Clinical Study of B001 Injection in Subjects With Neuromyelitis Optic Spectrum Disorder (NMOSD)
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Early Phase 1 |
Study Design
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- Dose-limiting toxicity (DLT) [Up to 18 days.]
Measurement of DLT in all subjects.
- Maximum tolerated dose (MTD) [Up to 18 days.]
Measurement of MTD in all subjects.
- Evaluate incidence of treatment-emergent adverse events [Safety and Tolerability]. [Up to 1 year]
Secondary Outcome Measures
- Maximum serum concentration (Cmax) of B001. [Through study completion, up to 2 years]
To characterize the PK (Pharmacokinetics) of B001.
- Time of maximum serum concentration (Tmax) 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 maximum serum concentration (Rac_Cmax) 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.
- 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.
- Total clearance(CL) 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 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.
- 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 [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 EDSS Worsening [Through study completion, up to 2 years]
Eligibility Criteria
Criteria
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) <2.0 x10^3/μL
-
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Beijing Tiantan Hospital Capital Medical University | Beijing | Beijing | China | 100050 |
| 2 | First Hospital of Shanxi Medical University | Taiyuan | Shanxi | China | 030001 |
| 3 | Tianjin Medical University General Hospital | Tianjin | Tianjin | China | 300052 |
Sponsors and Collaborators
- Shanghai Pharmaceuticals Holding Co., Ltd
Investigators
- Principal Investigator: Fu-Dong Shi, MD,PhD, Tianjin Medical University General Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- B001-103