NMO Spectrum Disorder
Conditions
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.
Interventions
DRUGB001 injection
B001 injection 50mg/5mL Intravenous solution
BIOLOGICALPlacebo
Placebo 5mL Intravenous solution
Sponsors
Shanghai Pharmaceuticals Holding Co., Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
Countries
China
Contacts
CONTACTFu-Dong Shi, MD,PhD
PRINCIPAL_INVESTIGATORFu-Dong Shi, MD,PhD
Tianjin Medical University General Hospital
Outcome results
None listed