Efficacy and Safety of Pozelimab and Cemdisiran Combination Therapy and Cemdisiran Monotherapy in Patients With Symptomatic Generalized Myasthenia Gravis
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 288
- 试验地点
- 221
- 主要终点
- Change in Myasthenia Gravis-Activities of Daily Living (MG-ADL) total score
研究概览
简要总结
This study is researching the experimental drugs called pozelimab and cemdisiran, and cemdisiran monotherapy. The study is focused on patients with generalized Myasthenia Gravis (gMG). Myasthenia gravis is a disease that causes weakness and fatigue in muscles in the body because the nerves and muscles are not communicating properly.
The aim of the study is to see how effective pozelimab and cemdisiran are when used in combination and when pozelimab and cemdisiran are used alone for patients with gMG.
The study is looking at several other research questions, including:
- What side effects may happen from taking the study drugs
- How the study drugs work inside the body
- How much of the study drugs are in the blood at different times
- Whether the body makes antibodies against pozelimab and cemdisiran (which could make the drugs less effective or could lead to side effects)
详细描述
DBTP- Double Blind Treatment Period (24 weeks) ETP - Extension Treatment Period (28 weeks) OLTP- Open Label Treatment Period (68 weeks) FUP-Off treatment Follow Up Period (52 weeks)
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female participants ≥18 years of age at screening (or ≥ legal age of adulthood based on local regulations, whichever is older)
- •Participant with documented diagnosis of Myasthenia Gravis (MG) based on medical history and supported by previous evaluations as described in the protocol
- •Documented prior history of positive serologic test or a positive result during screening of Anti-acetylcholine Receptor (AChR) antibodies or anti-Lipoprotein Receptor-related Protein 4 (LRP4) antibodies.
- •Myasthenia Gravis Foundation of America (MGFA) Clinical Classification Class II to IVa at screening
- •Myasthenia Gravis-Activities of Daily Living (MG-ADL) score ≥6 at screening. Ocular items should not contribute more than 50% of MG-ADL total score as described in the protocol
- •Currently receiving an acetylcholinesterase inhibitor or documented reason for not using acetylcholinesterase inhibitor therapy per investigator
- •Currently receiving an Immunosuppressive Therapy (IST) for MG, or documented reason why the participant is not taking an IST per investigator
- •If currently receiving an IST, not anticipated to have IST dosage changed before randomization or during Double-Blind Treatment Period (DBTP).
- •Willing and able to comply with clinic visits and study-related procedures, including completion of the primary series of the meningococcal vaccinations required per protocol
排除标准
- •Patients with antibody profile that is only positive for Muscle-Specific tyrosine Kinase (MuSK) (MuSK positivity is based on a documented prior history of positive serologic test for antibodies to MuSK or a positive result during screening
- •History of thymectomy within 12 months prior to screening or planned during the study
- •History of malignant thymoma (patients with stage 1 may be enrolled), or history of cancer within the past 5 years, except for adequately treated basal cell skin cancer, squamous cell skin cancer, or in situ cervical cancer
- •Myasthenic crisis or MGFA Class V within 1 month of screening
- •Not meeting meningococcal vaccination requirements and, at a minimum, documentation of quadrivalent meningococcal vaccination within 5 years prior to randomization and serotype B vaccine (when available) within 3 years prior to randomization as described in the protocol
- •Known contraindication to meningococcal vaccines (group ACWY conjugate and group B vaccines) as described in the protocol
- •Participants who require antibiotics for meningococcal prophylaxis and have a contraindication, warning, or precaution precluding the use of penicillin class and penicillin-alternative antibiotics planned to be used for prophylaxis, or a history of intolerance leading to the discontinuation of these antibiotics
- •Positive hepatitis B surface antigen or hepatitis C virus Ribonucleic Acid (RNA) during screening. NOTE: Cases with unclear interpretation should be discussed with the medical monitor
- •History of Human Immunodeficiency Virus (HIV) infection or a positive test at screening per local requirements
- •NOTE: Other protocol-defined Inclusion/ Exclusion Criteria apply
研究组 & 干预措施
Group 3
Cemdisiran throughout the study
干预措施: Cemdisiran (Drug)
Group 1
Placebo in DBTP; Re-randomized to Combination or Cemdisiran in ETP and OLTP
干预措施: Cemdisiran (Drug)
Group 4
Pozelimab monotherapy in DBTP followed by combination in ETP and OLTP. For participants who have not reached week 108 will receive cemdisiran monotherapy in the OLTP.
