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临床试验/NCT04951622
NCT04951622招募中3 期

Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Nipocalimab Administered to Adults With Generalized Myasthenia Gravis

Janssen Research & Development, LLC181 个研究点 分布在 9 个国家目标入组 199 人开始时间: 2021年7月15日最近更新:
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适应症
干预措施
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试验速览

阶段
3 期
状态
招募中
入组人数
199
试验地点
181
主要终点
Double-blind (DB) Phase: Average Change From Baseline in Myasthenia Gravis - Activities of Daily Living (MG-ADL) Total Score Over Weeks 22, 23, and 24
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验相关资讯

研究概览

简要总结

The purpose of this study is to evaluate the efficacy and safety of nipocalimab compared to placebo in participants with generalized myasthenia gravis (gMG). The purpose of the subcutaneous substudy is to evaluate how well it works in the body (pharmacodynamic [PD]) when given as an injection under the skin (subcutaneous) compared to when given through a vein (intravenous) in participants with gMG.

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 —（Adult, Older Adult）
性别
All
接受健康志愿者
否

入选标准

  • •Diagnosis of myasthenia gravis (MG) with generalized muscle weakness meeting the clinical criteria for generalized myasthenia gravis (gMG) as defined by the Myasthenia Gravis Foundation of America (MGFA) Clinical Classification Class II a/b, III a/b, or IVa/b at screening
  • •Myasthenia Gravis - Activities of Daily Living (MG-ADL) score of greater than or equal to (>=) 6 at screening and baseline
  • •Has sufficient venous access to allow drug administration by infusion and blood sampling as per the protocol
  • •A woman of childbearing potential must have a negative highly sensitive serum (beta-human chorionic gonadotropin [beta-hCG]) at screening and a negative urine pregnancy test at Day 1 prior to administration of study intervention
  • •A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum 90 days after receiving the last administration of study intervention
  • •For the SC Substudy (Cohort 1 and Cohort 2): Has reasonable abdominal skin area for SC administration
  • •For the SC Substudy (Cohort 1 and Cohort 2): Participants must be willing to comply with maintaining their stable dose of corticosteroids and/or immunosuppressants for the initial 8 weeks of the SC substudy, that is, through the SC Week 8 visit

排除标准

  • •Has any confirmed or suspected clinical immunodeficiency syndrome not related to treatment of his/her gMG, or has a family history of congenital or hereditary immunodeficiency unless confirmed absent in the participant
  • •Has MGFA Class I disease or presence of MG crisis (MGFA Class V) at screening, history of MG crisis within 1 month of screening, or fixed weakness (and/or 'burnt out' MG)
  • •Has had a thymectomy within 12 months prior to screening, or thymectomy is planned during the study
  • •Has known allergies, hypersensitivity, or intolerance to nipocalimab or its excipients
  • •Has experienced myocardial infarction, unstable ischemic heart disease, or stroke within 12 weeks of screening
  • •For the SC Substudy (Cohort 1): Participants who have undergone a recent tapering of their concomitant MG medication in the OLE
  • •For the SC Substudy (Cohort 1): Participants deteriorating during the OLE in the month prior to SC Dose 1 of the SC substudy such that they meet the criteria for clinical deterioration
  • •For the SC Substudy (Cohort 2): History of an unprovoked pulmonary embolism within 1 year prior to screening or history of recurrent deep vein thrombosis (DVT)

研究组 & 干预措施

Nipocalimab

Experimental

Double-blind Placebo-controlled Phase: Participants will receive nipocalimab intravenous (IV) infusions once every 2 weeks (q2w) up to 24 weeks during double-blind placebo-controlled phase.

Open-label Extension (OLE) Phase: Participants who complete the double-blind placebo-controlled phase will enter the OLE phase and will have the option to continue to receive nipocalimab q2w IV infusion till study end or enter the nipocalimab SC substudy.

干预措施: Nipocalimab (Drug)

Placebo

Placebo Comparator

Double-blind Placebo-controlled Phase: Participants will receive matching placebo of nipocalimab IV infusion q2w up to 24 weeks during double-blind placebo-controlled phase.

