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

NMO Spectrum Disorder Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05145361
• Other study ID #: B001-103
• Status: Recruiting
• Phase: Early Phase 1
• Start date: April 7, 2022
• Est. completion date: December 15, 2024

Study information

• Verified date: May 2023
• Source: Shanghai Pharmaceuticals Holding Co., Ltd
• Contact: Fu-Dong Shi, MD,PhD
• Phone: 022-60814587
• Email: Shifudong219[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: December 15, 2024
• Est. primary completion date: December 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Neuromyelitis Optica
• NMO Spectrum Disorder

Intervention

Drug:
• B001 injection
B001 injection 50mg/5mL Intravenous solution

Biological:
• Placebo
Placebo 5mL Intravenous solution

Locations

Country	Name	City	State
China	Beijing Tiantan Hospital Capital Medical University	Beijing	Beijing
China	First Hospital of Shanxi Medical University	Taiyuan	Shanxi
China	Tianjin Medical University General Hospital	Tianjin	Tianjin
China	Tangdu hospital,fourth military medical university	Xi'an	Shanxi

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Pharmaceuticals Holding Co., Ltd

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicity (DLT)	Measurement of DLT in all subjects.	Up to 18 days.
Primary	Evaluate incidence of treatment-emergent adverse events [Safety and Tolerability].		Up to 1 year
Secondary	Maximum serum concentration (Cmax) of B001.	To characterize the PK (Pharmacokinetics) of B001.	Through study completion, up to 2 years
Secondary	Time of maximum serum concentration (Tmax) of B001.	To characterize the PK (Pharmacokinetics) of B001.	Through study completion, up to 2 years
Secondary	Area under the serum concentration-time curve (AUC) of the Dosing Interval (0-14D) of B001.	To characterize the PK (Pharmacokinetics) of B001.	Through study completion, up to 2 years
Secondary	Area under the serum concentration-time curve (AUC) of the Dosing Interval (0-Last) of B001.	To characterize the PK (Pharmacokinetics) of B001.	Through study completion, up to 2 years
Secondary	Area under the serum concentration-time curve (AUC) of the Dosing Interval (0-infinity) of B001.	To characterize the PK (Pharmacokinetics) of B001.	Through study completion, up to 2 years
Secondary	Accumulation ratio of maximum serum concentration (Rac_Cmax) of B001.	To characterize the PK (Pharmacokinetics) of B001.	Through study completion, up to 2 years
Secondary	Accumulation ratio of area under the serum concentration-time curve (Rac_AUC) of the Dosing Interval (0-14D) of B001.	To characterize the PK (Pharmacokinetics) of B001.	Through study completion, up to 2 years
Secondary	Terminal rate constant(?z) of B001.	To characterize the PK (Pharmacokinetics) of B001.	Through study completion, up to 2 years
Secondary	Half-life (t1/2) of B001.	To characterize the PK (Pharmacokinetics) of B001.	Through study completion, up to 2 years
Secondary	Total clearance(CL) of B001.	To characterize the PK (Pharmacokinetics) of B001.	Through study completion, up to 2 years
Secondary	Volume of distribution(Vz) of B001.	To characterize the PK (Pharmacokinetics) of B001.	Through study completion, up to 2 years
Secondary	Percentage of area under the serum concentration-time curve (AUC 0-infinity) obtained by extrapolation (%AUCex) of B001.	To characterize the PK (Pharmacokinetics) of B001.	Through study completion, up to 2 years
Secondary	Percentage of subjects with ADA to B001 and neutralizing resistance (Nab)		Through study completion, up to 2 years
Secondary	Time to First Protocol-Defined Relapse (TFR) in the Double-Blind Period		Through study completion, up to 2 years
Secondary	Change in Expanded Disability Status Scale (EDSS) Score	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.	Through study completion, up to 2 years
Secondary	Time to EDSS Worsening		Through study completion, up to 2 years