A multi-centre, open label, single arm phase IV study to assess the safety and effectiveness of Ocrelizumab in multiple sclerosis (RMS And PPMS) patients in India (Overture)
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 32
- 试验地点
- 6
- 主要终点
- 1.To describe the safety of ocrelizumab in RMS and PPMS patients (separate and pooled analysis) over a period of approximately 96 weeks
研究概览
简要总结
Study ML45008 is a Phase IV study to evaluate the safety and effectiveness of ocrelizumab in adult patients with RMS and PPMS. All eligible patients will receive 600 mg intravenously ocrelizumab. Approximately 32 patients will be enrolled (in which minimum 10% patients with PPMS will be enrolled) by approximately 10 Indian sites. Patients who discontinue study medication early or discontinue from the study will not be replaced.
This study will follow study patients for up to 24 weeks after the last dose to determine safety and effectiveness of ocrelizumab therapy. The effectiveness of ocrelizumab therapy will be based on clinical assessments as well as various MS-related clinical and radiological outcomes.
All patients will be treated with ocrelizumab. Patient’s participation in the study will consists of three periods: screening period of 28 days, treatment period of 72 weeks, and post-treatment follow-up period of 24 weeks. The eligibility of the patients will be assessed within 28 days of the screening period. The estimated duration of patient enrollment is approximately 12 months.
During the study treatment period, RMS and PPMS patients will receive ocrelizumab as per the label. The initial 600 mg dose is administered as two separate intravenous (IV) infusions; first as a 300 mg infusion, followed 2 weeks later by a second 300 mg infusion. Subsequent doses of ocrelizumab thereafter are administered as a single 600 mg IV infusion every 6 months. Pre-medication is administered as per the local prescribing information and according to the physician’s judgment.
Patients will be assessed for effectiveness of ocrelizumab treatment on relapse in RMS patients via number of relapses; annualized relapse rate, and time to first relapse. Patients will be assessed for effectiveness of ocrelizumab treatment on progression of disability in RMS and PPMS patients by assessing the change in T25FWT.
In addition, subclinical disease activity will be assessed through imaging endpoints in RMS and PPMS, separate and pooled analysis by assessing total number of T1 gadolinium enhancing (T1Gd+) lesions from the baseline and new/enlarging T2-weighted lesions as detected by magnetic resonance imaging (MRI) scan.
研究设计
- 研究类型
- Interventional
- 分配方式
- Not Applicable
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 55.00 Year(s)（—）
- 性别
- All
入选标准
- •1.Age 18 to 55 years 2.For RMS: A diagnosis of RMS in accordance with the revised 2017 McDonald Criteria (Thompson et al.
- •and one of the following: At least two documented clinical relapses within the last 1.5 years or one documented clinical relapse within 12 months of screening (but not within the 30 days prior to screening) Documented evidence of the presence of at least one T1Gd+ lesion on MRI in the 12 months prior to screening RMS may include active secondary progressive multiple sclerosis (aSPMS) as defined by Lublin et al.
- •For PPMS-Progressive disease from the onset One year of disability progression (retrospectively or prospectively determined) independent of clinical relapse Plus two of the following criteria: Documented evidence of one or more T2-hyperintense MRI lesions characteristic of MS in one or more of the following brain regions: periventricular, cortical or juxtacortical, or infratentorial Documented evidence of two or more T2-hyperintense MRI lesions in the spinal cord Documented evidence of the presence of cerebrospinal fluid-specific oligoclonal bands (established by a historical lumbar puncture) This will be confirmed centrally by an independent neurologist.
- •3.No prior exposure to long-term immunomodulatory medication, however, appropriate washout period may be allowed for few immunomodulatory medications 4.Ability to provide informed consent 5.For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use adequate non-hormonal contraception during the treatment period and for 6 months’ time needed to eliminate drug after the final dose of ocrelizumab.
排除标准
- •1.Any known or suspected active infection at screening or baseline, or any major episode of infection requiring hospitalization or treatment with IV anti microbials within 8 weeks prior to and during screening or treatment with oral anti microbials within 2 weeks prior to and during screening 2.History of confirmed or suspected progressive multifocal leukoencephalopathy (PML) 3.Patients with a previous history of a serious infusion-related reactions (IRR) (Common Terminology Criteria for Adverse Events [CTCAE] Grade more than or equal to 4) and/or any hypersensitivity reaction to ocrelizumab 4.History of cancer, including hematologic malignancy and solid tumors, within 10 years of screening Basal or squamous cell carcinoma of the skin that has been excised and is considered cured is not exclusionary.
- •In situ carcinoma of the cervix treated with apparent success by curative therapy > 1 year prior to screening is not exclusionary.
