A Prospective, Observational Study Evaluating the Real-World Experience of Givinostat in Patients With Duchenne Muscular Dystrophy
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 300
- 试验地点
- 11
- 主要终点
- Characterize the incidence of thrombocytopenia / decreased platelet counts in DMD patients treated with oral givinostat
研究概览
简要总结
This is a prospective observational study conducted to evaluate safety, tolerability, and functional outcomes of patients with DMD newly initiating oral givinostat or having started therapy within 6 months as part of routine clinical care in the US. The study has a planned maximum duration of 5 years for the first enrolled patients, including a 24-month enrollment period and a minimum of 2 years of follow-up.
详细描述
Duchenne Muscular Dystrophy (DMD) is a rare genetic disorder that leads to progressive muscle degeneration and weakness. Givinostat, an oral histone deacetylase inhibitor, was approved by the FDA in March 2024 for treatment of DMD in patients aged 6 years and older, regardless of mutation type.
Study participation will not influence the course of treatment in any way (including other treatments for DMD), and no treatment will be provided as part of this study. All assessments are intended to be performed at the time of a routine clinical care visit according to clinical practice, and data will be extracted from the medical records.
The FDA is requiring a post-marketing prospective study be conducted for a minimum of 5 years to characterize the incidence, frequency, and severity of thrombocytopenia and serious events of bleeding in patients with DMD treated with oral givinostat in routine clinical practice.
This study is designed as a prospective, observational study to assess safety (including evaluation of AEs of special interest [AESIs]) and effectiveness, in patients with DMD newly initiating oral givinostat as part of routine clinical care in the US in a real-world population. The study will assess AESIs noted above, as well as serious adverse events (SAEs), gastrointestinal (GI) AEs, and dehydration as a sequela to GI AEs. Real-world-treatment patterns of DMD treatments (corticosteroids, exon skipping oligonucleotides and gene therapy) prior to and after givinostat initiation, including treatment duration, and treatment combinations, will be described. Effectiveness evaluations will characterize motor function, quality of life, and activities of daily living in DMD patients treated with givinostat.
The study will enroll 300 participants (180 non-ambulatory and up to 120 ambulatory patients). Participants will be followed for at least two years, with data collected during routine clinical visits. Assessments include lab parameters (e.g., platelet counts, triglycerides), cardiac and pulmonary function, patient-reported outcomes, and motor function scales such as the North Star Ambulatory Assessment (NSAA) and Performance of Upper Limb (PUL) scale.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 6 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients of any gender at least 6 years of age, diagnosed with DMD (according to genetic test) and have received a prescription for oral givinostat in accordance with the USPI.
- •Patient has provided informed consent (and assent when applicable) for participation in the study.
- •Patient's index date (first date of givinostat treatment) is no more than 6 months prior to signing of informed consent.
- •Patient has the required data available (DMD diagnosis, givinostat administration [dose and schedule], laboratory results [hematology and triglycerides]) for addressing the study objectives for the period between index date and study entry (for patients enrolled after the index date).
排除标准
- •Patient previously received givinostat (commercial or investigational product) and permanently discontinued treatment or patient started commercial givinostat for > 6 months before signing of informed consent.
研究组 & 干预措施
Non-Ambulatory
Non-ambulatory status is determined by inability to perform the 10mWR test as defined above.
This cohort will include approximately 180 patients who are non-ambulatory prior to starting givinostat.
Ambulatory
Ambulatory is defined as being able to complete the 10-meter Walk-Run (10mWR) test within 30 seconds without an assistive device.
This cohort will include up to 120 patients who are ambulatory prior to starting givinostat treatment.
Within this cohort , 95 patients must have had prior use or a referral for concomitant use of dystrophin-enhancing therapy (DET), such as exon skipping oligonucleotides or gene therapy.
Enrollment is capped at 25 patients without prior or referred DET use.
结局指标
主要结局
Characterize the incidence of thrombocytopenia / decreased platelet counts in DMD patients treated with oral givinostat
时间窗: From follow up (after first date of givinostat treatment) through end of study (up to 5 years)
Incidence rate of thrombocytopenia (per 100 patient years of observation time) post index date
Characterize the frequency of thrombocytopenia / decreased platelet counts in DMD patients treated with oral givinostat
时间窗: [Time Frame: From follow up (after first date of givinostat treatment) through end of study (up to 5 years)]
Frequency and incidence proportion (overall and by maximum severity) of thrombocytopenia
Characterize the incidence of serious events of bleeding in DMD patients treated with oral givinostat
时间窗: From follow up (after first date of givinostat treatment) through end of study (up to 5 years)
Incidence rate of serious bleeding events (per 100-patient years of observation time) post index date
Characterize severity of serious events thrombocytopenia / decreased platelet counts in DMD patients treated with oral givinostat
时间窗: From follow up (after first date of givinostat treatment) through end of study (up to 5 years)
Time to first thrombocytopenia event from index date
Characterize the frequency of serious events of bleeding in DMD patients treated with oral givinostat
时间窗: From follow up (after first date of givinostat treatment) through end of study (up to 5 years)
Frequency and incidence proportion (overall and by maximum severity) of serious bleeding events
Characterize the severity of serious events of bleeding in DMD patients treated with oral givinostat
时间窗: From follow up (after first date of givinostat treatment) through end of study (up to 5 years)
Time to first serious bleeding event from index date
次要结局
- Characterize the severity of gastrointestinal (GI) AEs (nausea, vomiting, diarrhea, abdominal pain, constipation) in DMD patients treated with givinostat(From follow up (after first date of givinostat treatment) through end of study (up to 5 years))
- Characterize the frequency other adverse events of special interest (AESIs) in DMD patients treated with oral givinostat(From follow up (after first date of givinostat treatment) through end of study (up to 5 years))
- Characterize the severity of other adverse events of special interest (AESIs) in DMD patients treated with oral givinostat(From follow up (after first date of givinostat treatment) through end of study (up to 5 years))
- Characterize the incidence of all serious adverse events (SAEs) in DMD patients treated with oral givinostat(From follow up (after first date of givinostat treatment) through end of study (up to 5 years))
- Characterize the incidence of other adverse events of special interest (AESIs) in DMD patients treated with oral givinostat(From follow up (after first date of givinostat treatment) through end of study (up to 5 years))
- Characterize the frequency of all serious adverse events (SAEs) in DMD patients treated with oral givinostat(From follow up (after first date of givinostat treatment) through end of study (up to 5 years))
- Characterization of hematology laboratory parameters(From baseline through end of study (up to 5 years))
- Characterize the incidence of gastrointestinal (GI) AEs (nausea, vomiting, diarrhea, abdominal pain, constipation) in DMD patients treated with givinostat(From follow up (after first date of givinostat treatment) through end of study (up to 5 years))
- Characterize the frequency of gastrointestinal (GI) AEs (nausea, vomiting, diarrhea, abdominal pain, constipation) in DMD patients treated with givinostat(From follow up (after first date of givinostat treatment) through end of study (up to 5 years))
- Characterization of triglyceride laboratory parameters(From baseline through end of study (up to 5 years))