Clinical trial NCT05145361: Clinical Study of B001 Injection in Subjects With Neuromyelitis Optic Spectrum Disorder (NMOSD)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: NMO Spectrum Disorder
Lead sponsor: Shanghai Pharmaceuticals Holding Co., Ltd
Sponsor class: INDUSTRY
First posted: 2021-12-06
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Dose-limiting toxicity (DLT)
timeFrame: Up to 18 days.
measure: Evaluate incidence of treatment-emergent adverse events [Safety and Tolerability].
timeFrame: Up to 1 year
Secondary outcomes:
measure: Maximum serum concentration (Cmax) of B001.
timeFrame: Through study completion, up to 2 years
measure: Time of maximum serum concentration (Tmax) of B001.
timeFrame: Through study completion, up to 2 years
measure: Area under the serum concentration-time curve (AUC) of the Dosing Interval (0-14D) of B001.
timeFrame: Through study completion, up to 2 years
measure: Area under the serum concentration-time curve (AUC) of the Dosing Interval (0-Last) of B001.
timeFrame: Through study completion, up to 2 years
measure: Area under the serum concentration-time curve (AUC) of the Dosing Interval (0-infinity) of B001.
timeFrame: Through study completion, up to 2 years
measure: Accumulation ratio of maximum serum concentration (Rac_Cmax) of B001.
timeFrame: Through study completion, up to 2 years
measure: Accumulation ratio of area under the serum concentration-time curve (Rac_AUC) of the Dosing Interval (0-14D) of B001.
timeFrame: Through study completion, up to 2 years
measure: Terminal rate constant(λz) of B001.
timeFrame: Through study completion, up to 2 years
measure: Half-life (t1/2) of B001.
timeFrame: Through study completion, up to 2 years
measure: Total clearance(CL) of B001.
timeFrame: Through study completion, up to 2 years
measure: Volume of distribution(Vz) of B001.
timeFrame: Through study completion, up to 2 years
measure: Percentage of area under the serum concentration-time curve (AUC 0-infinity) obtained by extrapolation (%AUCex) of B001.
timeFrame: Through study completion, up to 2 years
measure: Percentage of subjects with ADA to B001 and neutralizing resistance (Nab)
timeFrame: Through study completion, up to 2 years
measure: Time to First Protocol-Defined Relapse (TFR) in the Double-Blind Period
timeFrame: Through study completion, up to 2 years
measure: Change in Expanded Disability Status Scale (EDSS) Score
timeFrame: Through study completion, up to 2 years
measure: Time to EDSS Worsening
timeFrame: Through study completion, up to 2 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Tiantan Hospital Capital Medical University
state: Beijing
city: Taiyuan
country: China
facility: First Hospital of Shanxi Medical University
state: Shanxi
city: Xi'an
country: China
facility: Tangdu hospital,fourth military medical university
state: Shanxi
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
state: Tianjin
Study officials:
affiliation: Tianjin Medical University General Hospital
name: Fu-Dong Shi, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: