Efficacy and Safety of Mitoxantrone Hydrochloride Liposome Injection in the Treatment of Neuromyelitis Optica Spectrum Disorder (NMOSD)

A Randomized, Double-blind, Placebo-controlled Phase Ⅱ Clinical Study to Evaluate the Efficacy and Safety of Mitoxantrone Hydrochloride Liposome Injection in the Treatment of Neuromyelitis Optica Spectrum Disorder (NMOSD)

This is a multicenter, randomized, double-blind, placebo-controlled Phase Ⅱ study to evaluate the efficacy and safety of Mitoxantrone Hydrochloride Liposome Injection with different doses in participants with neuromyelitis optica spectrum disorder (NMOSD). Participants will be randomly enrolled into three groups: Mitoxantrone Hydrochloride Liposome Injection 8 mg/m^2 group, Mitoxantrone Hydrochloride Liposome Injection 12 mg/m^2 group, and Placebo group. The primary outcome measure is time to first protocol-defined relapse.

Study Overview

• Status: Not yet recruiting
• Conditions: Neuromyelitis Optica Spectrum Disorder
• Intervention / Treatment: Drug: Mitoxantrone Hydrochloride Liposome Injection

• Study Type: Interventional
• Enrollment (Anticipated): 45
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jiaqi Liu; Phone Number: +86-15600050094; Email: liujiaqi01@mail.ecspc.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 18-60 years (inclusive) at the time of signing the informed consent form, both men and women;
2. Participants meet the 2015 international consensus diagnostic criteria for neuromyelitis optica spectrum disease (NMOSD) and are AQP4-IgG positive or negative (acceptable test results within 24 weeks before signing the informed consent form);
3. Experienced at least 2 attacks within 1 year before screening and/or at least 3 relapses in the past 24 months, but have at least 1 documented clinical evidence of attack or relapse (including the first attack) within 12 months before screening;
4. Expanded disability status scale (EDSS) ≤ 7.5 points at screening and baseline retest;
5. Participants voluntarily sign the informed consent form and voluntarily complete the trial according to the protocol requirements.

Exclusion Criteria:

