Clinical trial NCT06044350: A Clinical Trial of BAT4406F Injection in Patients with Neuromyelitis Optica Spectrum Disorders
Official title: A Phase II/III Study to Evaluate the Efficacy and Safety of BAT4406F Injection in Patients with Neuromyelitis Optica Lineage Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Optic Neuromyelitis Spectrum Disease
Lead sponsor: Bio-Thera Solutions
Sponsor class: INDUSTRY
First posted: 2023-09-21
Enrollment: 162
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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) .

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Age greater than or equal to the age of 18 and less than or equal to 65 patients, gender not limited;
2. Met the 2015 international NMO diagnostic panel (IPND) criteria for NMOSD, And AQP4-IGG positive patients
3. 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
4. For subjects who had a relapse before screening, symptoms needed to be stable for at least 4 weeks before randomization
5. 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
6. The score of EDSS 7 or less
7. Has the fertility of men and women must agree during treatment and 6 months after the last dose of using effective birth control method;
8. Agreed to participate in trials, and books to sign the informed consent

Exclusion Criteria:

1. 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.) ;
2. 6 months prior to the baseline used other monoclonal antibody therapy;Baseline used within five half-life before other biological preparation;
3. 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
4. Within a month before the filter used intravenous immunoglobulin (IVIG), plasma exchange (PE);
5. 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
6. 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);
7. 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；
8. 6 months prior to screening, except NMOSD need continuous oral or intravenous glucocorticoid dose \> 20 mg/day of any more than 21 days
9. Abnormal liver, kidney and bone marrow reserve
10. 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;
11. Comply with any of the following subjects a latent or active TB infection related standards:

    1. Current or past people with active TB;
    2. In history and/or physical examination during filter tip physical signs or symptoms of active TB;
    3. Recent close contact with people with active TB;
    4. 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.
12. 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;
13. 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;
14. 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；
15. 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) ;
16. Pregnant or lactating women, and screening or baseline pregnancy test positive female subjects;
17. Researchers think that the other does not fit to participate in this study.

