A Randomized, Double-blind, Placebo-controlled Phase III Study to Evaluate the Efficacy, Safety, and Tolerability of Iptacopan in Patients With Generalized Myasthenia Gravis, Followed by an Open-label Extension Phase
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 146
- 试验地点
- 248
- 主要终点
- Change from baseline to Month 6 in Myasthenia Gravis Activity of Daily Living (MG-ADL) total score
研究概览
简要总结
The study is a randomized, double-blind, placebo-controlled, multicenter, Phase III study, to evaluate efficacy, safety and tolerability of iptacopan in patients with AChR+ gMG who are on stable SOC treatment. Participants who meet the eligibility criteria will be randomized in a ratio of 1:1, to receive either iptacopan or matching placebo, for 6 months (180 days) while continuing on a stable SOC treatment. The randomization will be stratified based on region.
详细描述
The study consists of a 6-month double-blind treatment period for the primary efficacy and safety analysis followed by a maximum duration of 60 month open label extension period. A safety follow up assessment will be performed, one 7 days after the last administration of study treatment and one 30 days after the last administration of study treatment for all participants.
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)
盲法说明
This is a participant, investigator, and sponsor-blinded study. Participants, investigator staff, persons performing the assessments and the Clinical Trial Team will remain blinded to the identity of treatment from the time of randomization until database lock after all participants have completed the double-blind treatment period. The following methods will be used to ensure that blinding is properly maintained:
- Randomization data are kept strictly confidential until the time of unblinding and will not be accessible by anyone involved in the study
- The identity of the treatment will be concealed by the use of study treatments that are all identical in packaging, labeling, schedule of administration, appearance, taste, and odor
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients with generalized Myasthenia Gravis (age 18-85 years) at screening
- •Positive serology testing for AChR+ antibody at screening
- •Myasthenia Gravis Foundation of America (MGFA) Class II-IV gMG at screening and likely not in need of a respirator for the duration of the study, as judged by the Investigator.
- •The confirmation of the diagnosis of gMG should be documented and supported by ≥1 of the following 3 tests:
- •History of abnormal neuromuscular transmission demonstrated by single-fiber electromyography or repetitive nerve stimulation.
- •History of positive test with short-acting acetylcholinesterase inhibitors (e.g. neostigmine or edrophonium chloride)
- •Patient has demonstrated improvement in MG signs on oral acetylcholinesterase inhibitors as assessed by the treating physician.
- •Baseline MG-ADL score ≥6, with ≥50% of the total score due to non-ocular symptoms
- •Participants receiving at least one of the following treatments for gMG for ≥ 6 months prior to baseline;
- •One or more NSISTs or
- •plasmapheresis, plasma exchange, or intravenous immunoglobulin (at least quarterly) to control symptoms despite treatment with steroids and NSISTs; or
- •an approved FcRN antagonist approved for gMG; or
- •rituximab or
- •other approved gMG disease modifying therapies excluding complement inhibitors.
- •Vaccination against Neisseria meningitidis and Streptococcus pneumoniae infection is required prior to the start of study treatment. If the participant has not been previously vaccinated, or if a booster was required, the vaccine should be given according to local guidelines at least 2 weeks prior to first study drug administration. If study treatment has to start earlier than 2 weeks post-vaccination, prophylactic antibiotic treatment should be initiated at the start of study treatment and continued until at least 2 weeks after vaccination or booster was completed.
- •Note: For US sites participating in Study CLNP023Q12301, the completion of the meningococcal vaccination or booster is required for patients with gMG prior to initiating study treatment, irrespective of prophylactic antibiotic use.
排除标准
- •Have been treated with intravenous immunoglobulin (IVIG)/plasma exchange (PLEX) in the past month, with rituximab in the past 6 months, eculizumab in the past 2 months, ravulizumab or other complement inhibitors in the past 3 months, efgartigimod or other anti- FcRn therapies in the past 3 months, or had a thymectomy in the past 6 months or a planned thymectomy during the trial period.
