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

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)

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.

Study Overview

• Status: Recruiting
• Conditions: NMO Spectrum Disorder
• Intervention / Treatment: Drug: B001 injection; Biological: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Fu-Dong Shi, MD,PhD; Phone Number: 022-60814587; Email: Shifudong219@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100050
      • Recruiting
      • Beijing Tiantan Hospital Capital Medical University
      • Contact: Yunxing Song; Phone Number: +86 17813230827; Email: songyx@sphchina.com
      • Principal Investigator: Xinghu Zhang
  • Shanxi
    • Taiyuan, Shanxi, China, 030001
      • Recruiting
      • First Hospital Of ShanXi Medical University
      • Contact: Yunxing Song; Phone Number: +86 17813230827; Email: songyx@sphchina.com
      • Principal Investigator: Meini Zhang
    • Xi'an, Shanxi, China, 710038
      • Recruiting
      • Tangdu hospital,fourth military medical university
      • Contact: Shicao Li; Phone Number: 0086-029-84717761; Email: tangduec@126.com
      • Principal Investigator: Jun Guo
  • Tianjin
    • Tianjin, Tianjin, China, 300052
      • Recruiting
      • Tianjin Medical University General Hospital
      • Contact: Chao Zhang, MD; Phone Number: 022-60814587; Email: chaozhang@tmu.edu.can
      • Principal Investigator: Fu-Dong Shi, MD,PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. NMOSD as defined by either of the following 2015 criteria with anti-AQP4 antibody (Ab) seropositive status at screening
2. Clinical evidence of at least 1 documented relapse in last 12 months prior to screening
3. Expanded Disability Status Scale (EDSS) score from 0 to 7.5 inclusive at screening
4. Age 18 to 70 years, inclusive at the time of informed consent

Exclusion Criteria:

1. 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.
2. 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.
3. 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.
4. Known active infection within 3 months prior to baseline
5. Pregnancy or lactation.
6. History of severe allergic reaction to a biologic agent
7. Evidence of chronic active hepatitis B or C
8. Evidence of active tuberculosis

9. Following laboratory abnormalities at screening*:

   1. White blood cells (WBC) <4.0 x10^3/microliter (μL)
   2. Absolute neutrophil count (ANC)
   3. Absolute lymphocyte count <0.5 x10^3/μL
   4. Platelet count <80 x 10^9/ L
   5. Aspartate aminotransferase (AST) or alanine aminotransferase
10. History of drug or alcohol abuse within 6 months prior to baseline
11. Receipt of any live or live attenuated vaccine within 4 weeks prior to baseline
12. 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Shanghai Pharmaceuticals Holding Co., Ltd
• Investigators: Principal Investigator: Fu-Dong Shi, MD,PhD, Tianjin Medical University General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2022
• Primary Completion (Estimated): April 15, 2024
• Study Completion (Estimated): December 15, 2024

Study Registration Dates

• First Submitted: November 21, 2021
• First Submitted That Met QC Criteria: December 2, 2021
• First Posted (Actual): December 6, 2021

Study Record Updates

• Last Update Posted (Actual): January 5, 2024
• Last Update Submitted That Met QC Criteria: January 3, 2024
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Eye Diseases; Optic Nerve Diseases; Cranial Nerve Diseases; Myelitis, Transverse; Optic Neuritis; Neuromyelitis Optica
• Other Study ID Numbers: B001-103

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No