Primary outcomes:
measure: Pharmacodynamics
timeFrame: RCP: Day7, Day14, Day28, Day56, Day84, Day112, Day140, Day182, Day280, Day364. OLP:D7, D28, Day84, Day182, Day280, Day364. Week 40+26n (n=1, 2, 3.....) , Week 52+26n (n=1, 2, 3.....). And OLP maximum period for 3 years
measure: Pharmacodynamics
timeFrame: RCP:in Day84、Day182、Day280、Day364. OLP: in Day1、Day84、Day182、Day280、Day364 of every years.And OLP maximum period for 3 years
measure: Pharmacodynamics
timeFrame: RCP:in Day84、Day182、Day280、Day364. OLP: in Day1、Day84、Day182、Day280、Day364 of every years.And OLP maximum period for 3 years
measure: Pharmacokinetics（PK）
timeFrame: Through study completion,up to 49 months. And OLP maximum period for 3 years.
measure: Pharmacokinetics（PK）
timeFrame: Through study completion,up to 49 months. And OLP maximum period for 3 years.
measure: Pharmacokinetics（PK）
timeFrame: Through study completion,up to 49 months. And OLP maximum period for 3 years.
measure: Pharmacokinetics（PK）
timeFrame: Through study completion,up to 49 months. And OLP maximum period for 3 years.
measure: Pharmacokinetics（PK）
timeFrame: Through study completion,up to 49 months. And OLP maximum period for 3 years.
measure: Pharmacokinetics（PK）
timeFrame: Through study completion,up to 49 months. And OLP maximum period for 3 years.
measure: Pharmacokinetics（PK）
timeFrame: Through study completion,up to 49 months. And OLP maximum period for 3 years.
measure: Immunogenicity evaluation
timeFrame: RCP:in Day84、Day181、Day252、Day364. OLP: in Day84、Day181、Day252、Day364 of every years.And OLP maximum period for 3 years
measure: Immunogenicity evaluation
timeFrame: RCP:in Day84、Day181、Day252、Day364. OLP: in Day84、Day181、Day252、Day364 of every years.And OLP maximum period for 3 years
Secondary outcomes:
measure: Vital signs
timeFrame: Through study completion,up to 49 months. And OLP maximum period for 3 years.
measure: physical examination
timeFrame: Through study completion,up to 49 months. And OLP maximum period for 3 years.
measure: Laboratory tests
timeFrame: Through study completion,up to 49 months. And OLP maximum period for 3 years.
measure: electrocardiogram（ ECG ）
timeFrame: Through study completion,up to 49 months. And OLP maximum period for 3 years.
measure: Adverse events（AE）
timeFrame: Through study completion,up to 49 months. And OLP maximum period for 3 years.
measure: Injection site reactions
timeFrame: Through study completion,up to 49 months. And OLP maximum period for 3 years.
Other outcomes:
Locations:
city: Baotou
country: China
facility: The First Affiliated Hospital of the Baotou Medical College of Inner Mongolia University of Science and Technology
city: Beijing
country: China
facility: Beijing Hospital
city: Beijing
country: China
facility: China-japan friendship Hospital
city: Beijing
country: China
facility: The first hospital of Peking University
city: Changsha
country: China
facility: The Central South University Xiang Ya Hospital
city: Changsha
country: China
facility: Xiangya 2nd hospital of central south university
city: Chongqing
country: China
facility: First affiliated hospital of chongqing medical university
city: Dalian
country: China
facility: The first affiliated hospital of Dalian Medical University
city: Fuzhou
country: China
facility: First affiliated hospital of fujian medical university
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital, Sun Yat-sen University
city: Guangzhou
country: China
facility: The first hospital affiliated to sun yat-sen university
city: Guangzhou
country: China
facility: The first People's Hospital of Guangzhou
city: Guangzhou
country: China
facility: The third hospital affiliated to sun yat-sen university
city: Hangzhou
country: China
facility: People's Hospital of Zhejiang province
city: Hefei
country: China
facility: Anhui Provincial Hospital
city: Hefei
country: China
facility: Second Affiliated Hospital of Anhui Medical University
city: Jinan
country: China
facility: Shandong University Qilu Hospital
city: Jingzhou
country: China
facility: Jingzhou Central Hospital
city: Kunming
country: China
facility: First Affiliated Hospital of the Kunming Medical University
city: Nanchang
country: China
facility: Second Affiliated Hospital of Nanchang University
city: Nanchong
country: China
facility: Affiliated Hospital of North Sichuan Medical College
city: Nanjing
country: China
facility: Drum Tower Hospital affiliated to Medical College of Nanjing University
city: Nanjing
country: China
facility: Southeast university affiliated zhongda hospital
city: Nanjing
country: China
facility: The Chinese people's liberation army general hospital in eastern theater
city: Nantong
country: China
facility: The first People's Hospital of Nantong
city: Qingdao
country: China
facility: Qingdao municipal hospital
city: Shanghai
country: China
facility: Mount Hua Hospital affiliated to Fudan University
city: Shanghai
country: China
facility: Shuguang hospital affiliated to Shanghai University of Traditional Chinese medicine
city: Shanghai
country: China
facility: Zhongshan hospital affiliated to Fudan University
city: Shenzhen
country: China
facility: Shenzhen city people's hospital
city: Shijia Zhuang
country: China
facility: Second Hebei Medical University Hospital
city: Shijiazhuang
country: China
facility: The Third Hospital of Hebei Medical University
city: Suzhou
country: China
facility: First Affiliated Hospital of Suzhou University
city: Suzhou
country: China
facility: The Second Affiliated Hospital of Suzhou University
city: Taiyuan
country: China
facility: The first hospital of shanxi medical university
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
city: Wenzhou
country: China