- •Participants with clinically significant active or chronic uncontrolled bacterial, viral, or fungal infection at screening, including patients who test positive for an active viral infection at screening with: Active Hepatitis B Virus (HBV); Active Hepatitis C Virus (HCV);
- •Human Immunodeficiency Virus (HIV) positive serology associated with an Acquired Immune Deficiency Syndrome (AIDS)-defining condition or with a cluster of differentiation 4 (CD4) count
- •200 cells/mm3
- •Female participants who are pregnant or lactating, or are intending to become pregnant.
- •Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant from menarche until becoming post-menopausal, unless they are using effective methods of contraception during dosing of study treatment and an additional one week following cessation of study treatment. Women are considered post-menopausal if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., hormonal profile confirming menopause and/or age-appropriate history of vasomotor symptoms).
- •Active systemic bacterial, viral (including COVID-19) or fungal infection or any major episode of infection that required hospitalization or injectable antimicrobial therapy within 14 days prior to study drug administration.
- •History of recurrent invasive infections caused by encapsulated organisms, e.g., N. meningitidis and S. pneumoniae.
- •Presence of fever ≥ 38 °C (100.4 °F) within 7 days prior to study drug administration
研究组 & 干预措施
Matching Placebo
Placebo orally for 6 months (double-blind) followed by open-label iptacopan for up to 60 months
干预措施: Matching Placebo (Other)
Iptacopan
Iptacopan orally for 6 months (double-blind) followed by open-label iptacopan for up to 60 months
干预措施: Iptacopan (Drug)
结局指标
主要结局
Change from baseline to Month 6 in Myasthenia Gravis Activity of Daily Living (MG-ADL) total score
时间窗: Baseline to Month 6
The MG-ADL is an 8 item interviewer led patient reporting scale that assesses MG symptoms and their effects on daily activities. MG-ADL is composed of items related to patient's assessment of functional disability secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb (2 items) impairment related to effects from MG. Each item is assessed on a 4-points scale where a score 0 represents normal function and a score 3 represents loss of ability to perform that function. The scores ranges from 0 to 24, with a higher score indicating more disability.
次要结局
- Change from baseline to Month 6 in Quantitative MG (QMG) total score(Baseline to Month 6)
- Change from baseline to Month 6 in Myasthenia Gravis Composite (MGC) total score(Baseline to Month 6)
- Change from baseline to Month 6 in revised MG Quality of Life Questionnaire (MG-QOL15r) survey score(Baseline to Month 6)
- Incidence of adverse events(Baseline to Month 30 (end of extension phase))
- Proportion of early MG-ADL responders during treatment (early responders with first MG-ADL improvement from baseline of ≥ 2 points occurring by week 4）(Baseline to Month 6)
- Change from baseline to Month 6 in EuroQol-5 Dimensions-5 Level (EQ-5D-5L)(Baseline to Month 6)
- Incidence of adverse events(Baseline to Month 6)
- Proportion of participants with ≥ 5 points reduction from baseline to Month 6 of QMG total score without rescue medication and/or strongly confounding prohibited medication(Baseline to Month 6)
- Proportion of participants with ≥ 3 points reduction from baseline to Month 6 of MG-ADL total score without rescue medication and/or strongly confounding prohibited medication(Baseline to Month 6)
- Proportion of participants achieving MSE at Month 6, defined as MG-ADL score of 0 or 1 at Month 6 without rescue therapy and/or strongly confounding prohibited medication(Baseline to Month 6)
- Proportion of time during which participants showed a reduction of ≥ 2 points in MG-ADL total score that was maintained up to Month 6(Baseline to Month 6)
- Proportion of participants with a reduction of ≥ 3 points from baseline to Month 6 in MGC total score(Baseline to month 6)
- Change from baseline in MG-ADL total score(Baseline to Month 66 (end of extension phase))
- Proportion of participants achieving a reduction in oral corticosteroids (OCS) dose compared to Core Part that was maintained up to end of Extension Part(Month 6 (end of core phase) to Month 30 (end of extension phase))