A Clinical Trial of BAT4406F Injection in Patients With Neuromyelitis Optica Spectrum Disorders

A Phase II/III Study to Evaluate the Efficacy and Safety of BAT4406F Injection in Patients With Neuromyelitis Optica Lineage Disease

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) .

Study Overview

• Status: Active, not recruiting
• Conditions: Optic Neuromyelitis Spectrum Disease
• Intervention / Treatment: Drug: BAT4406F Injection; Drug: BAT4406F Placebos

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.

• Study Type: Interventional
• Enrollment (Estimated): 162
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Baotou, China
    • The First Affiliated Hospital of the Baotou Medical College of Inner Mongolia University of Science and Technology
  • Beijing, China
    • Beijing Hospital
  • Beijing, China
    • China-Japan Friendship Hospital
  • Beijing, China
    • The First Hospital of Peking University
  • Changsha, China
    • The Central South University Xiang Ya Hospital
  • Changsha, China
    • Xiangya 2nd hospital of central south university
  • Chongqing, China
    • First Affiliated Hospital of Chongqing Medical University
  • Dalian, China
    • The First Affiliated Hospital of Dalian Medical University
  • Fuzhou, China
    • First Affiliated Hospital of Fujian Medical University
  • Guangzhou, China
    • Sun Yat-sen Memorial Hospital, Sun Yat-sen University
  • Guangzhou, China
    • The First People's Hospital of Guangzhou
  • Guangzhou, China
    • The first hospital affiliated to sun yat-sen university
  • Guangzhou, China
    • The third hospital affiliated to sun yat-sen university
  • Hangzhou, China
    • People's Hospital of Zhejiang province
  • Hefei, China
    • Anhui Provincial Hospital
  • Hefei, China
    • Second Affiliated hospital of Anhui Medical University
  • Jinan, China
    • Shandong University Qilu Hospital
  • Jingzhou, China
    • Jingzhou Central Hospital
  • Kunming, China
    • First Affiliated Hospital of the Kunming Medical University
  • Nanchang, China
    • Second Affiliated Hospital of Nanchang University
  • Nanchong, China
    • Affiliated Hospital of North Sichuan Medical College
  • Nanjing, China
    • Drum Tower Hospital affiliated to Medical College of Nanjing University
  • Nanjing, China
    • Southeast University Affiliated Zhongda Hospital
  • Nanjing, China
    • The Chinese people's liberation army general hospital in eastern theater
  • Nantong, China
    • The First People's Hospital of Nantong
  • Qingdao, China
    • Qingdao Municipal Hospital
  • Shanghai, China
    • Zhongshan Hospital Affiliated to Fudan University
  • Shanghai, China
    • Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine
  • Shanghai, China
    • Mount Hua Hospital affiliated to Fudan University
  • Shenzhen, China
    • Shenzhen city people's hospital
  • Shijia Zhuang, China
    • Second Hebei Medical University Hospital
  • Shijiazhuang, China
    • The Third Hospital of Hebei Medical University
  • Suzhou, China
    • The Second Affiliated Hospital of Suzhou University
  • Suzhou, China
    • First Affiliated Hospital of Suzhou University
  • Taiyuan, China
    • The First Hospital of Shanxi Medical University
  • Tianjin, China
    • Tianjin Medical University General Hospital
  • Wenzhou, China
    • The first hospital affiliated to wenzhou medical college
  • Wuhan, China
    • Tongji hospital affiliated to tongji medical college huazhong university of science and technology
  • Wuhan, China
    • Xiehe hospital affiliated to tongji medical college huazhong university of science and technology
  • Wuxi, China
    • Wuxi city people's hospital
  • Xi'an, China
    • Second Affiliated Hospital of the People's Liberation Army Air Force Military Medical University
  • Xi'an, China
    • Xi'an high-tech Hospital Co. , Ltd.
  • Xianyang, China
    • Yan 'an University Xianyang Hospital Co. , Ltd.
  • Zhengzhou, China
    • Henan Province People's Hospital
  • Zhenzhou, China
    • Zhengzhou University First Affiliated Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: BAT4406F Injection; Intravenous infusion; Dosage:500mg/time
Active Comparator: 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	Drug: BAT4406F Placebos; Intravenous infusion; Dosage:500mg/time