- •5.Immunocompromised state, defined as one or more of the following: CD4 count less than 250/mL or absolute neutrophil count 1.5x10 raise-to 3 /mL or serum IgG less than 500 mg/dL 6.Known presence of other significant neurological disorders 7.Evidence of clinically significant systemic/organ disorders that, in the investigators opinion, would preclude patient participation 8.Screening 12 lead electrocardiogram (ECG) that demonstrates clinically relevant abnormalities that may affect patient safety or interpretation of study results including QT interval corrected through use of Fridericias formula (QTcF) more than 440 ms demonstrated by at least two ECGs more than 30 minutes apart 9.Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study 10.Pregnant or breastfeeding, or intending to become pregnant during the study or 6 or 12 months (as applicable from the local label for ocrelizumab) after final dose of study drug 11.All women of childbearing potential will have a serum pregnancy test at screening.
- •12.Positive screening tests for active, latent, or inadequately treated hepatitis B (as evidenced by either of the following): Positive hepatitis B surface antigen Positive hepatitis B core antibody [total HBcAb] and detectable Hep B virus DNA 13.Positive screening tests for hepatitis C (positive hepatitis C antibodies) 14.Evidence of active or latent or inadequately treated infection with tuberculosis (TB) as defined by the following: A positive QuantiFERON TB Gold (QFT) test at screening or within the 3 months prior to screening is required (see Section 8.2.5 for test requirements).
- •An indeterminate QFT test should be repeated.
- •A positive QFT test or two successive indeterminate QFT results should be considered a positive diagnostic TB test.
- •An indeterminate QFT test followed by a negative QFT test should be considered a negative diagnostic TB test.
- •15.History of or currently active primary or secondary (non-drug related) immunodeficiency, including known history of HIV infection or IgG less than 500 mg/dL 16.Contraindications to mandatory pre-medications (i.e., corticosteroids and antihistamines) for IRRs, including: Uncontrolled psychosis for corticosteroids Closed angle glaucoma for antihistamines 17.Inability to complete an MRI scan (contraindications for MRI scan, including but not restricted to, pacemaker, cochlear implants, intracranial vascular clips, surgery within 6 weeks of entry in the study, coronary stent implanted within 8 weeks prior to the time of the intended MRI scan) or contraindication to gadolinium administration 18.Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants 19.Receipt of a live or live attenuated vaccine within 6 weeks prior to dosing.
- •Influenza vaccination is permitted if the inactivated vaccine formulation is administered.
- •20.Treatment with any investigational agent within 24 weeks prior to screening or 5 half lives of the investigational drug (whichever is longer), or treatment with any experimental procedure for MS 21.Any abnormal laboratory findings that can interfere with ocrelizumab dosing as judged by the investigator to be clinically significant.
结局指标
主要结局
1.To describe the safety of ocrelizumab in RMS and PPMS patients (separate and pooled analysis) over a period of approximately 96 weeks
时间窗: 1. Incidence & time and reason of ocrelizumab discontinuation from Day 1 to Week 96 | 2. Number of relapses in RMS patients from Day 1 to | Week 96. | 3. Annualized relapse rate, defined as number of | relapses per patient-year | 4. Time to first relapse | 5. The change in T25FWT from Day 1 to Week 96
2. To describe the time to treatment discontinuation with ocrelizumab and reasons for treatment discontinuation
时间窗: 1. Incidence & time and reason of ocrelizumab discontinuation from Day 1 to Week 96 | 2. Number of relapses in RMS patients from Day 1 to | Week 96. | 3. Annualized relapse rate, defined as number of | relapses per patient-year | 4. Time to first relapse | 5. The change in T25FWT from Day 1 to Week 96
3. To describe the effectiveness of ocrelizumab treatment on relapse in RMS patients.
时间窗: 1. Incidence & time and reason of ocrelizumab discontinuation from Day 1 to Week 96 | 2. Number of relapses in RMS patients from Day 1 to | Week 96. | 3. Annualized relapse rate, defined as number of | relapses per patient-year | 4. Time to first relapse | 5. The change in T25FWT from Day 1 to Week 96
4. To describe the effectiveness of ocrelizumab treatment on progression of disability in RMS and PPMS patients
时间窗: 1. Incidence & time and reason of ocrelizumab discontinuation from Day 1 to Week 96 | 2. Number of relapses in RMS patients from Day 1 to | Week 96. | 3. Annualized relapse rate, defined as number of | relapses per patient-year | 4. Time to first relapse | 5. The change in T25FWT from Day 1 to Week 96
次要结局
- To describe the effectiveness of(ocrelizumab on subclinical)