Single-arm, Open Label, Phase II Study of MBG453 (Sabatolimab) Added to FDA Approved Hypomethylating Agents of Investigator's Choice (IV/SC/Oral) for Patients With Intermediate, High or Very High Risk Myelodysplastic Syndrome (MDS) as Per IPSS-R Criteria (US Multi-center) (STIMULUS MDS-US)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 39
- 试验地点
- 15
- 主要终点
- Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events
研究概览
简要总结
The main objective of this study was to assess the safety profile of MBG453 (sabatolimab) in combination with FDA approved hypomethylating agents (HMAs) of investigator's choice (IV Decitabine or Azacitidine /SC Azacitidine /Oral Decitabine (cedazuridine combination (INQOVI))).
详细描述
This was a single arm, nonrandomized, open label, Phase II multicenter study of i.v sabatolimab added to FDA approved HMA agents of Investigator's choice (i.v/s.c/oral) in adult patients with intermediate, high or very high risk MDS as per IPSS-R criteria.
There were 4 separate periods of this study:
- Screening period (signing of written informed consent through day of enrollment),
- Core phase for up to 12 months,
- Extension phase for efficacy and/or survival status (up to 12 months after the core phase),
- Post-treatment safety follow-up period monitoring for AEs for 30 days following the last dose of azacitidine or decitabine or INQOVI (oral decitabine), or 150 days following the last dose of sabatolimab, whichever was later.
During the conduct of the study there were 2 updates to the Novartis development strategy for sabatolimab. Based on the results from the Phase II STIMULUS MDS-1 study, recruitment was halted for CMBG453B1US01 (STIMULUS MDS-US) on 30-Sep-2022. Novartis confirmed the decision to halt recruitment was not based on any safety findings or safety concerns. Patients who were on study treatment or in follow-up were continued as per the protocol. Furthermore, on 11-Jan-2024, all sabatolimab investigators were notified by Novartis that, based on decision taken in Dec-2023, that the sabatolimab development program (which included study CMBG453B1US01) would be terminated. After the decision was made to discontinue the sabatolimab development program, participants already enrolled in the CMBG453B1US01 study were prepared for closure; these close out activities took approximately 9 months. The actual last patient last visit date was 1 Sep 2024.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
MBG453 (sabatolimab) + HMA
MBG453 (sabatolimab) + HMA of investigator's choice (IV Decitabine or Azacitidine /SC Azacitidine /Oral Decitabine (cedazuridine combination (INQOVI)))
干预措施: INQOVI (oral decitabine) (Drug)
MBG453 (sabatolimab) + HMA
MBG453 (sabatolimab) + HMA of investigator's choice (IV Decitabine or Azacitidine /SC Azacitidine /Oral Decitabine (cedazuridine combination (INQOVI)))
干预措施: Decitabine (Drug)
MBG453 (sabatolimab) + HMA
MBG453 (sabatolimab) + HMA of investigator's choice (IV Decitabine or Azacitidine /SC Azacitidine /Oral Decitabine (cedazuridine combination (INQOVI)))
干预措施: Azacitidine (Drug)
MBG453 (sabatolimab) + HMA
MBG453 (sabatolimab) + HMA of investigator's choice (IV Decitabine or Azacitidine /SC Azacitidine /Oral Decitabine (cedazuridine combination (INQOVI)))
干预措施: MBG453 (Drug)
结局指标
主要结局
Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events
时间窗: Adverse events are reported from the first dose of study medication up to approximately 24 months plus 30 - 150 day safety follow up dependent on HMA, for a maximum timeframe of approximately 29 months.
An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a participant or clinical investigation participant after providing written informed consent for participation in the study. Therefore, an AE may or may not be temporally or causally associated with the use of a medicinal (investigational) product.
次要结局
- Number of Participants With Improvement in Packed RBCs Transfusion Independence - At Least One Period of Transfusion Independence Post Baseline(up to Month 24)
- Number of Participants With Complete Remission According to International Working Group (IWG) for MDS (2006) With MBG453 (Sabatolimab) in Combination With HMAs (IV/SC/Oral) by 12 Months.(up to Month 12)
- Number of Participants With Progression Free Survival - Death and Disease Progression(up to Month 24)
- Progression Free Survival - 50th Percentile(up to Month 24)
- Progression Free Survival - Percent Probability - Kaplan-Meier Probability Estimates(Months 6 and 12)
- Overall Survival - Number of Participants Who Died(up to Month 24)
- Overall Survival - 50th Percentile(up to Month 24)
- Overall Survival - Percent Probability - Kaplan-Meier Probability Estimates(up to Month 24)
- Leukemia-free Survival - Number of Participants Who Died and Number of Participants Who Progressed to Leukemia(up to Month 24)
- Leukemia-free Survival - 50th Percentile(up to Month 24)
- Leukemia-free Survival - Percent Probability - Kaplan-Meier Probability Estimates(Months 6 and 12)
- Percentage of Participants With Complete Remission, Marrow Complete Remission and/or Partial Remission(up to Month 24)
- Time to Complete Remission(up to Month 24)
- Improvement in Packed RBCs Transfusion Independence - Mean Total Duration (Weeks) of Transfusion Independence Post-baseline(up to Month 24)
- Improvement in Platelets Transfusion Independence - Mean Total Duration (Weeks) of Transfusion Independence Post-baseline(up to Month 24)
- Number of Participants With Improvement in Platelets Transfusion Independence - At Least One Period of Transfusion Independence Post Baseline(up to Month 24)