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamics	The follow-up time point of peripheral blood before and after the analysis to the medicine CD19 + B lymphocytes proportion/count change	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
Pharmacodynamics	Serum immunoglobulin (IgG and IgM) levels were measured.	RCP:in Day84、Day182、Day280、Day364. OLP: in Day1、Day84、Day182、Day280、Day364 of every years.And OLP maximum period for 3 years
Pharmacodynamics	AQP4-IgG levels were measured.	RCP:in Day84、Day182、Day280、Day364. OLP: in Day1、Day84、Day182、Day280、Day364 of every years.And OLP maximum period for 3 years
Pharmacokinetics（PK）	Cmax	Through study completion,up to 49 months. And OLP maximum period for 3 years.
Pharmacokinetics（PK）	Tmax	Through study completion,up to 49 months. And OLP maximum period for 3 years.
Pharmacokinetics（PK）	Cmin	Through study completion,up to 49 months. And OLP maximum period for 3 years.
Pharmacokinetics（PK）	AUC0-tau	Through study completion,up to 49 months. And OLP maximum period for 3 years.
Pharmacokinetics（PK）	t1/2	Through study completion,up to 49 months. And OLP maximum period for 3 years.
Pharmacokinetics（PK）	CL	Through study completion,up to 49 months. And OLP maximum period for 3 years.
Pharmacokinetics（PK）	Vd	Through study completion,up to 49 months. And OLP maximum period for 3 years.
Immunogenicity evaluation	Resistant antibody positive rate (ADA)	RCP:in Day84、Day181、Day252、Day364. OLP: in Day84、Day181、Day252、Day364 of every years.And OLP maximum period for 3 years
Immunogenicity evaluation	The titers of Ada positive samples	RCP:in Day84、Day181、Day252、Day364. OLP: in Day84、Day181、Day252、Day364 of every years.And OLP maximum period for 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vital signs	Number of participants with abnormal vital signs	Through study completion,up to 49 months. And OLP maximum period for 3 years.
physical examination	Number of participants with abnormal physical examination findings	Through study completion,up to 49 months. And OLP maximum period for 3 years.
Laboratory tests	Number of participants with abnormal laboratory test results	Through study completion,up to 49 months. And OLP maximum period for 3 years.
electrocardiogram（ ECG ）	Number of participants with abnormal ECG readings	Through study completion,up to 49 months. And OLP maximum period for 3 years.
Adverse events（AE）	Adverse events (AE) is happening, is happening because of adverse events leading to withdrawal Adverse events associated with drugs The occurrence of Serious adverse events (SAE)	Through study completion,up to 49 months. And OLP maximum period for 3 years.
Injection site reactions	Number of participants with injection site reactions	Through study completion,up to 49 months. And OLP maximum period for 3 years.

