A Randomized, Double-blind, Double-dummy, Parallel-group Study Comparing the Efficacy and Safety of Ofatumumab Versus Teriflunomide in Patients With Relapsing Multiple Sclerosis.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 955
- 试验地点
- 1
- 主要终点
- Annualized Relapse Rate (ARR)
研究概览
简要总结
To compare the efficacy and safety of ofatumumab administered subcutaneously (sc) every 4 weeks versus teriflunomide administered orally once daily in patients with relapsing multiple sclerosis
详细描述
This was a randomized, double-blind, double-dummy, active comparatorcontrolled, parallel-group, multi-center study with variable treatment duration in approximately 900 patients with relapsing multiple sclorosis (RMS). The maximal treatment duration in the study for an individual patient was 2.5 years. Eligible patients were randomized to receive either experimental ofatumumab subcutaneous (s.c.) injections every 4 weeks or active comparator teriflunomide orally once daily. The dose regimen for ofatumumab for this study was a loading dose regimen of 20 mg at Day 1, Day 7 and Day 14, followed by a maintenance dose regimen of 20 mg administered every 4 weeks starting at Week 4. In order to blind for the different formulations, double-dummy masking was used, i.e., all patients will take injections (containing either active ofatumumab or placebo) and oral capsules (containing either active teriflunomide or placebo).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Male or female patients aged 18 to 55 years at Screening
- •Diagnosis of multiple sclerosis (MS)
- •Relapsing MS: relapsing-remitting MS (RRMS) or secondary progressive MS (SPMS) with disease activity
- •Documentation of at least: 1 relapse during the previous 1 year OR 2 relapses during the previous 2 years OR a positive gadolinium-enhancing MRI scan during the year prior to randomization
- •Disability status at Screening with an Expanded Disability Status Scale (EDSS) score of 0 to 5.5
- •Neurologically stable within 1 month prior to randomization
排除标准
- •Patients with primary progressive MS or SPMS without disease activity
- •Disease duration of more than 10 years in patients with an EDSS score of 2 or less
- •Patients with an active chronic disease of the immune system other than MS
- •Patients at risk of developing or having reactivation of hepatitis
- •Patients with active systemic infections or with neurological findings consistent with PML
研究组 & 干预措施
OMG 20 mg
Ofatumumab 20 mg pre-filled syringes for subcutaneous injectionon on days 1
,7 ,14, week 4 and every 4 weeks thereafter and a teriflunomide-matching placebo, taken orally once daily
干预措施: Ofatumumab subcutaneous injection (Drug)
OMG 20 mg
Ofatumumab 20 mg pre-filled syringes for subcutaneous injectionon on days 1
,7 ,14, week 4 and every 4 weeks thereafter and a teriflunomide-matching placebo, taken orally once daily
干预措施: Teriflunomide-matching placebo capsules (Drug)
TER 14 mg
Teriflunomide 14 mg oral capsule taken once daily and matching placebo for subcutaneous injections to ofatumumab on days 1, 7, 14, week 4 and every 4 weeks thereafter
干预措施: Teriflunomide capsule (Drug)
TER 14 mg
Teriflunomide 14 mg oral capsule taken once daily and matching placebo for subcutaneous injections to ofatumumab on days 1, 7, 14, week 4 and every 4 weeks thereafter
干预措施: Matching placebo of ofatumumab subcutaneous injections (Drug)
结局指标
主要结局
Annualized Relapse Rate (ARR)
时间窗: Baseline up to 2.5 years
ARR was the number of confirmed relapses in a year, calculated as the total number of relapses for all participants in the treatment group divided by the total participant-years of time in study. A confirmed MS relapse was defined as one accompanied by a clinically-relevant change in the EDSS performed by the Independent EDSS rater, i.e. an increase of at least 0.5 points on the EDSS score, or an increase of 1 point on two functional scores or 2 points on one functional score (excluding changes involving bowel/bladder or cerebral functional system). Comparisons were made to the previous rating (the last EDSS rating that did not occur during a relapse).
