A Phase 1 Randomized Study of MEDI-551 in Subjects With Relapsing Forms of Multiple Sclerosis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs)
研究概览
简要总结
The purpose of this study is to evaluate the safety and tolerability of ascending intravenous (IV) and subcutaneous (SC) doses of MEDI-551 in adult subjects with relapsing forms of multiple sclerosis (MS).
详细描述
This is a Phase 1, multicenter, multinational, randomized, blinded, placebo-controlled, dose-escalation study to evaluate the safety and tolerability of IV and SC doses of MEDI-551 in adult subjects with relapsing forms of MS.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed relapsing form of MS (ie, RRMS, SPMS, PRMS, or CIS) according to revised 2010 McDonald criteria and MRI brain lesions consistent with MS on screening
- •At least 1 documented relapse within the past 3 years prior to screening
- •EDSS between 0.0 and 6.5 at screening
- •Have no more than 20 Gd-enhancing T1 brain lesions detected by cranial MRI scan
排除标准
- •Subjects with impaired renal function
- •Major surgery within 8 weeks of the screening visit
- •Subjects who are unable to undergo cranial MRI scan
- •A history of hypersensitivity to Gd-containing MRI contrast agents
- •Has received within 1 year prior to screening: monoclonal antibodies, experimental B-cell depleting agents, or treatment with natalizumab (Tysabri) for greater than 3 months
- •Receiving monthly methylprednisone or equivalent glucocorticoid for disease modification of a relapsing form of MS
- •Known sensitivity to acetaminophen/paracetamol, diphenhydramine or equivalent antihistamine, methylprednisolone or equivalent glucocorticoid, or to any component of the investigational drug
- •Diagnosis of PPMS, neuromyelitis optica, or other non-MS variant of neuro-inflammatory or demyelinating diseases
- •Any history of opportunistic infection or the presence of active infection within two months prior to screening or any herpes zoster infection that has not resolved within 12 weeks prior to screening
- •Any clinically significant findings during the screening phase, including physical, neurological, laboratory, or ECG examination as per protocol
研究组 & 干预措施
MEDI-551 30 MG-IV
Participants received a fixed IV dose of 30 milligram (mg) MEDI-551 infused on Days 1 and 15.
干预措施: MEDI-551 30 MG-IV (Drug)
MEDI-551 60 MG-SC
Participants received SC injection of 60 mg MEDI-551 on Day 1.
干预措施: MEDI-551 60 MG-SC (Drug)
MEDI-551 100 MG-IV
Participants received a fixed IV dose of 100 mg MEDI-551 infused on Days 1 and 15.
干预措施: MEDI-551 100 MG-IV (Drug)
MEDI-551 300 MG-SC
Participants received SC injection of 300 mg MEDI-551 on Day 1.
干预措施: MEDI-551 300 MG-SC (Drug)
MEDI-551 600 MG-IV
Participants received a fixed IV dose of 600 mg MEDI-551 infused on Days 1 and 15.
干预措施: MEDI-551 600 MG-IV (Drug)
PLACEBO-IV-SC
Participants received either a fixed IV dose of placebo matching with MEDI- 551 on Days 1 and 15 or SC injection on Day 1.
干预措施: PLACEBO-IV-SC (Drug)
结局指标
主要结局
Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs)
时间窗: From study drug administration (Day 1) through the long term follow up period (up to 18 months after early discontinuation visit or 24 week treatment period).
A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death, life-threatening, initial or prolonged inpatient hospitalization, persistent or significant disability or incapacity, congenital anomaly or birth defect in the offspring of a participant who received the study drug. The TESAEs were the events between administration of study drug (Day 1) and long term follow up period (up to 18 months after early discontinuation visit or 24-week treatment period) that were absent before treatment or that worsened relative to pre-treatment state. The AEs were summarized using Medical Dictionary for Regulatory Activities version 19.0
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
时间窗: From study drug administration (Day 1) through the end of treatment period (Day 169)
An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A TEAE were the events between administration of study drug (Day 1) and Day 169 that were absent before treatment or that worsened relative to pre-treatment state. The AEs were summarized using Medical Dictionary for Regulatory Activities version 19.0
Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs
时间窗: From study drug administration (Day 1) through the end of treatment period (Day 169)
Any clinically significant change in laboratory evaluations were recorded as AEs. The following parameters were analyzed for laboratory evaluations: haematology, serum chemistry, and urinalysis. Number of participants with TEAEs related to laboratory evaluations were reported.
Number of Participants With Vital Sign Abnormalities Reported as TEAEs
时间窗: From study drug administration (Day 1) through the end of treatment period (Day 169)
Vital sign parameters included blood pressure, temperature, pulse rate, and respiratory rate. The number of participants with TEAEs related to vital signs in participants were reported.
次要结局
- Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI-551(Predose (Day 1) and Postdose (IV Cohorts only), Days 4 (SC Cohorts only), 8, 15 Predose and Postdose (IV Cohorts only), 29, 57, 85, 113, 141, and 169)
- Absolute Subcutaneous Bioavailability (F%) of MEDI-551(Predose (Day 1) and Days 4, 8, 15, 29, 57, 85, 113, 141, and 169)
- Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC 0-last) of MEDI-551(Predose (Day 1) and Postdose (IV Cohorts only), Days 4 (SC Cohorts only), 8, 15 Predose and Postdose (IV Cohorts only), 29, 57, 85, 113, 141, and 169)
- Dose Normalized Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUC 0-infinity/D) of MEDI-551(Predose (Day 1) and Postdose (IV Cohorts only), Days 4 (SC Cohorts only), 8, 15 Predose and Postdose (IV Cohorts only), 29, 57, 85, 113, 141, and 169)
- Clearance of MEDI-551(Predose (Day 1) and Postdose (IV Cohorts only), Days 4 (SC Cohorts only), 8, 15 Predose and Postdose (IV Cohorts only), 29, 57, 85, 113, 141, and 169)
- Terminal Elimination Half-life (t1/2) of MEDI-551(Predose (Day 1) and Postdose (IV Cohorts only), Days 4 (SC Cohorts only), 8, 15 Predose and Postdose (IV Cohorts only), 29, 57, 85, 113, 141, and 169)
- Absolute CD20 B-cell Count at Baseline(Baseline (Days -28 to -1))
- Time to 90 Percent (%) CD20 B-cell Depletion(Baseline (Days -28 to -1) to long-term follow-up (LTFU) (Up to 18 months after EDV or 24 Week treatment period))
- Duration of Suppression Greater Than or Equal to 90 % of CD20 B-cell Count(Baseline (Days -28 to -1) to LTFU (Up to 18 months after EDV or 24 Week treatment period))
- Number of Participants Positive for Anti-Drug Antibodies to MEDI-551(Days 1, 29, 85 and 169)
- Maximum Observed Serum Concentration (Cmax) of MEDI-551(Predose (Day 1) and Postdose (IV Cohorts only), Days 4 (SC Cohorts only), 8, 15 Predose and Postdose (IV Cohorts only), 29, 57, 85, 113, 141, and 169)
- Area Under the Plasma Concentration-time Curve From Zero to Infinity (AUC 0-infinity) of MEDI-551(Predose (Day 1) and Postdose (IV Cohorts only), Days 4 (SC Cohorts only), 8, 15 Predose and Postdose (IV Cohorts only), 29, 57, 85, 113, 141, and 169)
- Maximum Change From Baseline in Absolute CD20 of Peripheral Blood B-cell Count to LTFU(Baseline (Days -28 to -1) to LTFU (Up to 18 months after EDV or 24 Week treatment period))