladribine (at least 6 months of treatment, no dose change for at least 2 months prior to Screening)
- •Patients have received all age-appropriate vaccinations per local or professional guidelines for immunocompromised individuals, per Investigator judgement
- •Women of childbearing potential who are heterosexually active must use an acceptable form of contraception from Screening through 60 days after the last dose of Study drug • Acceptable highly effective methods include: combined (estrogen- and progestogen-containing) oral, intravaginal or transdermal hormonal contraception (associated with inhibition of ovulation); progestogen-only oral, injectable or implantable hormonal contraception (associated with inhibition of ovulation); intrauterine device; intrauterine hormone-releasing system; bilateral tubal ligation or occlusion; abstinence; or intercourse with a male partner who has had a vasectomy with medical confirmation of surgical success. • In regions where highly effective contraception is not required per regulatory mandate or local standard practice, additional acceptable methods include: progestogen-only oral, injectable or implantable hormonal contraception (where inhibition of ovulation is not the primary mode of action); male or female condom with or without spermicide; cap, diaphragm or sponge with spermicide; or a combination of male condom with either cap, diaphragm or sponge with spermicide (double barrier methods).
- •Men with a female partner of childbearing potential must use an acceptable form of contraception from Screening through 150 days after the last dose of Study drug • Acceptable methods include: male condoms; abstinence; or vasectomy with medical confirmation of surgical success. • Additionally, it is recommended that female partners of childbearing potential utilize an acceptable method of contraception (as described above).
- •Men must agree to not donate sperm during the Study and for 150 days after receiving the last dose of Study drug
- •Able and willing to comply with the requirements and restrictions of the Study protocol
排除标准
- •MGFA Class I and Class V patients
- •Worsening muscle weakness secondary to concurrent infections or medications (aminoglycosides, fluoroquinolones, beta-blockers, etc.)
- •Autoimmune disease other than MG (eg, autoimmune thyroiditis, rheumatoid arthritis) that would interfere with an accurate assessment of clinical symptoms
- •Have received any B cell-targeted therapy including: • blisibimod, belimumab, inebilizumab or rituximab within 12 months prior to Screening; or • ocrelizumab within 18 months prior to Screening
- •Have received treatment with complement inhibitor (eg, eculizumab, ravulizumab, zilucoplan) within 3 months prior to Screening
- •Have received FcRn blockers (eg, efgartigimod alfa, rozanolixizumab-noli, nipocalimab) within 3 months prior to Screening
- •Have received immunoglobulins given by IV (IVIg), subcutaneous or intramuscular route, or plasma exchange (PLEX), within 1 month prior to Screening
- •Thymectomy performed within 3 months prior to Screening or planned to be performed during the Study
- •Known or suspected allergy or hypersensitivity, intolerance or contraindication to any component of aritinercept or history of severe hypersensitivity reaction to any monoclonal antibody
- •Pregnant, breastfeeding or intending to become pregnant during the Study
- •Clinically significant electrocardiogram (ECG) abnormalities at Screening or on Day 1, defined as any of the following: • Average QT interval corrected according to Fridericia’s formula (QTcF) of 3 ECGs ≥450 msec for males and ≥470 msec for females; • Evidence of second- and third-degree atrioventricular (AV) block, complete left bundle branch block (LBBB) or complete right bundle branch block (RBBB); • Features of new ischemia; • Arrhythmia (except premature atrial contractions [PACs] and premature ventricular contractions [PVCs])
- •Clinically significant liver and/or renal impairment, defined as any of the following: • Alanine aminotransferase (ALT) >2 × upper limit of normal (ULN) • Aspartate aminotransferase (AST) >2 × ULN • Total bilirubin >1.5 × ULN; does not apply to patients with Gilbert’s syndrome • Serum creatinine >ULN
- •History of hypogammaglobulinemia or serum IgG, IgM or IgA concentrations below the lower limit of normal at Screening
- •Have uncontrolled diabetes defined as hemoglobin-A1c value >7.5%
- •Blood drawn (>300 mL) within 30 days prior to Screening or receipt of blood products within 30 days prior to Day 1
- •Have required recent management of acute or chronic infection as follows: • Currently on any suppressive therapy for a chronic infection (eg, tuberculosis [TB], pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria); • Hospitalization for treatment of infection within 60 days prior to Screening; • Use of parenteral (intravenous or intramuscular) antibiotics (antibacterials, antivirals, anti-fungals or anti-parasitic agents) within 60 days prior to Screening
- •Recent live vaccination (within 28 days prior to first dose of Study drug) or planned live vaccination during the Study or within 6 weeks after the last dose of Study drug
- •Known positive COVID-19 test result within 7 days prior to Day 1
- •Prior treatment with aritinercept
- •History of alcohol and/or other substance (except caffeine or nicotine) abuse within 1 year prior to Screening
- •Current or medical history of any of the following: • Congenital or acquired immunodeficiency (eg, IgA deficiency); • Demyelinating disease such as, but not restricted to, multiple sclerosis, optic neuritis, transverse myelitis or acute or chronic demyelinating polyneuropathy; • Malignancy within 5 years prior to Screening, with the exception of treated patients who are considered cured with at least a 2-year period of remission prior to Screening and minimal risk of recurrence; • Lymphoproliferative disease or previous total lymphoid irradiation; • Active, chronic or severe viral infections (eg, cytomegalovirus, hepatitis B virus, hepatitis C virus) within 3 months prior to Screening. Severe viral infection is defined as active disease requiring antiviral therapy. Patients who test positive for hepatitis B surface antigen and/or hepatitis C at Screening will be excluded; • Active TB or known history of TB. Patients should have a negative TB test with the result reported prior to Day
- •Indeterminate results may be repeated. • Antiphospholipid syndrome or antiphospholipid antibodies at Screening; • History of human immunodeficiency virus (HIV) infection or demonstration of HIV antibodies at Screening
- •Have active central nervous system (CNS) lupus (including seizures, psychosis, organic brain syndrome, cerebrovascular accident [CVA], cerebritis or CNS vasculitis) requiring therapeutic intervention within 60 days prior to Screening
- •Patients with a history or current evidence of any other cardiac, hepatic, renal, pulmonary, endocrine, neurologic, gastrointestinal, hematologic, oncologic or psychiatric disease as determined by medical/disease history, physical examination, laboratory reports, 12-lead ECG or any findings that, in the view of the Investigator or the Study Medical Team, would compromise the patient’s safety or affect Study conduct
- •Uncontrolled hypotension (systolic blood pressure <100 mmHg or diastolic blood pressure <60 mmHg)
- •Any condition or circumstances that, in the opinion of the Investigator, may make a patient unlikely or unable to complete the Study or comply with the Study procedures and requirements
- •Patient is an employee of the Investigator or Study site, with direct involvement in the Study or other studies under the direction of that Investigator or Study site, as well as family members of the employees or the Investigator
研究组 & 干预措施
Isotone Natriumchloridlösung 0,9 % Braun Injektionslösung
Placebo
干预措施: Isotone Natriumchloridlösung 0,9 % Braun Injektionslösung (Drug)
AUR200
Test
干预措施: AUR200 (Drug)
结局指标
主要结局
Phase 1: Incidence of treatment-emergent adverse events; Phase 2: Change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) total score
Phase 1: Incidence of treatment-emergent adverse events; Phase 2: Change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) total score
次要结局
- Aritinercept serum concentrations over time
- Change from baseline in serum levels of IgG, IgM and IgA
- Incidence of aritinercept anti-drug antibodies
研究者
Clinical Trial Inquiries
Scientific
Aurinia Pharmaceuticals Inc.
研究点 (12)
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