NCT04788615已完成3 期
Open-Label Rater-Blind Randomized Multi-Center Parallel-Arm Active- Comparator Study to Assess the Efficacy and Tolerability of Ofatumumab 20mg SC Monthly vs. First Line DMT - Physician's Choice in the Treatment of Newly Diagnosed RMS
适应症
干预措施
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 185
- 试验地点
- 42
- 主要终点
- Number of participants with no evidence of disease activity (NEDA-3)
研究概览
简要总结
This study will compare ofatumumab vs. European approved platform first line self-administered disease modifying therapy (DMT) in newly diagnosed MS patients
详细描述
The study is a randomized (1:1), open-label, rater-blind, multi-center, prospective, parallel-arm, active comparator study which will consist of 15 months treatment period and a 6 months observational safety extension period, for patients who withdraw ofatumumab for any reason, in 186 total patients with early relapsing multiple sclerosis (RMS) RMS patients are patients who are newly diagnosed or have never been on active treatment at the time of study entry with ≤ 5 years from first MS symptoms.
There is a screening period and patients are randomized to either ofatumumab or first line DMT at baseline. Patients will be treated until the end of study (EOS) or for a maximum duration of 15 months. Patients who prematurely discontinue study drug or comparator will have their end of treatment (EOT) visit and assessments at the time of discontinuation. After ofatumumab or the standard of care comparator (DMT) discontinuation, patients may initiate alternative MS therapy according to local standard of care, if clinically indicated.
Patients who for any reason withdraw from ofatumumab during treatment will be invited to participate in the observational extension safety period for 6 months or until patient re-starts MS treatment with a new DMT treatment. During this period, clinical efficacy after ofatumumab withdrawal will be assessed.
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
- Single (Outcomes Assessor)
盲法说明
The independent EDSS (Expanded disability status scale) rater will be blind to the identity of the treatment throughout the study period. Patient MRI scans read by an independent central MRI reading center.
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent obtained before any assessment
- •Male/female patients, 18 through 55 (inclusive) years of age.
- •Diagnosis of MS according to the 2017 revised McDonald criteria (Thompson et al 2018).
- •Relapsing MS: relapsing-course (RMS), as defined by Lublin et al
- •Treatment Naïve patients, ≤ 5 years since first MS symptom.
- •EDSS score 0-4.0 (inclusive).
- •Patient must be suitable to be treated with one of first line self-administered DMT-physician's choice (glatiramer acetate, IFNs, teriflunomide, DMF, diroximel fumarate according to EMA SmPC) or ofatumumab depending on randomization and physician's choice
- •At least 1 relapse or 1 Gd+ enhanced lesion on T1 in 1 year prior to Screening.
- •Able to obtain MRI assessment.
- •Neurologically stable within 1 month prior to first study drug administration
排除标准
- •Diseases other than multiple sclerosis responsible for the clinical or MRI presentation
- •Progressive MS phenotypes: Patients with primary progressive MS (Polman et al 2011) or SPMS (Lublin et al 2014).
- •Use of other experimental or investigational drugs at the time of enrollment (Screening) or within the prior 30 days, or 5 elimination half-lives, or until the expected pharmacodynamics effect has returned to baseline, whichever is longer
- •Relapse between Screening and Baseline visits
- •Pregnancy or breastfeeding
- •Patients suspected of not being able or willing to cooperate or comply with study protocol requirements in the opinion of the Investigator
- •Women of childbearing potential defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception (methods that result in less than 1% pregnancy rates) while receiving ofatumumab and for 6 months after the last administration. The requirements for contraception for the comparators should also be taken into consideration according to their SmPC.
- •Highly effective methods of contraception include:
- •Total abstinence (when this is in line with the preferred and usual lifestyle of the participant). Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant. Periodic abstinence (e.g. calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception.
- •Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or bilateral tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.
- •Male sterilization (at least 6 months prior to screening). For female participants on the study, the vasectomized male partner should be the sole partner for that participant.
- •(Vasectomized partner is a highly effective birth control method provided that partner is the sole sexual partner of the WOCBP trial participant and that the vasectomized partner has received medical assessment of the surgical success.) - Use of combined, estrogen and progesterone containing (oral, intravaginal, transdermal), hormonal methods of contraception or use of progesterone-only (oral, injectable, implantable) hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception. In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment. Women are considered post-menopausal if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate history of vasomotor symptoms). Women are considered not of childbearing potential if they are post-menopausal or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or bilateral tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of childbearing potential. If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the ICF.
- •Patients with an 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)
- •Patients with an active infection (bacterial, fungal, or viral like hepatitis, HIV or COVID), until the infection is resolved. Where local regulation requires it, Sars-Cov-19 must be ruled out by the PCR test.
- •Patients with neurological findings consistent with Progressive Multifocal Leukoencephalopathy (PML), or confirmed PML
- •Positive results at Screening for serological markers for hepatitis (H) B and C indicating acute or chronic infection:
- •- Hepatitis B virus (HBV) screening should be performed before initiation of treatment.
- •At a minimum, screening should include hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (HBcAb) testing. These can be complemented with other appropriate markers as per local guidelines. Patients with positive hepatitis B serology (either HBsAg or HBcAb) should consult a liver disease expert before the start of treatment and should be monitored and managed following local medical standards to prevent hepatitis B reactivation.