干预措施: Placebo (Drug)

Nipocalimab Subcutaneous (SC)

Experimental

OLE Phase: Participants from Cohort 1 will receive nipocalimab subcutaneous liquid in vial (SC-LIV) qw until Week 8. Participants with gMG from Cohort 2 who have not received nipocalimab previously, will receive nipocalimab SC-LIV until Week 8. Participants who complete the 8-week treatment period will have the opportunity to continue receiving nipocalimab SC-LIV qw in the Long term extension (LTE) period.

干预措施: Nipocalimab SC-LIV (Drug)

结局指标

主要结局

Double-blind (DB) Phase: Average Change From Baseline in Myasthenia Gravis - Activities of Daily Living (MG-ADL) Total Score Over Weeks 22, 23, and 24

时间窗: Baseline, Weeks 22, 23, and 24

Average change from baseline over multiple timepoints (Weeks 22, 23, and 24) was reported in this outcome measure. The MG-ADL provided a rapid assessment of the participant's MG symptom severity of eight functions (talking, chewing, swallowing, breathing, impairment of ability to brush teeth or comb hair, impairment of ability to arise from a chair, double vision, eyelid droop) rated on a 4-point scale ranging from 0 (normal) to 3 (severe). MG-ADL total score was sum of 8 individual items, which ranging from 0 to 24. A higher score indicated greater symptom severity. Baseline was defined as the average of the screening and Day 1 total scores.

Double-blind (DB) Phase: Average Change From Baseline in Myasthenia Gravis - Activities of Daily Living (MG-ADL) Total Score Over Weeks 22, 23, and 24

时间窗: Baseline, Weeks 22, 23, and 24

Average change from baseline over multiple timepoints (Weeks 22, 23, and 24) was reported in this outcome measure. The MG-ADL provided a rapid assessment of the participant's MG symptom severity of eight functions (talking, chewing, swallowing, breathing, impairment of ability to brush teeth or comb hair, impairment of ability to arise from a chair, double vision, eyelid droop) rated on a 4-point scale ranging from 0 (normal) to 3 (severe). MG-ADL total score was sum of 8 individual items, which ranging from 0 to 24. A higher score indicated greater symptom severity. Baseline was defined as the average of the screening and Day 1 total scores.

Sub Study: Percent Change in Anti-AChR Autoantibody Titer From Pre-first Nipocalimab Dose on Day 1 up to Week 8 (Day 57)

时间窗: From pre-first nipocalimab dose on Day 1 up to Week 8 (Day 57)

Sub Study: Percent Change in Total IgG Levels From Pre-first Nipocalimab Dose on Day 1 up to Week 8 (Day 57)

时间窗: From pre-first nipocalimab dose on Day 1 up to Week 8 (Day 57)

次要结局

  • DB Phase: Percentage of Participants With Myasthenia Gravis - Activities of Daily Living (MG-ADL) Score of 0 or 1 Over Time(Baseline up to Week 24)
  • DB Phase: Average Change From Baseline in Quantitative Myasthenia Gravis (QMG) Score Over Weeks 22 and 24(Baseline, Weeks 22, and 24)
  • DB Phase: Percentage of Participants Who Had Achieved at Least a 2-point Average Improvement From Baseline in Myasthenia Gravis - Activities of Daily Living (MG-ADL) Total Score Over Weeks 22, 23, and 24(Weeks 22, 23, and 24)
  • DB Phase: Percentage of Participants Who Had Achieved an Improvement of Greater Than or Equal to (>=) 2 Points in the Myasthenia Gravis - Activities of Daily Living (MG-ADL) Total Score at Week 1 and/or Week 2(Weeks 1 and 2)
  • DB Phase: Percentage of Participants Who Had an Improvement of >= 2 Points in the MG-ADL Total Score From Week 4 Through Week 24 With no More Than 2 Non-consecutive Excursions Allowed Between Weeks 6 Through 23(From Week 4 up to Week 24)
  • DB Phase: Percentage of Participants Who Had Achieved at Least a 50 Percent (%) Average Improvement From Baseline in the Myasthenia Gravis - Activities of Daily Living (MG-ADL) Total Score Over Weeks 22, 23, and 24(Weeks 22, 23, and 24)
  • Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)(From start of treatment (DB phase Day 1) up to 4 years 9 months)
  • Percentage of Participants With Treatment-emergent Serious Adverse Events (TESAEs)(From start of treatment (DB phase Day 1) up to 4 years 9 months)
  • Percentage of Participants With AEs of Special Interest (AESIs)(From start of treatment (DB phase Day 1) up to 4 years 9 months)
  • Number of Participants With Change in Vital Signs(From start of treatment (DB phase Day 1) up to 4 years 9 months)
  • Number of Participants With Change in Clinical Laboratory Values(From start of treatment (DB phase Day 1) up to 4 years 9 months)
  • Number of Participants With Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Score(From start of treatment (Day 1) up to 4 years 9 months)
  • DB Phase: Percentage of Participants Who Had an Improvement of >= 3 Points in Quantitative Myasthenia Gravis (QMG) Score From Baseline, at Week 2 Through Week 24, With No More Than 2 Non-consecutive Excursions Allowed Between at Weeks 4 Through Week 22(Baseline, Week 2 up to Week 24)
  • DB Phase: Average Change From Baseline in the Fatigue Items of the Quality of Life in Neurological Disorders (Neuro-QoL) Fatigue Scale Total Score Over Weeks 22 and 24(Baseline up to Weeks 22, and 24)
  • DB Phase: Average Change From Baseline in the Revised Myasthenia Gravis Quality of Life (Revised) Instrument (MG-Qol15r) Score Over Weeks 22 And 24(Baseline up to Weeks 22, and 24)
  • DB Phase: Change From Baseline in the Visual Analog Scale (VAS) Score of European Quality of Life (EuroQol) 5-Dimension 5-Level (EQ-5D-5L) Scale Over 24 Weeks(Baseline up to Week 24)
  • DB Phase: Change From Baseline in the Health Status Index of the EuroQol 5-Dimension 5-Level (EQ-5D-5L) Scale Over 24 Weeks(Baseline up to Week 24)
  • DB Phase: Percentage of Participants With Myasthenia Gravis - Activities of Daily Living (MG-ADL) Score of 0 or 1 at Any Time(Baseline up to Week 24)
  • DB Phase: Percentage of Participants With Myasthenia Gravis - Activities of Daily Living (MG-ADL) Score of 0 or 1 at 50% of Timepoints(Baseline up to Week 24)
  • DB Phase: Percentage of Participants With Myasthenia Gravis - Activities of Daily Living (MG-ADL) Score of 0 or 1 at 75% of Timepoints(Baseline up to Week 24)
  • Serum Concentrations of Nipocalimab Over Time(DB Phase: Predose and 45 minutes post-dose on Day 1, Weeks 2, 4, 8, 12,16, 20, 24;OL Phase: Predose on Day 1, Weeks 8, 16, 24, 36, 48, 60, 72, 84, and 96)
  • Number of Participants With Antibodies to Nipocalimab (Anti-Drug Antibodies [ADAs] and Neutralizing Antibodies [NAbs])(From start of treatment (Day 1) up to 4 years 9 months)
  • Percent Change From Baseline in Total Serum Immunoglobulin G (IgG) Concentrations(Baseline up to 4 years 9 months)