1. Pregnant or lactating female participants, or participants planning to have a child during the study;
2. Any surgical procedure within 4 weeks before randomization, with evidence of other demyelinating diseases or progressive multifocal leukoencephalopathy (PML);
3. Known active infection (excluding nail bed fungal infection or dental caries) within 4 weeks before randomization;
4. Hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCVAb), syphilis antibody, or human immunodeficiency virus (HIV antibody) is positive;
5. History of drug or alcohol abuse or mental disorder within 1 year before randomization;
6. Evidence of active tuberculosis (TB; excluding patients receiving drugs to prevent latent TB infection);
7. Evidence of active interstitial lung disease;
8. Receipt of any live or live attenuated vaccine within 6 weeks before randomization;
9. History of malignancy, including solid tumors, hematological malignancies, and carcinoma in situ (except completely resected and cured basal cell carcinoma and squamous cell carcinoma or cervical carcinoma in situ) within the past 5 years;
10. History of severe drug allergy, allergy or intolerance to Mitoxantrone and liposomes (shock, allergic reactions);
11. Participants with other chronic active immune system diseases other than NMOSD or stable disease but requiring high-dose glucocorticoid maintenance therapy: such as rheumatoid arthritis, scleroderma, Schogren' s syndrome, ulcerative colitis, genetic immunodeficiency or drug-induced immunodeficiency; participants with positive autoantibodies only but without clinical manifestations can be enrolled in the trial;
12. Participants with other diseases not suitable for this study as judged by the investigator;
13. Received any investigational agent within 3 months prior to randomization, or participated in a medical device clinical study and judged by the investigator to have a potential impact on the results of this trial;
14. History of prior NMOSD therapy with any of the following: a. received prior mitoxantrone or anthracycline therapy, total body irradiation, or bone marrow transplantation at any time; b. received rituximab or any experimental B-cell depleting agent within 6 months prior to randomization, unless the participant had a B-cell count higher than LLN in the central laboratory; c. used any of the following within 3 months prior to randomization: Satralizumab,Tocilizumab,inebilizumab,Eculizumab,Alemtuzumab,Ciclosporin,Azathioprine,Cyclophosphamide,Tacrolimus,Mycophenolate mofetil. Any other treatment to prevent relapses in multiple sclerosis (MS) (eg, Interferon, Natalizumab, Glatiramer acetate, Fingolimod, Teriflunomide, or Dimethyl fumarate); d. intravenous immunoglobulin (IVIG) therapy, plasma exchange therapy (PE) within 1 month prior to randomization; e. participants who are receiving oral corticosteroids at doses higher than 30 mg/day in prednisolone conversion; f. anti-CD4, cladribine within 2 years prior to randomization.
15. Presence of the following clinically significant diseases: a. cardiac ejection fraction (EF) less than 50% by echocardiography or lower than the lower limit of laboratory values at the study site; history of chronic congestive heart failure, cardiac function NYHA class Ш ~ Ⅳ; b. any of the following events within 3 months before randomization: myocardial infarction, acute coronary syndrome, viral myocarditis, pulmonary embolism, stroke; coronary revascularization within 6 months; c. screening ECG showed QTc interval > 480 ms (according to Fridericia correction formula, QTc = QT/RR^0.33), or a history of severe QTc prolongation.
16. Patients with the following abnormalities in laboratory values during screening: a. aspartate aminotransferase (AST) > 3 × upper limit of normal (ULN), alanine aminotransferase (ALT) > 3 × ULN, total bilirubin > 1.5 × ULN (unless due to Gilbert 's syndrome); b. platelet count < 50,000/μL (or < 50 × 10^9/L), hemoglobin < 9 g/dL (or < 90 g/L), white blood cells < 2.0 × 10^3/μL, absolute neutrophil count < 1.0 × 10^3/μL; c. creatinine clearance (CLcr) < 60 mL/min (calculated using the Cockcroft-Gault formula: [140 - age (years)] × [body weight (kg)] × (0.85, if female)/[72 × serum creatinine (mg/dL)]) or receiving dialysis during screening;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Mitoxantrone Hydrochloride Liposome Injection 8 mg/m^2 group	Drug: Mitoxantrone Hydrochloride Liposome Injection; IV, once every 12 weeks (Q12W)
EXPERIMENTAL: Mitoxantrone Hydrochloride Liposome Injection 12 mg/m^2 group	Drug: Mitoxantrone Hydrochloride Liposome Injection; IV, once every 12 weeks (Q12W)
PLACEBO_COMPARATOR: Placebo Injection every 12 weeks (Q12W).	Drug: Mitoxantrone Hydrochloride Liposome Injection; IV, once every 12 weeks (Q12W)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First Protocol-defined Relapse	Time to First Protocol-defined Relapse was defined as time from randomization to first occurrence of relapse. Protocol-defined relapse was occurrence of new or worsening neurological symptoms attributable to neuromyelitis optica spectrum disorder (NMOSD).	Up to Week 48

Collaborators and Investigators

• Sponsor: CSPC Zhongnuo Pharmaceutical (Shijiazhuang) Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): November 15, 2022
• Primary Completion (ANTICIPATED): October 15, 2024
• Study Completion (ANTICIPATED): April 15, 2025

Study Registration Dates

• First Submitted: September 20, 2022
• First Submitted That Met QC Criteria: September 20, 2022
• First Posted (ACTUAL): September 22, 2022

Study Record Updates

• Last Update Posted (ACTUAL): September 22, 2022
• Last Update Submitted That Met QC Criteria: September 20, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Eye Diseases; Optic Nerve Diseases; Cranial Nerve Diseases; Myelitis, Transverse; Optic Neuritis; Neuromyelitis Optica; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Mitoxantrone
• Other Study ID Numbers: HE071-CSP-028

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No