A Phase Ⅱ Study to Evaluate the Safety and Efficacy of Mitoxantrone Hydrochloride Liposome Injection for Relapsing Multiple Sclerosis
Overview
- Phase
- Phase 2
- Intervention
- Mitoxantrone Hydrochloride Liposome Injection
- Conditions
- Relapsing Multiple Sclerosis
- Sponsor
- CSPC Zhongnuo Pharmaceutical (Shijiazhuang) Co., Ltd.
- Locations
- 1
- Primary Endpoint
- The cumulative number of new Gadolinium (Gd)-enhancing lesions at the end of 48 weeks of Mitoxantrone Hydrochloride Liposome Injection treatment in brain MRI.
- Status
- Withdrawn
- Last Updated
- 3 years ago
Overview
Brief Summary
This is a multicenter, randomized, single-arm, open-label Phase II study to evaluate the efficacy and safety of Mitoxantrone Hydrochloride Liposome Injection with different doses in participants with Relapsing Multiple Sclerosis. Participants will be randomly enrolled into three treatment groups: Mitoxantrone Hydrochloride Liposome Injection 4 mg/m^2 group, Mitoxantrone Hydrochloride Liposome Injection 8 mg/m^2 group, and Mitoxantrone Hydrochloride Liposome Injection 12 mg/m^2 group. The primary outcome measure is the cumulative number of new Gd-enhancing lesions at the end of 48 weeks of Mitoxantrone Hydrochloride Liposome Injection treatment in brain MRI.
Detailed Description
Multiple sclerosis is a chronic, inflammatory, demyelinating disease of the central nervous system (CNS) and is one of the most common causes of neurological disability in young adults. It is characterised by multi-focal recurrent attacks of neurological symptoms and signs with variable recovery.This is a multicenter, randomized, single-arm, open-label Phase II study to evaluate the efficacy and safety of Mitoxantrone Hydrochloride Liposome Injection with different doses in participants with Relapsing Multiple Sclerosis. Participants will be randomly enrolled into three treatment groups: Mitoxantrone Hydrochloride Liposome Injection 4 mg/m\^2 group, Mitoxantrone Hydrochloride Liposome Injection 8 mg/m\^2 group, and Mitoxantrone Hydrochloride Liposome Injection 12 mg/m\^2 group. The primary outcome measure is the cumulative number of new Gd-enhancing lesions at the end of 48 weeks of Mitoxantrone Hydrochloride Liposome Injection treatment in brain MRI.
Investigators
Eligibility Criteria
Inclusion Criteria
- •18 to 55 years of age (inclusive);
- •Diagnosis of relapsing multiple sclerosis (RMS);
- •Disease duration of secondary progressive multiple sclerosis (SPMS) with superimposed relapses ≤ 5 years;
- •Expanded disability status scale (EDSS) score of 3 to 8;
- •Participants who have received disease-modifying therapy still relapse or aggravate; or participants who, in the opinion of the investigator, are suitable for treatment with Mitoxantrone Hydrochloride Liposome Injection;
- •Participants voluntarily sign informed consent, and complete the study according to the protocol.
Exclusion Criteria
- •Pregnant or lactating female participants or participants planning to have a child during the study;
- •History of severe drug allergy, or allergy or intolerance to gadolinium, anthracyclines or liposome drugs;
- •History of vitamin B12 deficiency;
- •Participants with malignant tumor diagnosed within 5 years before the screening phase, except the skin basal cell carcinoma under effective control, and Stage I Squamous Cell Carcinoma);
- •Participants with history of interstitial lung disease or with pneumonia according to chest X-ray in the screening phase;
- •Participants with serious or active skin diseases, or clinically significant skin abnormalities in physical examination in the screening phase;
- •History of severe immunodeficiency;
- •History of drug and/or alcohol abuse, or mental disorder;
- •Participants has a progressive neurological disorder or optic neuritis other than MS; or has other disease that should be treated more preferentially than MS, or that could interfere with the study or compromise participants compliance with treatment;
- •MRI before randomization shows cervical spinal cord compression or lesions in non-MS characteristic areas of the brain, and the lesions can explain the changes in clinical symptoms and signs;
Arms & Interventions
Mitoxantrone Hydrochloride Liposome Injection 4 mg/m^2 group
Participants will receive Mitoxantrone Hydrochloride Liposome Injection 4 mg/m\^2 every 3 months (Q3M).
Intervention: Mitoxantrone Hydrochloride Liposome Injection
Mitoxantrone Hydrochloride Liposome Injection 8 mg/m^2 group
Participants will receive Mitoxantrone Hydrochloride Liposome Injection 8 mg/m\^2 every 3 months (Q3M).
Intervention: Mitoxantrone Hydrochloride Liposome Injection
Mitoxantrone Hydrochloride Liposome Injection 12 mg/m^2 group
Participants will receive Mitoxantrone Hydrochloride Liposome Injection 12 mg/m\^2 every 3 months (Q3M).
Intervention: Mitoxantrone Hydrochloride Liposome Injection
Outcomes
Primary Outcomes
The cumulative number of new Gadolinium (Gd)-enhancing lesions at the end of 48 weeks of Mitoxantrone Hydrochloride Liposome Injection treatment in brain MRI.
Time Frame: Week 48
Secondary Outcomes
- Number of new or enlarged T2 lesions.(Week 48)
- Descriptive analysis of the rate of change in the number or proportion of B cells from baseline to different time points in different dose groups.(Week 36)
- Descriptive analysis of the rate of change in the number or proportion of NK cells from baseline to different time points in different dose groups.(Week 36)
- Proportion of participants with ≥ 20% improvement from baseline in T25FW walking speed.(Week 48)
- Change from baseline to Week 48 in T25FW walking speed.(Week 48)
- Number of participants with treatment-related adverse events as assessed by CTCAE v5.0(Week 56)
- Descriptive analysis of the rate of change in the number or proportion of T cells from baseline to different time points in different dose groups.(Week 36)
- Time to Onset of Confirmed Disability Progression for at least 3 Months(Week 48)
- Change from baseline in brain MRI Gd-enhancing T1 lesion volume at Weeks 12、24、36、48.(Week 12、24、36、48)
- Change from baseline in brain MRI T2 lesion volume at Weeks 12、24、36、48.(Week 12、24、36、48)
- Plasma concentration of Mitoxantrone Hydrochloride Liposome Injection.(Week 12)
- Annualized Relapse Rate (ARR)(Week 48)
- Number of Relapses(Week 48)
- Time to Onset of Confirmed Disability Progression for at least 6 Months(Week 48)