A Single-arm, Prospective, Multi-center Study to Explore Maintained Efficacy With Ofatumumab Therapy in Patients With Relapsing Multiple Sclerosis Who Discontinue Intravenously Delivered Anti-CD20 Monoclonal Antibody (aCD20 mAb) Therapy (OLIKOS)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 111
- 试验地点
- 39
- 主要终点
- Percentage of Participants With no Change or a Reduction From Baseline in the Number of Gadolinium Enhancing (GdE) Lesions at Month 12 Using Non-responder Imputation
研究概览
简要总结
A single arm study evaluating the continued efficacy, safety and tolerability of ofatumumab in patients with relapsing multiple sclerosis who are transitioning from aCD20 mAb therapy
详细描述
This was a single-arm, multicenter, prospective, study in participants with relapsing multiple sclerosis (MS) who had been previously treated with intravenous (i.v.) anti-CD20 monoclonal antibody (aCD20 mAb) therapy and had received at least 2 consecutive courses of intravenously administered ocrelizumab or rituximab every 6 months, and the last dose was within 4 to 9 months before Baseline/Day 1. In this study, participants could have enrolled only if discontinuing i.v. aCD20 mAb therapy for reasons other than lack of efficacy or due to certain treatment-emergent adverse events (TEAEs). Reasons for switching could have included but were not limited to physician/participant preference, access to commercial drug (e.g. insurance coverage issues), or for other logistical reasons (e.g. geographical relocation, travel, etc.).
Eligible participants received open label ofatumumab 20 mg subcutaneous (s.c.) once monthly for 12 months following initial loading regimen of 20 mg s.c. doses on Days 1, 7, and 14. After the 12-Month Treatment Period there was a Telephone Safety Follow-up call 30 days after last dose of study treatment. The Core phase covered a 28-day Screening Period, 12-Month Treatment Period, and 30-Day Telephone Safety Follow-up.
Upon completing the study, participants could opt to continue ofatumumab therapy through commercial services. Participants who did not continue into the ofatumumab commercial patient services hub within 1 month of the end of study visit or who did not switch to another therapy had to continue into the Post-Treatment Safety Follow-up period, consisting of every 3 month visits including B cell monitoring, until they were able to start on commercial ofatumumab, until they switched to another therapy, or until their B cells were repleted (defined as a B cell concentration greater than the individual participant's baseline value prior to starting the i.v. aCD20 mAb or greater than the lower limit of normal).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants eligible for inclusion in this study must meet all of the following criteria:
- •Written informed consent must be obtained before any assessment is performed.
- •Male or female participants aged 18 to 60 years (inclusive) at screening.
- •Diagnosis of relapsing MS (RMS) according to the 2017 Revised McDonald criteria (Thompson et al. 2018), including CIS, RRMS or SPMS with disease activity as defined by (Lublin et al. 2014).
- •Disability status at Screening with an EDSS score of 0 to 5.5 (inclusive).
- •Received at least 2 courses of intravenous aCD20 mAb (loading doses are considered 1 course):
- •Participants currently treated with ocrelizumab must have received (meet all three criteria below):
- •1. 2 fully infused initial 300 mg ocrelizumab iv infusions
- •At least 1 fully infused 600 mg ocrelizumab iv infusions 6 months (+/- one month)
- •Last fully infused ocrelizumab dose must have occurred within 4-9 months prior to baseline
- •Participants currently treated with rituximab must have received (meet both criteria below):
- •At least 2 fully infused courses of rituximab 500 mg - 1000 mg iv every 6 months (+/- one month).
- •Initial loading regimens of rituximab i.e. 500 mg - 1000 mg on day 1 and on day 15, are allowed but this is consider a single course and must be followed by additional infusion(s) every 6 months (+/- one month)
- •Last fully infused rituximab dose must have occurred within 4-9 months prior to baseline.
- •6. Participants discontinuing aCD20 therapy for reasons including, but not limited to: physician/participant preference, access to commercial drug (e.g. insurance coverage issues) or for other logistical reasons (such as geographical relocation, travel, etc.) are eligible for this study.
- •Neurologically stable within 1 month prior to first study drug administration.
- •8. Must be able to use a smart device or have a caregiver that can assist.
排除标准
- •Participants meeting any of the following criteria are not eligible for inclusion in this study:
- •Participants that have demonstrated suboptimal response to aCD20 therapy to include:
- •a. Signs of MRI activity, defined as ≥ 2 active Gd+ T1 lesions, or any new or newly enlarging T2 lesions, documented within the past 6 months
- •If a prior MRI within the last 6 months is not available, then new or newly enlarging T2 lesions should be considered "not documented" and the patient may continue screening b. Documented relapse while on stable, previous aCD20 treatment.
