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

Early Phase 1

Recruiting

• Conditions: NMO Spectrum Disorder
• Interventions: Drug: B001 injection; Biological: Placebo

• Registration Number: NCT05145361
• Lead Sponsor: Shanghai Pharmaceuticals Holding Co., Ltd

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-11-21
• Study First Submitted QC: 2021-12-02
• Study First Posted: 2021-12-06
• Study Start: 2022-04-07
• Status Verified: 2024-06
• Last Update Submitted: 2025-01-24
• Last Update Posted: 2025-01-27
• Primary Completion: 2025-12-15
• Study Completion: 2025-12-15

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 45

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
B001 injection	B001 injection	Subjects randomized to this arm will receive B001 twice, at day 1 and day 15, up to the end of the study.
Placebo	Placebo	Subjects randomized to this arm will receive Placebo twice, at day 1 and day 15, up to the end of the study.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Time of maximum serum concentration (Tmax) of B001.	Through study completion, up to 2 years	To characterize the PK (Pharmacokinetics) of B001.
Maximum serum concentration (Cmax) of B001.	Through study completion, up to 2 years	To characterize the PK (Pharmacokinetics) of B001.
Terminal rate constant(λz) of B001.	Through study completion, up to 2 years	To characterize the PK (Pharmacokinetics) of B001.
Half-life (t1/2) of B001.	Through study completion, up to 2 years	To characterize the PK (Pharmacokinetics) of B001.
Percentage of area under the serum concentration-time curve (AUC 0-infinity) obtained by extrapolation (%AUCex) of B001.	Through study completion, up to 2 years	To characterize the PK (Pharmacokinetics) of B001.
Change in Expanded Disability Status Scale (EDSS) Score	Through study completion, up to 2 years	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.
Time to First Protocol-Defined Relapse (TFR) in the Double-Blind Period	Through study completion, up to 2 years
Accumulation ratio of maximum serum concentration (Rac_Cmax) of B001.	Through study completion, up to 2 years	To characterize the PK (Pharmacokinetics) of B001.
Area under the serum concentration-time curve (AUC) of the Dosing Interval (0-14D) of B001.	Through study completion, up to 2 years	To characterize the PK (Pharmacokinetics) of B001.
Area under the serum concentration-time curve (AUC) of the Dosing Interval (0-Last) of B001.	Through study completion, up to 2 years	To characterize the PK (Pharmacokinetics) of B001.
Area under the serum concentration-time curve (AUC) of the Dosing Interval (0-infinity) of B001.	Through study completion, up to 2 years	To characterize the PK (Pharmacokinetics) of B001.
Accumulation ratio of area under the serum concentration-time curve (Rac_AUC) of the Dosing Interval (0-14D) of B001.	Through study completion, up to 2 years	To characterize the PK (Pharmacokinetics) of B001.
Volume of distribution(Vz) of B001.	Through study completion, up to 2 years	To characterize the PK (Pharmacokinetics) of B001.
Percentage of subjects with ADA to B001 and neutralizing resistance (Nab)	Through study completion, up to 2 years
Total clearance(CL) of B001.	Through study completion, up to 2 years	To characterize the PK (Pharmacokinetics) of B001.
Time to EDSS Worsening	Through study completion, up to 2 years

Trial Locations

Locations (4)

Tangdu hospital,fourth military medical university; 🇨🇳 Xi'an, Shanxi, China

Beijing Tiantan Hospital Capital Medical University; 🇨🇳 Beijing, Beijing, China

Tianjin Medical University General Hospital; 🇨🇳 Tianjin, Tianjin, China

First Hospital of Shanxi Medical University; 🇨🇳 Taiyuan, Shanxi, China