Clinical Study of B001 Injection in Subjects With Neuromyelitis Optic Spectrum Disorder (NMOSD)

Study Overview
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Brief Summary
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The objectives of this phase Ib study are to evaluate the efficacy, safety, pharmacokinetics, pharmacodynamics and immunogenic profiles of B001 in subjects with aquaporin-4 antibody (AQP4-IgG) positive NMOSD.

Official Title
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A Phase Ib Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of B001 in Subjects With Aquaporin-4 Antibody (AQP4-IgG) Positive Neuromyelitis Optic Spectrum Disorder (NMOSD)

Conditions
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NMO Spectrum Disorder

Intervention / Treatment
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* Drug: B001 injection
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: NMOSD as defined by either of the following 2015 criteria with anti-AQP4 antibody (Ab) seropositive status at screening Clinical evidence of at least 1 documented relapse in last 12 months prior to screening Expanded Disability Status Scale (EDSS) score from 0 to 7.5 inclusive at screening Age 18 to 70 years, inclusive at the time of informed consent Exclusion Criteria: Any previous treatment with anti-CD20, eculizumab, anti-BLyS monoclonal antibody (e.g., belimumab), any other treatment for prevention of multiple sclerosis (MS) relapse (e.g., interferon, natalizumab, glatiramer acetate, fingolimod, teriflunomide or dimethyl fumarate) within 6 months prior to baseline. Received immunosuppression such as azathioprine, mycophenolate mofetil, methotrexate, cyclophosphamide, tacrolimus, mitoxantrone, cyclosporine A, etc, and rug therapy, biological agents such as satralizumab, tocilizumab, eculizumab, etc, 3 months prior to the first administration. Evidence of serious uncontrolled concomitant diseases that may preclude participant participation, as described; Other nervous system disease, cardiovascular disease, hematologic/hematopoiesis disease, respiratory disease, muscular disease, endocrine disease, renal/urologic disease, digestive system disease, congenital or acquired severe immunodeficiency. Known active infection within 3 months prior to baseline Pregnancy or lactation. History of severe allergic reaction to a biologic agent Evidence of chronic active hepatitis B or C Evidence of active tuberculosis Following laboratory abnormalities at screening*: White blood cells (WBC) <4.0 x10^3/microliter (μL) Absolute neutrophil count (ANC) Absolute lymphocyte count <0.5 x10^3/μL Platelet count <80 x 10^9/ L Aspartate aminotransferase (AST) or alanine aminotransferase History of drug or alcohol abuse within 6 months prior to baseline Receipt of any live or live attenuated vaccine within 4 weeks prior to baseline Uncontrolled systemic diseases, including hypertension that cannot be effectively controlled after treatment (systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥100 mmHg), diabetes, gastrointestinal diseases, etc.; or the investigator believes that there is anything inappropriate reasons for selection.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: B001 injection<br>Subjects randomized to this arm will receive B001 twice, at day 1 and day 15, up to the end of the study. | Drug: B001 injection<br>* B001 injection 50mg/5mL Intravenous solution<br>|
| Placebo Comparator: Placebo<br>Subjects randomized to this arm will receive Placebo twice, at day 1 and day 15, up to the end of the study. | Biological: Placebo<br>* Placebo 5mL Intravenous solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity (DLT) | Measurement of DLT in all subjects. | Up to 18 days. | 
| Evaluate incidence of treatment-emergent adverse events [Safety and Tolerability]. |  | Up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum serum concentration (Cmax) of B001. | To characterize the PK (Pharmacokinetics) of B001. | Through study completion, up to 2 years | 
| Time of maximum serum concentration (Tmax) of B001. | To characterize the PK (Pharmacokinetics) of B001. | Through study completion, up to 2 years | 
| Area under the serum concentration-time curve (AUC) of the Dosing Interval (0-14D) of B001. | To characterize the PK (Pharmacokinetics) of B001. | Through study completion, up to 2 years | 
| Area under the serum concentration-time curve (AUC) of the Dosing Interval (0-Last) of B001. | To characterize the PK (Pharmacokinetics) of B001. | Through study completion, up to 2 years | 
| Area under the serum concentration-time curve (AUC) of the Dosing Interval (0-infinity) of B001. | To characterize the PK (Pharmacokinetics) of B001. | Through study completion, up to 2 years | 
| Accumulation ratio of maximum serum concentration (Rac_Cmax) of B001. | To characterize the PK (Pharmacokinetics) of B001. | Through study completion, up to 2 years | 
| Accumulation ratio of area under the serum concentration-time curve (Rac_AUC) of the Dosing Interval (0-14D) of B001. | To characterize the PK (Pharmacokinetics) of B001. | Through study completion, up to 2 years | 
| Terminal rate constant(λz) of B001. | To characterize the PK (Pharmacokinetics) of B001. | Through study completion, up to 2 years | 
| Half-life (t1/2) of B001. | To characterize the PK (Pharmacokinetics) of B001. | Through study completion, up to 2 years | 
| Total clearance(CL) of B001. | To characterize the PK (Pharmacokinetics) of B001. | Through study completion, up to 2 years | 
| Volume of distribution(Vz) of B001. | To characterize the PK (Pharmacokinetics) of B001. | Through study completion, up to 2 years | 
| Percentage of area under the serum concentration-time curve (AUC 0-infinity) obtained by extrapolation (%AUCex) of B001. | To characterize the PK (Pharmacokinetics) of B001. | Through study completion, up to 2 years | 
| Percentage of subjects with ADA to B001 and neutralizing resistance (Nab) |  | Through study completion, up to 2 years | 
| Time to First Protocol-Defined Relapse (TFR) in the Double-Blind Period |  | Through study completion, up to 2 years | 
| Change in Expanded Disability Status Scale (EDSS) Score | The EDSS provides a total score on a scale that ranges from 0 to 10 in 0.5 increments that represent higher levels of disability. Increasing disability is reflected in an increasing EDSS score. | Through study completion, up to 2 years | 
| Time to EDSS Worsening |  | Through study completion, up to 2 years |