- •Relapses during the first 3 months of intravenous aCD20 therapy are allowable if the participant is then relapse-free for the 12 months following the relapse while on intravenous aCD20 therapy c. Any signs of clinical worsening as measured by EDSS or any clinical measure documented within the last 6 months
- •Discontinuing aCD20 mAb therapy due to the following treatment- emergent adverse events:
- •Severe infusion-related reactions (Grade 3 or above)
- •Recurrent infections defined as ≥ 2 severe infections or ≥ 3 respiratory infections or the need for ≥ 2 courses of antibiotics since starting aCD20 therapy, if the Investigator believes this is related to therapy.
- •Decreased IgG requiring treatment with Intravenous immunoglobulin
- •Participants with primary progressive MS (Polman et al 2011) or SPMS without disease activity (Lublin et al 2014).
- •Participants meeting criteria for neuromyelitis optica (Wingerchuk et al 2015).
- •Pregnant or nursing (lactating) women
- •Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for at least 6 months after stopping study medication.
- •Participants with active chronic disease (or stable but treated with immune therapy) of the immune system other than MS (e.g. rheumatoid arthritis, scleroderma, Sjögren's syndrome, Crohn's disease, ulcerative colitis, etc.) or with immunodeficiency syndrome (hereditary immune deficiency, drug-induced immune deficiency).
- •Participants with active systemic bacterial, viral or fungal infections, or known to have acquired immunodeficiency syndrome (AIDS).
- •Participants with neurological symptoms consistent with PML or with confirmed PML.
- •Participants at risk of developing or having reactivation of syphilis or tuberculosis
- •Participants at risk of developing or having reactivation of hepatitis.
- •Have received any live or live-attenuated vaccines (including for varicella-zoster virus or measles) within 4 weeks prior to first study drug administration. a. There is presently no contraindication for the use of an inactivated, viral-vector-or mRNA based Sars-CoV-2 vaccine in patients who are immunocompromised. However, different Sars-CoV-2 vaccines may have various mechanisms of action and different associated potential risks. Please review local prescribing information of any specific Sars-CoV-2 vaccine and comply with local prescribing information requirements for specific contra-indications and special warnings and precautions for use.
研究组 & 干预措施
Ofatumumab
Investigational drug will be provided in an autoinjector for subcutaneous administration containing 20 mg ofatumumab (20 mg/0.4 ml) administered at baseline, Day 7, Day 14 and monthly thereafter
干预措施: Ofatumumab (Drug)
结局指标
主要结局
Percentage of Participants With no Change or a Reduction From Baseline in the Number of Gadolinium Enhancing (GdE) Lesions at Month 12 Using Non-responder Imputation
时间窗: Baseline (assessed at screening visit), Month 12
Magnetic Resonance Imaging (MRI) was used to measure presence of new or reduction in number of gadolinium enhancing T1 lesions. Each MRI scan was previewed by a local neuroradiologist. The quality of each scan performed was assessed by a central MRI reading center and evaluated for quality, completeness and adherence to the protocol. A nonresponder imputation (NRI) for missing data approach was applied. NRI assumes that a participant was a treatment failure, i.e. non-responder, if they did not have a valid Month 12 MRI assessment, or if they discontinued the study prematurely and did not have a valid Month 12 MRI assessment.
Percentage of Participants With no Change or a Reduction From Baseline in the Number of Gadolinium Enhancing (GdE) Lesions at Month 12 Based on Observed Data
时间窗: Baseline (assessed at screening visit), Month 12
Magnetic Resonance Imaging (MRI) was used to measure presence of new or reduction in number of gadolinium enhancing T1 lesions. Each MRI scan was previewed by a local neuroradiologist. The quality of each scan performed was assessed by a central MRI reading center and evaluated for quality, completeness and adherence to the protocol. A sensitivity analysis of the primary endpoint was performed based on an observed data approach.
次要结局
- Number of Participants Who Continued Study Treatment From Baseline to Months 6 and 12(Baseline, Month 6, Month 12)
- Change From Baseline in CD19+ B Cell Counts Obtained by FACS(Baseline, Month 6, Month 12)
- Change From Baseline in CD20+ CD3+ T Cell Counts Obtained by FACS(Baseline, Month 6, Month 12)
- Number of Participants With Suicidal Ideation or Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS)(Baseline (all prior history), Post-baseline (up to Month 12))
- Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) Scores at Baseline, Month 6 and Month 12(Baseline, Month 6, Month 12)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs)(From first dose of study drug (Day 1) up to 30 days after last dose (Month 13))