Collaborators and Investigators

• Sponsor: Bio-Thera Solutions
• Investigators: Principal Investigator: Xiangjun Chen, Doctor, Huashan Hospital; Principal Investigator: Chunfeng Liu, Doctor, Second Affiliated Hospital of Suzhou University; Principal Investigator: Qun Xue, Doctor, First Affiliated Hospital of Suzhou University; Principal Investigator: Yan Jiang, Doctor, Anhui Provincial Hospital; Principal Investigator: Yuying Zhao, Doctor, Shandong University Qilu Hospital; Principal Investigator: Li Guo, Doctor, Second Hebei Medical University Hospital; Principal Investigator: Meini Zhang, Doctor, The First Affiliated Hospital of Shanxi Medical University; Principal Investigator: Huan Yang, Doctor, The Central South University Xiang Ya Hospital; Principal Investigator: Daishi Tian, Doctor, Tongji hospital affiliated to Tongji Medical College; Principal Investigator: Yuming Xu, Doctor, The First Affiliated Hospital of Zhengzhou University; Principal Investigator: Jianglong Tu, Doctor, Second Affiliated Hospital of Nanchang University; Principal Investigator: Wei Qiu, Doctor, The third hospital affiliated to sun yat-sen university; Principal Investigator: Honghao Wang, Doctor, The First People's Hospital of Guangzhou; Principal Investigator: Xiaoling Luo, Doctor, Shenzhen city people's hospital; Principal Investigator: Aiyu Lin, Doctor, First Affiliated Hospital of Fujian Medical University; Principal Investigator: Chunming Xie, Doctor, China University Hospital of Southeast University; Principal Investigator: Xiang Li, Doctor, The first hospital affiliated to wenzhou medical college; Principal Investigator: Lan Tan, Doctor, Qingdao City Hospital; Principal Investigator: Fudong Shi, Doctor, Tianjin Medical University General Hospital; Principal Investigator: Juming Yu, Doctor, Affiliated Hospital of North Sichuan Medical College; Principal Investigator: Jun Guo, Doctor, The Second Affiliated Hospital of The PLA Air Force Military Medical University; Principal Investigator: Jiewen Zhang, Doctor, Henan Provincial People's Hospital; Principal Investigator: Yanghua Tian, Doctor, Second Affiliated hospital of Anhui Medical University; Principal Investigator: Jing Ding, Doctor, Shanghai Zhongshan Hospital; Principal Investigator: Ping Chen, Doctor, Xianyang yanan university hospital co., LTD; Principal Investigator: Zunbo Li, Doctor, Xi'an high-tech Hospital Co. , Ltd.; Principal Investigator: Qihe Dai, Doctor, Jingzhou city central hospital; Principal Investigator: Dan Liu, Doctor, the first hospital of Baotou medicine college; Principal Investigator: Junyan Liu, Doctor, Hebei Medical University Third Hospital; Principal Investigator: Yiqi Wang, Doctor, Zhejiang Province People's Hospital; Principal Investigator: Bo Hu, Doctor, Xiehe hospital affiliated to tongji medical college; Principal Investigator: Yanbing Han, Doctor, First Affiliated Hospital of the Kunming Medical University; Principal Investigator: Feng Wang, Doctor, Wuxi city people's hospital; Principal Investigator: Zhanhua Liang, Doctor, The First Affiliated Hospital of Dalian Medical University; Principal Investigator: Weihe Zhang, Doctor, Sino-Japanese Friendship Hospital; Principal Investigator: Xiangyang Zhu, Doctor, Nantong First People's Hospital; Principal Investigator: Xinfeng Liu, Doctor, The Chinese people's liberation army general hospital in eastern theater; Principal Investigator: Weidong Pan, Doctor, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine; Principal Investigator: Wei Lu, Doctor, The Central South University Xiang YA II hospital; Principal Investigator: Huiyu Feng, Doctor, The first hospital affiliated to sun yat-sen university; Principal Investigator: Feng Gao, Doctor, The First Hospital of Peking University; Principal Investigator: Yun Xu, Doctor, Drum Tower Hospital affiliated to Nanjing University School of Medicine; Principal Investigator: Yamei Tang, Doctor, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2023
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2026

Study Registration Dates

• First Submitted: July 31, 2023
• First Submitted That Met QC Criteria: September 12, 2023
• First Posted (Actual): September 21, 2023

Study Record Updates

• Last Update Posted (Actual): December 8, 2025
• Last Update Submitted That Met QC Criteria: December 1, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Eye Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Myelitis, Transverse; Optic Neuritis; Optic Nerve Diseases; Cranial Nerve Diseases; Neuromyelitis Optica
• Other Study ID Numbers: BAT-4406F-002-CR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No