  • Change From Baseline in Levels of Autoantibodies Associated With Generalized Myasthenia Gravis (gMG)(Baseline up to 4 years 9 months)
  • Change From Baseline in Myasthenia Gravis - Activities of Daily Living (MG-ADL) Score as a Function of IgG(Baseline up to 4 years 9 months)
  • Change From Baseline in Quantitative Myasthenia Gravis (QMG) Score as a Function of Immunoglobulin G (IgG)(Baseline up to 4 years 9 months)
  • Change From Baseline in Myasthenia Gravis - Activities of Daily Living (MG-ADL) Score as a Response to Percent Change in Autoantibody Levels in Seropositive Participants Treated With Nipocalimab(Baseline up to 4 years 9 months)
  • Change From Baseline in QMG Score as a Response to Percent Change in Autoantibody Levels in Seropositive Participants Treated With Nipocalimab(Baseline up to 4 years 9 months)
  • DB Phase: Change From Baseline in the Health Status Index of the EuroQol 5-Dimension 5-Level (EQ-5D-5L) Scale Over 24 Weeks(Baseline up to Week 24)
  • DB Phase: Percentage of Participants With Myasthenia Gravis - Activities of Daily Living (MG-ADL) Score of 0 or 1 Over Time(Baseline up to Week 24)
  • DB Phase: Percentage of Participants With Myasthenia Gravis - Activities of Daily Living (MG-ADL) Score of 0 or 1 at Any Time(Baseline up to Week 24)
  • DB Phase: Percentage of Participants With Myasthenia Gravis - Activities of Daily Living (MG-ADL) Score of 0 or 1 at 50% of Timepoints(Baseline up to Week 24)
  • DB Phase: Percentage of Participants With Myasthenia Gravis - Activities of Daily Living (MG-ADL) Score of 0 or 1 at 75% of Timepoints(Baseline up to Week 24)
  • Serum Concentrations of Nipocalimab Over Time(DB Phase: Predose and 45 minutes post-dose on Day 1, Weeks 2, 4, 8, 12,16, 20, 24;OL Phase: Predose on Day 1, Weeks 8, 16, 24, 36, 48, 60, 72, 84, and 96)
  • Change From Baseline in Levels of Autoantibodies Associated With Generalized Myasthenia Gravis (gMG)(Baseline up to 4 years 9 months)
  • Change From Baseline in Myasthenia Gravis - Activities of Daily Living (MG-ADL) Score as a Function of IgG(Baseline up to 4 years 9 months)
  • Change From Baseline in Quantitative Myasthenia Gravis (QMG) Score as a Function of Immunoglobulin G (IgG)(Baseline up to 4 years 9 months)
  • Change From Baseline in Myasthenia Gravis - Activities of Daily Living (MG-ADL) Score as a Response to Percent Change in Autoantibody Levels in Seropositive Participants Treated With Nipocalimab(Baseline up to 4 years 9 months)
  • Change From Baseline in QMG Score as a Response to Percent Change in Autoantibody Levels in Seropositive Participants Treated With Nipocalimab(Baseline up to 4 years 9 months)
  • DB Phase: Average Change From Baseline in the Revised Myasthenia Gravis Quality of Life (Revised) Instrument (MG-Qol15r) Score Over Weeks 22 And 24(Baseline up to Weeks 22, and 24)
  • DB Phase: Change From Baseline in the Visual Analog Scale (VAS) Score of European Quality of Life (EuroQol) 5-Dimension 5-Level (EQ-5D-5L) Scale Over 24 Weeks(Baseline up to Week 24)
  • DB Phase: Percentage of Participants Who Had Achieved at Least a 2-point Average Improvement From Baseline in Myasthenia Gravis - Activities of Daily Living (MG-ADL) Total Score Over Weeks 22, 23, and 24(Weeks 22, 23, and 24)
  • DB Phase: Percentage of Participants Who Had Achieved an Improvement of Greater Than or Equal to (>=) 2 Points in the Myasthenia Gravis - Activities of Daily Living (MG-ADL) Total Score at Week 1 and/or Week 2(Weeks 1 and 2)
  • DB Phase: Percentage of Participants Who Had an Improvement of >= 2 Points in the MG-ADL Total Score From Week 4 Through Week 24 With no More Than 2 Non-consecutive Excursions Allowed Between Weeks 6 Through 23(From Week 4 up to Week 24)
  • DB Phase: Percentage of Participants Who Had Achieved at Least a 50 Percent (%) Average Improvement From Baseline in the Myasthenia Gravis - Activities of Daily Living (MG-ADL) Total Score Over Weeks 22, 23, and 24(Weeks 22, 23, and 24)
  • Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)(From start of treatment (DB phase Day 1) up to 4 years 9 months)
  • Percentage of Participants With Treatment-emergent Serious Adverse Events (TESAEs)(From start of treatment (DB phase Day 1) up to 4 years 9 months)
  • Percentage of Participants With AEs of Special Interest (AESIs)(From start of treatment (DB phase Day 1) up to 4 years 9 months)
  • Number of Participants With Change in Clinical Laboratory Values(From start of treatment (DB phase Day 1) up to 4 years 9 months)
  • Number of Participants With Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Score(From start of treatment (Day 1) up to 4 years 9 months)
  • DB Phase: Percentage of Participants Who Had an Improvement of >= 3 Points in Quantitative Myasthenia Gravis (QMG) Score From Baseline, at Week 2 Through Week 24, With No More Than 2 Non-consecutive Excursions Allowed Between at Weeks 4 Through Week 22(Baseline, Week 2 up to Week 24)
  • DB Phase: Average Change From Baseline in the Fatigue Items of the Quality of Life in Neurological Disorders (Neuro-QoL) Fatigue Scale Total Score Over Weeks 22 and 24(Baseline up to Weeks 22, and 24)
  • Sub Study: Change From Baseline in Patient Global Impression of Severity (PGIS) Scale Score up to Week 8 (Day 57)(From baseline (pre-first nipocalimab dose on Day 1) up to Week 8 (Day 57))
  • Sub Study: Change From Baseline in Patient Global Impression of Change (PGIC) Scale Score up to Week 8 (Day 57)(From baseline (pre-first nipocalimab dose on Day 1) up to Week 8 (Day 57))
  • Sub Study: Change From Baseline in MG-QoL Participant-Reported Outcome Measures up to Week 8 (Day 57)(From baseline (pre-first nipocalimab dose on Day 1) up to Week 8 (Day 57))
  • Sub Study: Change From Baseline in EQ-5D-5L Participant-Reported Outcome Measures up to Week 8 (Day 57)(From baseline (pre-first nipocalimab dose on Day 1) up to Week 8 (Day 57))
  • Sub Study: Percent Change in Total IgG Levels From Pre-first Nipocalimab Dose on Day 1 up to Week 8 (Day 57)(From pre-first nipocalimab dose on Day 1 up to Week 8 (Day 57))
  • Sub Study: Percent Change in Anti-AChR Autoantibody Titer From Pre-first Nipocalimab Dose on Day 1 up to Week 8 (Day 57)(From pre-first nipocalimab dose on Day 1 up to Week 8 (Day 57))
  • Sub Study: Number of Participants With Abnormalities in Vital Signs(Up to SC Week 8 (Day 57))
  • Sub Study: Number of Participants With Abnormalities in Physical Examinations(Up to SC Week 8 (Day 57))
  • Sub Study: Number of Participants With Abnormalities in Laboratory Parameters(Up to SC Week 8 (Day 57))
  • Sub Study: Numeric Pain Rating Scale (NPRS) Assessment With SC Use of Nipocalimab(Up to SC Week 8 (Day 57))
  • Sub Study: Number of Participants With Injection Site-Reactions(Up to SC Week 8 (Day 57))
  • Sub Study: Change From Baseline in MG-ADL Clinician-Reported Outcome Measures up to Week 8 (Day 57)(From baseline (pre-first nipocalimab dose on Day 1) up to Week 8 (Day 57))
  • Sub Study: Number of Participants With Treatment-Emergent AEs(Up to SC Week 8 (Day 57))
  • Sub Study: Change From Baseline in QMG Clinician-Reported Outcome Measures up to Week 8 (Day 57)(From baseline (pre-first nipocalimab dose on Day 1) up to Week 8 (Day 57))
  • Sub Study: Change From Baseline in Myasthenia Gravis Foundation of America (MGFA) Clinician-Reported Measures up to Week 8 (Day 57)(From baseline (pre-first nipocalimab dose on Day 1) up to Week 8 (Day 57))
  • Sub Study: Change From Baseline in C-SSRS Clinician-Reported Outcome Measures up to Week 8 (Day 57)(From baseline (pre-first nipocalimab dose on Day 1) up to Week 8 (Day 57))
  • Sub Study: Change From Baseline in Neuro-QoL Participant-Reported Outcome Measures up to Week 8 (Day 57)(From baseline (pre-first nipocalimab dose on Day 1) up to Week 8 (Day 57))

研究者

申办方类型
Industry
责任方
Sponsor

研究点 (181)

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