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)

Shanghai Pharmaceuticals Holding Co., Ltd4 sites in 1 country45 target enrollmentApril 7, 2022

ConditionsNMO Spectrum Disorder

InterventionsB001 injection Placebo

Overview

Phase: Early Phase 1
Intervention: B001 injection
Conditions: NMO Spectrum Disorder
Sponsor: Shanghai Pharmaceuticals Holding Co., Ltd
Enrollment: 45
Locations: 4
Primary Endpoint: Dose-limiting toxicity (DLT)
Status: Recruiting
Last Updated: 8 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

April 7, 2022

End Date

December 15, 2025

Last Updated

8 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Shanghai Pharmaceuticals Holding Co., Ltd

Responsible Party

Sponsor

Eligibility 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)

Arms & Interventions

B001 injection

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

Intervention: B001 injection

Placebo

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

Intervention: Placebo

Outcomes

Primary Outcomes

Dose-limiting toxicity (DLT)

Time Frame: Up to 18 days.

Measurement of DLT in all subjects.

Evaluate incidence of treatment-emergent adverse events [Safety and Tolerability].

Time Frame: Up to 1 year

Secondary Outcomes

Time of maximum serum concentration (Tmax) of B001.(Through study completion, up to 2 years)
Maximum serum concentration (Cmax) of B001.(Through study completion, up to 2 years)
Terminal rate constant(λz) of B001.(Through study completion, up to 2 years)
Half-life (t1/2) 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.(Through study completion, up to 2 years)
Change in Expanded Disability Status Scale (EDSS) Score(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)
Area under the serum concentration-time curve (AUC) of the Dosing Interval (0-14D) of B001.(Through study completion, up to 2 years)
Accumulation ratio of maximum serum concentration (Rac_Cmax) 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.(Through study completion, up to 2 years)
Area under the serum concentration-time curve (AUC) of the Dosing Interval (0-infinity) 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.(Through study completion, up to 2 years)
Volume of distribution(Vz) 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)
Total clearance(CL) of B001.(Through study completion, up to 2 years)
Time to EDSS Worsening(Through study completion, up to 2 years)