A Phase II/III Study to Evaluate the Efficacy and Safety of BAT4406F Injection in Patients With Neuromyelitis Optica Lineage Disease
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 162
- 试验地点
- 45
- 主要终点
- Pharmacokinetics（PK）
研究概览
简要总结
This is a phase II/III multicenter, randomized, double-blind, placebo-controlled study, to investigate the efficacy and safety of BAT4406F injection in patients with neuromyelitis optica lineage disease (NMOSD) who are positive for aquaporin 4 antibody (AQP4-IgG) .
详细描述
This study was a phase II/III multicenter, randomized, double-blind, placebo-controlled study, which was divided into screening period (4 weeks) , randomized control period (RCP) , and open-label period (Olp)A total of 162 subjects were enrolled during the screening period and randomly assigned 2:1 to either the BAT4406F group or the placebo group after randomization on Day 1 of the RCP, subjects would receive BAT4406F (at a dose of 500mg) or placebo, intravenously, at D 1 and D 182, respectively.
If any of the following conditions occur, subjects can enter OLP from RCP: 1. Subjects who complete the 52-week RCP study without recurrence of NMOSD can enter Olp within 14 days after the end of the RCP study. 2. In the stage of RCP, NMOSD recurred. After rescue therapy, the patients with stable condition could enter OLP within 28 days after diagnosis. Subjects continued to participate in the RCP study if they were not identified by CEC as having a relapse upon examination. 3. When a protocol-defined first relapse event of 35 cases is observed, or when all 162 subjects have completed randomization and 12 months have elapsed since the first dose in the last of these subjects, or when recommended by the Independent Data Monitoring Committee (IDMC) , the RCP study should be stopped for enrolled subjects, and all enrolled subjects at the RCP stage should stop the RCP study within 14 days of entry into OLP, after which subjects will receive BAT4406F injection at the same dose as RCP, at d 1 of OLP. After termination of the RCP study with BAT4406F every 6 months, subjects were given the option of enrolling in the OLP study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age greater than or equal to the age of 18 and less than or equal to 65 patients, gender not limited;
- •Met the 2015 international NMO diagnostic panel (IPND) criteria for NMOSD, And AQP4-IGG positive patients
- •Screening before 2 times at least 2 years experience with clinical records of relapse，or experienced at least 1 clinically documented recurrence within 1 year prior to screening
- •For subjects who had a relapse before screening, symptoms needed to be stable for at least 4 weeks before randomization
- •Into the group of former dosage of corticosteroids under 30 mg and prednisone equivalent，and the trial drug must be used within a month after the withdrawal of hormones
- •The score of EDSS 7 or less
- •Has the fertility of men and women must agree during treatment and 6 months after the last dose of using effective birth control method;
- •Agreed to participate in trials, and books to sign the informed consent
排除标准
- •CD19 + b-cell count below the lower limit of normal, b-cell-scavenger drugs used 6 months before baseline or within 5 half-lives of the drug, whichever is older (including but not limited to Rituximab, enalizumab, etc.) ;
- •6 months prior to the baseline used other monoclonal antibody therapy;Baseline used within five half-life before other biological preparation;
- •Used it for 3 months prior to the baseline McCaw phenol ester, azathioprine and methotrexate;6 months prior to the baseline using cyclophosphamide;Baseline before five half-life
- •Within a month before the filter used intravenous immunoglobulin (IVIG), plasma exchange (PE);
- •Within 4 weeks before screening received vaccine or live attenuated;Within 2 weeks before the baseline received inactivated vaccine;Baseline received within 4 weeks before the new coronavirus vaccine
- •In another clinical study and the baseline from the test drug treatment under three months or 5 half-life of the drug (the long time limit shall prevail);
- •This test for monoclonal antibody has a history of allergies, known in drug allergy patients;Serious drug allergy or for two or over two kinds of food or drugs；
- •6 months prior to screening, except NMOSD need continuous oral or intravenous glucocorticoid dose > 20 mg/day of any more than 21 days
- •Abnormal liver, kidney and bone marrow reserve
- •HIV positive at HIV history or enrollment screening; History of hepatitis B Andor hepatitis C or Hepatitis B surface antigen (HBSAG) positivity at screening [ or Hepatitis B core antibody positive, hepatitis B surface antibody negative, Hepatitis B virus deoxynucleotides (HBV DNA) quantification exceeding normal range ] ; Or Hepatitis C virus (HCV) antibody positive [ with HCV-rna quantitation exceeding the normal range ] , Treponema pallidum antibody positive at the time of enrollment;
- •Comply with any of the following subjects a latent or active TB infection related standards:
- •Current or past people with active TB;
- •In history and/or physical examination during filter tip physical signs or symptoms of active TB;
- •Recent close contact with people with active TB;
- •At the time of screening, the positive result of TB infected T cells was found. A test could be repeated if the subject's first tb-infected t-cell test result was inconclusive, and the patient was excluded from this study if the test result was inconclusive (or positive) again.
