AGNOS: An 18-month, Open-label, Multi-Center Study to Assess the Effect of Ofatumumab 20mg SC Monthly in Treatment Naïve, Very Early Relapsing Remitting Multiple Sclerosis Patients Benchmarked Against Healthy Controls on Select Outcomes.
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 入组人数
- 180
- 试验地点
- 36
- 主要终点
- Percentage of participants achieving NEDA-3 (No Evidence of Disease Activity-3)
研究概览
简要总结
This study will evaluate the impact of ofatumumab in Relapsing Remitting Multiple Sclerosis (RRMS) participants that are very early in the course of their disease using clinical and magnetic resonance imaging (MRI) outcomes. The study will also assess changes in disease using monitoring techniques including digital biometric device use, biomarker analysis and non-conventional MRI. Select outcomes in the ofatumumab treated group will be compared to a group of Healthy participants to determine if there are similarities between the groups after the patients with MS undergo treatment with ofatumumab.
详细描述
The study is an open-label, multi-center, prospective 18-month study in 118 MS participants with early RRMS (defined as within 6 months of diagnosis of clinically definite RRMS) and who are treatment naïve. It is designed to determine if RRMS participants treated with 20 mg subcutaneous monthly ofatumumab during the earliest part of their disease will benefit from the use of ofatumumab as their first disease modifying therapy. Additionally, RRMS patients will be compared to age- and sex-matched healthy participants (n=50) for select outcomes to observe similarities and differences between the groups.
After giving consent, participants will have a 28-day screening/qualification period. If they qualify to continue, they will start study measures including assessments of clinical and magnetic resonance imaging (MRI) metrics and use of a digital monitoring watch. Additionally, samples will be collected for laboratory and biomarker analysis. RRMS participants will begin treatment with ofatumumab for the next 18 months. Healthy participants will undergo similar assessments; however they will not receive any treatment during the course of the study. Over the 18 months, participants will have regular clinical visits with assessments and sample collection. After 18 months in the trial, participants in both groups will have the option to enter into a 12-month extension (up to 30 months total in study) to collect further information on long-term clinical and MRI outcomes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 35 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants eligible for inclusion in this study must meet all of the following criteria:
- •Signed informed consent must be obtained prior to participation in the study
- •Age 18-35 years
- •Patients in the healthy control arm eligible for inclusion must fulfill the following criteria:
- •Able to obtain MRI (HC with abnormal MRI at Screening will be excluded) and use wearable device
- •Able to provide blood sample (no CSF will be collected in HC)
- •Patients in the ofatumumab-treated arm eligible for inclusion must fulfill the following criteria:
- •Diagnosis of RRMS per McDonald Criteria (2010/2017)
- •Within 6 months of diagnosis of clinically definite MS (CDMS)
- •EDSS 0-3.0 (Inclusive)
- •Treatment-naïve to MS DMT
- •Able to obtain MRI and attend study visits at sites
- •Able to use wearable device
- •Able to provide blood sample (and CSF for sub-group n=15)
排除标准
- •Participants in the healthy control arm meeting any of the following criteria are not eligible for inclusion in this study:
- •Confounding medical condition as determined by the investigator
- •RRMS patients fulfilling any of the following exclusion criteria are not eligible for inclusion in this study:
- •Diseases other than multiple sclerosis responsible for the clinical or MRI presentation
- •Patients with neuromyelitis optica, Radiologic/ Clinically Isolated Syndrome, Secondary Progressive or Primary Progressive MS diagnosis
- •Use of experimental or investigational drugs for MS
- •Previous use of Disease Modifying Therapy (DMT) or chemotherapeutic medications for MS
- •Relapse between screening and Baseline visits
- •Known sensitivity to gadolinium; patients with chronic, severe kidney disease
- •Known history of hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes
- •CNS anomalies that are better accounted for by another disease process or MRI anomalies causing clinically apparent impairments
- •Known active malignancies
- •Pregnant or nursing (lactating) women
- •Females of childbearing potential (all women physiologically capable of becoming pregnant) should use effective contraception while receiving ofatumumab and for 6 months after the last treatment of ofatumumab
- •Patients with an active chronic disease (or stable but treated with immune therapy) of the immune system other than MS or with immunodeficiency syndrome
- •Patients with active infections including systemic bacterial, viral (including SARS-CoV-2/COVID-19) or fungal infections, or known to have AIDS or to test positive for HIV antibody at Screening
- •Patients with neurological findings consistent with Progressive Multifocal Leukoencephalopathy (PML), or confirmed PML
- •Patients with IgG or IgM levels below LLN at Screening
- •Patients that have received any live or live-attenuated vaccines within 4 weeks prior to first dose of study drug administration
- •Patients at risk of developing or having reactivation of hepatitis
研究组 & 干预措施
Ofatumumab
Ofatumumab will be provided in an autoinjector for subcutaneous administration. Dosing regimen for this study is an initial dose of 20mg at Baseline/Week 0, followed by Week 1, 2 and every month thereafter, beginning at Week 4 (Month 1) until Month 18. There will be an optional extension of dosing through month 30.
干预措施: Ofatumumab (Drug)
结局指标
主要结局
Percentage of participants achieving NEDA-3 (No Evidence of Disease Activity-3)
时间窗: Month 6 to month 18
A participant is considered as achieved NEDA-3 if the participant has not had a clinical relapse (recurrence of a disease activity after a recovery), has not had an increase in disability and has no new radiological MRI activity (no new occurrences of contrast-enhancing lesions) during study Months 6 to 18.
次要结局
- Number of participants with NEDA (No Evidence of Disease Activity) - Radiological(Month 6 to Month 18)
- Change from Baseline in Gd+ lesion count(Baseline to Month 18 and 30)
- Change from Baseline in Gd+ lesion volume(Baseline to Month 18 and 30)
- Change from Baseline in new/enlarging T2 lesion count(Baseline to Month 18 and 30)
- Change from Baseline in T2 lesion volume(Baseline to Month 18 and 30)
- Change from Baseline in T1 unenhancing lesion volume(Baseline to Month 18 and 30)
- Number of relapses(Baseline to Month 18 and 30)
- Number of participants that were 3-month Disability Worsening-free(Baseline up to Month 18 and 30)
- Number of participants with NEDA (No Evidence of Disease Activity) - Clinical(Month 6 to Month 18)
- Change from Baseline for NeuroQOL(Baseline to Month 18 and 30)
- Change from Baseline for Patient Determined Disease Steps (PDDS)(Baseline to Month 18 and 30)
- Brain volume loss (BVL) assessment (whole brain and regional)(Month 6 to Month 18 and 30)
- Number of participants with treatment emergent adverse events(Baseline up to approximately Month 30)
- Change from Baseline in new unenhancing T1 lesion number(Baseline to Month 18 and 30)