Efficacy and Safety of Peginterferon Beta-1a (CinnaGen) Versus CinnoVex® (CinnaGen) in Reducing the Annualized Relapse Rate in Participants With Relapsing Remitting Multiple Sclerosis: A Phase III, Randomized, Parallel, Noninferiority Study
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Cinnagen
- 入组人数
- 168
- 试验地点
- 1
- 主要终点
- Annualized Relapse Rate
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of peginterferon beta-1a produced by CinnaGen compared with CinnoVex® (CinnaGen) in subjects with relapsing remitting multiple sclerosis (RRMS). All the participants will receive one of the following regimens: pegylated interferon beta-1a (CinnaGen), autoinjector (Physioject™), 125mcg, subcutaneous, every 2 weeks for 24 months or CinnoVex® (CinnaGen), prefilled syringes, 30mcg, intramuscular, once a week for 24 months. The primary objective of this study is to verify the non-inferiority of peginterferon beta-1a (CinnaGen) versus CinnoVex® (CinnaGen) in reducing the annualized relapse rate (ARR) in participants with relapsing remitting multiple sclerosis (RRMS) at 2 years.
The secondary objectives of this study are:
- Reducing the total number of new or newly enlarging T2 hyperintense lesions on brain magnetic resonance imaging (MRI) scans
- Slowing the progression of disability
- Comparing adverse events
详细描述
The purpose of this phase III, randomized, active control, parallel, non-inferiority, multicenter study is to verify the non-inferiority of peginterferon beta-1a produced by CinnaGen versus CinnoVex® (CinnaGen) in subjects with relapsing remitting multiple sclerosis (RRMS).
All the participants will receive one of the following regimens:
I. Pegylated interferon beta-1a (CinnaGen), autoinjector (Physioject™), 125mcg, subcutaneous, every 2 weeks for 24 months; II. Interferon beta-1a, CinnoVex® (CinnaGen), prefilled syringes, 30mcg, intramuscular, once a week for 24 months.
With the aim of ensuring the compliance and safety, in the first two months of the study, in each monthly visit, a trained expert nurse will be responsible for drug injection for both intervention groups and will train all patients for self-injection. By the end of the first two months to the end of the study, patients will self-inject the medication in both groups.
All other cares or medications will be allowed to continue by patients, except for disease modifying therapies (DMTs) and medicines which affect the immune system (e.g. immunosuppressants and immunomodulators). Any concomitant medication will be recorded for patients in their regular visits.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Relapsing-remitting multiple sclerosis diagnosis (based on McDonald criteria 2010)
- •Expanded Disability Status Scale between 0 to 5
- •At least one relapse having occurred within the past 12 months.
- •Subjects have refused alternative treatments and other available therapies
- •Ability to understand the purpose and risks of the study and provide signed and dated informed consent
- •Negative pregnancy test for women of childbearing age
排除标准
- •Primary progressive, secondary progressive, or progressive relapsing MS
- •Female subjects considering becoming pregnant while in the study or currently breastfeeding
- •Subjects for whom MRI was contraindicated, i.e., who had pacemakers or other contraindicated implanted metal devices, were allergic to gadolinium, or had claustrophobia that could not be medically managed.
- •Unwillingness or inability to comply with the requirements of the protocol including the presence of any condition (physical, mental or social) that was likely to affect the subject's ability to comply with the protocol.
- •Pre-specified laboratory abnormalities
- •History of any clinically significant (as determined by the Investigator) cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, and renal, or other major disease that would preclude participation in a clinical trial.
- •History of malignant disease, including solid tumors and hematologic malignancies (with the exception of basal cell and squamous cell carcinomas of the skin that have been completely excised and are considered cured).
- •History of seizure disorder or unexplained blackouts or history of a seizure within 3 months prior to baseline.
- •History of suicidal ideation within 3 months prior to Baseline or an episode of severe depression within 3 months prior to Baseline. Severe depression is defined as an episode of depression that requires hospitalization, or at the discretion of the Investigator.
- •Abnormal screening blood tests exceeding any of the limits defined below:
- •Alanine transaminase/serum glutamate pyruvate transaminase (ALT/SGPT) greater than 2 times the upper limit of normal (>2 × ULN) or aspartate transaminase/serum glutamic oxaloacetic transaminase (AST/SGOT) >2 × ULN or bilirubin >1.5 × ULN.
- •Total white blood cell count (WBC) <4000 /mm3
- •Absolute Neutrophil Count (ANC) of < 1500 /mm3
- •Platelet count <150,000 c/mm3
- •Hemoglobin <10 g/dL in female subjects; <11 g/dL in male subjects
- •Serum creatinine> upper limit of normal lab value
- •A MS relapse that has occurred within the 30 days prior to randomization and/or the subject has not been stabilized from a previous relapse prior to randomization (Day 1).
- •Elective surgery performed within 2 weeks prior to randomization (Day 1) or scheduled to be performed through the study interval.
- •Treatment with other agents to treat MS symptoms or underlying disease as specified below:
- •Agent Time Required off Agent Prior to Baseline:
- •Any prior treatment with:
- •Total Lymphoid Irradiation
- •Cladribine
- •T-cell Vaccine
- •Natalizumab
- •Rituximab
- •Plegridy®
- •Prior treatment within 1 year of randomization:
- •Cyclophosphamide
- •Mitoxantrone
- •Prior treatment within 6 months prior to randomization:
- •Cyclosporine
- •Plasma exchange
- •Intravenous immunoglobulin (IVIG)
- •Azathioprine
- •Methotrexate
- •Subjects must have discontinued interferon treatment at least 6 months prior to randomization
- •Prior treatment within 30 days prior to randomization:
- •Systemic corticosteroids
- •Prior treatment with glatiramer acetate within 4 weeks prior to randomization
- •Treatment with another investigational drug or approved therapy for investigational use within the 6 months prior to randomization
- •Other unspecified reasons that, in the opinion of the Investigator, made the subject unsuitable for enrolment
研究组 & 干预措施
CinnaGen peginterferon beta-1a
Pegylated interferon beta-1a (CinnaGen) autoinjector (Physioject™),125 mcg, subcutaneous (SC) injection, every 2 weeks, for 24 months
干预措施: Pegylated interferon beta-1a (Drug)
CinnoVex®
Interferon Beta-1A Prefilled Syringe, CinnoVex® (CinnaGen), 30 mcg, intramuscular injection, once a week, for 24 months
干预措施: Interferon Beta-1A Prefilled Syringe (Drug)
结局指标
主要结局
Annualized Relapse Rate
时间窗: 96 weeks
The total number of relapses divided by the total person-time at risk of relapse. A relapse is defined as the appearance of a new or worsening of a previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding relapse. The abnormality must be present for at least 24 hours and occur in the absence of fever or infection.
次要结局
- Total number of gadolinium enhancing lesions as detected by brain MRI(Baseline up to week 96)
- Volume of new or newly enlarging T2 hyperintense lesions as detected by brain MRI(Baseline up to week 96)
- Proportion of patients with 12 weeks of sustained disability progression(Baseline up to week 96)
- Total number of new or newly enlarging T2-hyperintense lesions as detected by brain MRI(Baseline up to week 96)
- Total number of new or newly enlarging T1 hypointense lesions as detected by brain MRI(Baseline up to week 96)
- Volume of gadolinium enhancing lesions as detected by brain MRI(Baseline up to week 96)
- Volume of new or newly enlarging T1 hypointense lesions as detected by brain MRI(Baseline up to week 96)
- Brain atrophy(Baseline up to week 96)
- Total number of new active lesions as detected by brain MRI(Baseline up to week 96)