次要结局
- 3-month Confirmed Disability Worsening (3mCDW) Based on EDSS - Pooled Data(Baseline, every 3 months up to 2.5 years)
- 6-month Confirmed Disability Worsening (6mCDW) Based on EDSS - Study COMB157G2302(Baseline, every 3 months up to 2.5 years)
- Number of Gadolinium-enhancing T1 Lesions Per MRI Scan(Baseline, yearly up to 2.5 years)
- 3-month Confirmed Disability Worsening (3mCDW) Based on EDSS - Study COMB157G2302(Baseline, every 3 months up to 2.5 years)
- Number of New or Enlarging T2 Lesions on MRI Per Year (Annualized Lesion Rate)(Baseline, yearly up to 2.5 years)
- Participants With Confirmed Relapse(Baseline up to 2.5 years)
- Annualized Relapse Rate (ARR) >8 Weeks After Onset of Treatment(Baseline up to 2.5 years)
- 6-month Confirmed Disability Improvement (6mCDI ) Based on EDSS - Pooled Data(Baseline, every 3 months up to 2.5 years)
- 6-month Confirmed Disability Improvement (6mCDI ) Based on EDSS - Study COMB157G2302(Baseline, every 3 months up to 2.5 years)
- Annualized Rate of Brain Volume Loss Based on Assessments of Percent Brain Volume Change From Baseline(Baseline, Months 12 and 24)
- Number of New or Enlarging T2 Lesions on MRI Per Year From Month 12 Until End of Study (EOS)(Month 12 up to 2.5 years)
- Multiple Sclerosis Impact Scale (MSIS-29) Physical Impact Score Change From Baseline(Baseline, every 6 months up to 2.5 years)
- Annualized Relapse Rates (ARR) by NfL High-low Subgroups - Pooled Data(Baseline up to 2.5 years)
- Neurofilament Light Chain (NfL) Concentration in Serum(Month 3, 12 and 24)
- 3-month Confirmed Disability Worsening (3mCDW) Based on EDSS > 8 Weeks After Onset of Treatment - Pooled Data(Baseline up to 2.5 years)
- Multiple Sclerosis Impact Scale (MSIS-29) Psychological Impact Score Change From Baseline(Baseline, every 6 months up to 2.5 years)
- Pharmacokinetic (PK) Concentrations of Ofatumumab(Baseline, Weeks 4, 12, 24, 48, 96)
- 6-month Confirmed Disability Worsening (6mCDW) Based on EDSS - Pooled Data(Baseline, every 3 months up to 2.5 years)
- 6-month Confirmed Cognitive Decline on Symbol Digit Modalities Test (SDMT) - Pooled Data(Baseline, every 6 months up to 2.5 years)
- Change in Cognitive Performance Measured by the Symbol Digit Modalities Test (SDMT) - Pooled Data(Baseline up to 2.5 years)
- 6-month Confirmed Disability Improvement (6mCDI) Sustained Until End of Study (EOS) as Measured by EDSS - Pooled Data(Baseline, every 3 months up to 2.5 years)
- 6-month Confirmed Disability Worsening (6mCDW) Based on EDSS > 8 Weeks After Onset of Treatment - Pooled Data(Baseline up to 2.5 years)
- Percent Change in T2 Lesion Volume Relative to Baseline(Baseline, Month 12, Month 24)
- Number of New or Enlarging T2 Lesions Per Year by NfL High-low Subgroups - Pooled Data(Baseline, yearly up to 2.5 years)
- 6-month Confirmed Disability Worsening (6mCDW) or 6-month Confirmed Cognitive Decline (6mCCD) - Pooled Data(Baseline up to 2.5 years)
- 6-month Confirmed Worsening of at Least 20% in the Timed 25-Foot Walk (T25FW) - Pooled Data(Baseline, every 3 months up to 2.5 years)
- 6-month Confirmed Worsening of at Least 20% in the 9-Hole Peg Test (9HPT) - Pooled Data(Baseline, every 6 months up to 2.5 years)
- No Evidence of Disease Activity (NEDA-4)(Baseline, Month 12, Month 24)
- Brain Volume Loss by NfL High-low Subgroups - Pooled Data(Baseline, Months 12 and 24)