干预措施: Pozelimab (Drug)
Group 2
Combination regimen throughout the study. For participants who have not reached week 108 will receive cemdisiran monotherapy in the OLTP.
干预措施: Cemdisiran (Drug)
Group 4
Pozelimab monotherapy in DBTP followed by combination in ETP and OLTP. For participants who have not reached week 108 will receive cemdisiran monotherapy in the OLTP.
干预措施: Pozelimab + Cemdisiran (Drug)
Group 1
Placebo in DBTP; Re-randomized to Combination or Cemdisiran in ETP and OLTP
干预措施: Placebo (Other)
Group 1
Placebo in DBTP; Re-randomized to Combination or Cemdisiran in ETP and OLTP
干预措施: Pozelimab + Cemdisiran (Drug)
Group 2
Combination regimen throughout the study. For participants who have not reached week 108 will receive cemdisiran monotherapy in the OLTP.
干预措施: Pozelimab + Cemdisiran (Drug)
Group 4
Pozelimab monotherapy in DBTP followed by combination in ETP and OLTP. For participants who have not reached week 108 will receive cemdisiran monotherapy in the OLTP.
干预措施: Cemdisiran (Drug)
结局指标
主要结局
Change in Myasthenia Gravis-Activities of Daily Living (MG-ADL) total score
时间窗: From baseline to week 24
The total MG-ADL score ranges from 0 to 24 points, with higher scores indicating greater functional impairment and disability
次要结局
- Change from baseline in Quantitative Myasthenia Gravis (QMG) score(Week 24)
- Achievement of a ≥3-point reduction (improvement) in MG-ADL total score(From baseline to week 24)
- Achievement of a ≥5-point reduction (improvement) in QMG total score(From baseline to week 24)
- Change from baseline in the Myasthenia Gravis Composite (MGC) total score(Week 24)
- Achievement of a ≥2-, 4-, 5-, 6-, 7-, 8-, 9-, or 10-point reduction on MG-ADL total score(From baseline to week 24)
- Achievement of a ≥3-, 4-, 6-, 7-, 8-, 9-, or 10-point reduction on QMG(From baseline to week 24)
- Concentrations of total pozelimab in serum(Through study duration, approximate 172 weeks)
- Concentrations of cemdisiran and its metabolites in plasma(Through study duration, approximate 172 weeks)
- Incidence of treatment-emergent ADAs to cemdisiran over time(Through study duration, approximate 172 weeks)
- Change in total complement hemolysis activity assay (CH50) over time(Through study duration, approximately 172 weeks)
- Percent change in CH50 over time(Through study duration, approximately 172 weeks)
- Achievement of a consistent response on the MG-ADL(From baseline to week 24)
- Achievement of Minimal Symptom Expression (MSE)(Week 24)
- Change from baseline in Myasthenia Gravis Quality of Life (MG-QOL15r) total score(Week 24)
- Incidence and severity of Treatment-Emergent Adverse Events (TEAEs) in participants treated with pozelimab + cemdisiran, cemdisiran monotherapy or placebo(Through week 24)
- Incidence and severity of Serious Adverse Events (SAEs) in participants treated with pozelimab + cemdisiran, cemdisiran monotherapy or placebo(Through week 24)
- Incidence and severity of Adverse Events of Special Interest (AESIs) in participants treated with pozelimab + cemdisiran, cemdisiran monotherapy or placebo(Through week 24)
- Concentrations of total Complement component 5 (C5) in plasma(Through study duration, approximate 172 weeks)
- Incidence of treatment-emergent Anti-Drug Antibodies (ADAs) to pozelimab over time(Through study duration, approximately 172 weeks)