- •Covid-19 infection was diagnosed with clinical symptoms or signs consistent with 2019 coronavirus (COVID-19) infection (eg, fever, dry cough, dyspnea, sore throat, and fatigue) within 4 weeks before screening or during screening, or upon appropriate laboratory testing (at the discretion of the investigator or in accordance with local regulations) . If COVID-19 infection is confirmed before screening, appropriate laboratory testing is required to confirm that the infection has been cured;
- •Suffering from metabolic, hematological, renal, hepatic, pulmonary, neuroendocrine, cardiac, infectious, gastrointestinal or other autoimmune diseases, the researchers believe there is an unacceptable risk to patients, or it may affect NMOSD assessment;
- •According to the researchers, there was a history of drug and alcohol abuse (drinking 14 units of alcohol per week: 1 unit = 285 mL of beer, or 25 mL of spirits, or 125 mL of wine) in the 12 months before screening；
- •Subjects who are unable to undergo an MRI scan (for example, are allergic to Gd-containing MRI contrast media, have a pacemaker, defibrillator, or other metallic object with internal or external limitations to performing an MRI scan) ;
- •Pregnant or lactating women, and screening or baseline pregnancy test positive female subjects;
- •Researchers think that the other does not fit to participate in this study.
研究组 & 干预措施
Experimental group：BAT4406F
RCP：Intravenous infusion; Dosage:500mg/time; Time of administration:The drug was given at D 1 and D 182 respectively OLP：Intravenous infusion; Dosage:500mg/time; Time of administration: After D1 dosing, Every 6 months to 1 times
干预措施: BAT4406F Injection (Drug)
Control group：BAT4406F Placebos
RCP：Intravenous infusion; Dosage:500mg/time; Time of administration:The drug was given at D 1 and D 182 respectively OLP：Intravenous infusion; Dosage:500mg/time; Time of administration: After D1 dosing, Every 6 months to 1 times
干预措施: BAT4406F Placebos (Drug)
结局指标
主要结局
Pharmacokinetics（PK）
时间窗: Through study completion,up to 49 months. And OLP maximum period for 3 years.
Vd
Immunogenicity evaluation
时间窗: RCP:in Day84、Day181、Day252、Day364. OLP: in Day84、Day181、Day252、Day364 of every years.And OLP maximum period for 3 years
The titers of Ada positive samples
Pharmacodynamics
时间窗: RCP:in Day84、Day182、Day280、Day364. OLP: in Day1、Day84、Day182、Day280、Day364 of every years.And OLP maximum period for 3 years
AQP4-IgG levels were measured.
次要结局
- Adverse events（AE）(Through study completion,up to 49 months. And OLP maximum period for 3 years.)
- physical examination(Through study completion,up to 49 months. And OLP maximum period for 3 years.)
- Vital signs(Through study completion,up to 49 months. And OLP maximum period for 3 years.)
- electrocardiogram（ ECG ）(Through study completion,up to 49 months. And OLP maximum period for 3 years.)
- Laboratory tests(Through study completion,up to 49 months. And OLP maximum period for 3 years.)
- Injection site reactions(Through study completion,up to 49 months. And OLP maximum period for 3 years.)