- •- Hepatitis C risk must be ruled out via anti-HC IgG (if positive IgG, HCV-RNA PCR will be performed and if negative, patient can be enrolled) NOTE: If the Investigator suspects false positive hepatitis serology results such as an antibody pattern indicating acute hepatitis infection but no corresponding elevated liver enzymes and no signs or symptoms of liver disease, an infectious disease expert may be consulted. In the case the patient has a record of vaccination including HB, and there is no evidence of acute or chronic hepatitis infection (confirmed by an infectious disease expert), the Investigator must document (in source data and as a comment in the electronic Case Report Form (eCRF) that the serology results are considered false positive and may then enroll the subject.
- •Have received any live or live-attenuated vaccines within 4 weeks prior to first study drug administration
- •Any other disease or condition that could interfere with participation in the study according to the study protocol, or with the ability of the patients to cooperate or comply with the study procedures
- •Any of the following conditions or treatments that may impact the safety of the patient:
- •- History of, or current, significant cardiac disease including cardiac failure (NYHA functional class II-IV), myocardial infarction (within 6 months prior to screening), unstable angina (within 6 months prior to screening), transient ischemic attack (within 6 months prior to screening), stroke, cardiac arrhythmias requiring treatment or uncontrolled arterial hypertension
- •- Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia and clinically significant second or third degree AV block without a pacemaker on screening electrocardiogram (ECG)
- •History of or active severe respiratory disease, including Chronic Obstructive Pulmonary Disease, interstitial lung disease or pulmonary fibrosis
- •Patients with asthma requiring regular treatment with oral steroids
- •Severe hepatic impairment (Child-Pugh class C) or any chronic liver or biliary disease
- •Patients with severe renal impairment (glomerular filtration rate < 30 ml/min/1.73 m2)
- •Any medically unstable condition as determined by the Investigator
- •Any of the following abnormal laboratory values prior to first study drug administration:
- •- Total bilirubin greater than 3 times upper limit of normal (ULN) range, unless in the context of Gilbert's syndrome
- •- Alkaline phosphatase (ALP) greater than 5 times the ULN range
- •- Serum IgG < 500mg/dL (according to central laboratory range)
- •Any other clinically significant laboratory assessment as determined by the Investigator (e.g. significant anemia, neutropenia, thrombocytopenia, signs of impaired bone marrow function)
- •Patients with severe hypoproteinemia e.g. in nephrotic syndrome
- •Patients with any of the following neurologic/psychiatric disorders prior to first study drug administration: - Score "yes" on item 4 or item 5 of the Suicidal Ideation section of the Columbia- Suicide Severity Rating Scale (CSSRS) if this ideation occurred in the past 6 months OR
- •"yes" on any item of the Suicidal Behavior section, except for the "Non-Suicidal Self- Injurious Behavior" (item also included in the Suicidal Behavior section) if this behavior occurred in the past 2 years.
- •History of hypersensitivity to the study drug or any of the excipients or to drugs of similar chemical classes
研究组 & 干预措施
ofatumumab
Experimental
Oftatumumab 20mg auto injector syringes for subcutaneous injection on Day 1, Week 1 and 2, followed by subsequent monthly dosing, starting at Month 1.
干预措施: Ofatumumab (Drug)
First line DMT
Active Comparator
- Glatiramer acetate minimum dose 20mg or maximum dose 40mg twice a day or three times a week or
- Interferon minimum dose 22µg or maximum dose of 0.25mg 3 times a week or once a week or Every second week depending on preparation or
- Peg-Interferon beta-1a minimum dose of 63µg or maximum dose of 125µg every 2 weeks (14 days) or
- Teriflunomide 14 mg once a day or
- Dimethyl fumarate minimum dose of 120mg or maximum dose of 240mg twice a day
- Diroximel fumarate minimum dose of 231mg or maximum dose of 462mg twice a day
干预措施: First line DMT (Drug)
结局指标
主要结局
Number of participants with no evidence of disease activity (NEDA-3)
时间窗: Baseline to 15 month
NEDA-3 (yes/no) is defined as: 1. Absence of confirmed clinical relapse 2. Absence of new MRI activity (Gd+ T1 lesion or new/enlarged T2 lesion) with MRI re-baselined at Month 3 3. Absence of 3-month confirmed disability worsening
次要结局
- Change in expanded disability status scale (EDSS)(Baseline to Month 15)
- Percentage of disability-progression free patients(Baseline to Month 15)
- The number and percentage of patients with Treatment emergent adverse events (TEAE) or adverse events reports(Baseline to Month 15 and 6 months safety follow-up)
- Number of relapses(Baseline to Month 15)
- Annual relapse rate(Baseline to Month 15)
- Percentage of relapse-free patients and proportion of relapse free patients with MRI activity free(Month 3, Month 9 and Month 15)
- Time to 3 month Confirmed Disability Worsening (CDW) and time to 6-month Confirmed Disability Worsening (CDW)(Baseline to Month 3 and to Month 6)
- Number of Gd+ T1 lesions of brain(Baseline to Month 15)
- Volume of Gd+ T1 lesions of brain(Baseline to Month 15)
- Number of new/enlarging T2 lesions of brain(Baseline to Month 15)
- Volume of new enlarging T2 lesions of brain(Baseline to Month 15)
- Mean time to first relapse(Baseline to Month 15)
- Percentage of SAEs, and SAEs with hospitalizations(Baseline to Month 15 and 6 months safety follow-up)
- Percentage of treatment compliance of participants(Baseline to Month 15)
- Percentage of patient with AEs(Baseline to Month 15 and 6 months safety follow-up)
- Percentage of withdrawn patients(Baseline to Month 15)
- Percentage of treatment discontinuation or interruptions(Baseline to Month 15)
研究者
研究点 (42)
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