facility: The first hospital affiliated to wenzhou medical college
city: Wuhan
country: China
facility: Tongji hospital affiliated to tongji medical college huazhong university of science and technology
city: Wuhan
country: China
facility: Xiehe hospital affiliated to tongji medical college huazhong university of science and technology
city: Wuxi
country: China
facility: Wuxi city people's hospital
city: Xi'an
country: China
facility: Second Affiliated Hospital of the People's Liberation Army Air Force Military Medical University
city: Xi'an
country: China
facility: Xi'an high-tech Hospital Co. , Ltd.
city: Xianyang
country: China
facility: Yan 'an University Xianyang Hospital Co. , Ltd.
city: Zhengzhou
country: China
facility: Henan province people's hospital
city: Zhenzhou
country: China
facility: Zhengzhou university first affiliated hospital
Study officials:
affiliation: Huashan Hospital
name: Xiangjun Chen, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Second Affiliated Hospital of Suzhou University
name: Chunfeng Liu, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: First Affiliated Hospital of Suzhou University
name: Qun Xue, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Anhui Provincial Hospital
name: Yan Jiang, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Shandong University Qilu Hospital
name: Yuying Zhao, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Second Hebei Medical University Hospital
name: Li Guo, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Affiliated Hospital of Shanxi Medical University
name: Meini Zhang, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The Central South University Xiang Ya Hospital
name: Huan Yang, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Tongji hospital affiliated to Tongji Medical College
name: Daishi Tian, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Affiliated Hospital of Zhengzhou University
name: Yuming Xu, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Second Affiliated Hospital of Nanchang University
name: Jianglong Tu, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The third hospital affiliated to sun yat-sen university
name: Wei Qiu, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: Yamei Tang, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The First People's Hospital of Guangzhou
name: Honghao Wang, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Shenzhen city people's hospital
name: Xiaoling Luo, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: First Affiliated Hospital of Fujian Medical University
name: Aiyu Lin, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: China University Hospital of Southeast University
name: Chunming Xie, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The first hospital affiliated to wenzhou medical college
name: Xiang Li, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Qingdao City Hospital
name: Lan Tan, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Tianjin Medical University General Hospital
name: Fudong Shi, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Afﬁliated Hospital of North Sichuan Medical College
name: Juming Yu, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The Second Affiliated Hospital of the PLA Air Force Military Medical University
name: Jun Guo, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Henan Provincial People's Hospital
name: Jiewen Zhang, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Second Affiliated Hospital of Anhui Medical University
name: Yanghua Tian, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Shanghai Zhongshan Hospital
name: Jing Ding, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Xianyang yanan university hospital co., LTD
name: Ping Chen, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Xi'an high-tech Hospital Co. , Ltd.
name: Zunbo Li, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Jingzhou city central hospital
name: Qihe Dai, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: the first hospital of Baotou medicine college
name: Dan Liu, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Hebei Medical University Third Hospital
name: Junyan Liu, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Zhejiang Province People's Hospital
name: Yiqi Wang, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Xiehe hospital affiliated to tongji medical college
name: Bo Hu, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: First Affiliated Hospital of the Kunming Medical University
name: Yanbing Han, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Wuxi city people's hospital
name: Feng Wang, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Affiliated Hospital of Dalian Medical University
name: Zhanhua Liang, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Sino-Japanese Friendship Hospital
name: Weihe Zhang, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Nantong First People's Hospital
name: Xiangyang Zhu, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The Chinese people's liberation army general hospital in eastern theater
name: Xinfeng Liu, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine
name: Weidong Pan, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The Central South University Xiang YA II hospital
name: Wei Lu, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The first hospital affiliated to sun yat-sen university
name: Huiyu Feng, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The first hospital of Peking University
name: Feng Gao, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Drum tower hospital affiliated to nanjing university school of medicine
name: Yun Xu, Doctor
role: PRINCIPAL_INVESTIGATOR
References: