Open-label, Long-term, Extension Treatment Using Intra-Erythrocyte Dexamethasone Sodium Phosphate (EryDex System) in Patients With Ataxia Telangiectasia Who Participated in the ATTeST-IEDAT-02-2015 Study
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 104
- 试验地点
- 29
- 主要终点
- Number of Treatment-Emergent Adverse Event (TEAE), Treatment-emergent Serious Adverse Events (TESAE), and Adverse Events of Special Interest (AESI) Throughout the Study
研究概览
简要总结
Primary Objective
To monitor and evaluate the long-term safety and tolerability of EDS-EP in AT patients.
Secondary Objective
To evaluate the long-term effect of EDS-EP on health-related Quality of Life (QoL; EQ-5D-5L scale).
Exploratory Objective:
To evaluate the long-term effect of EDS-EP in treating central nervous system (CNS) symptoms, as measured by the "Modified" International Cooperative Ataxia Rating Scale (mICARS), and Clinical Global Impression of severity and change (CGI-S/C).
详细描述
This was an international (North America, Europe, Africa, Asia and Australia), multi-center, prospective, open-label treatment study, designed to continue to provide the study medication to all patients who completed 12 months of treatment (including those treated with placebo) in the ATTeST-IEDAT-02-2015 trial, completed the study assessments, do not present safety contraindication to continuation of treatment, and provided informed consent.
The study aimed to collect information on the long-term safety and efficacy of the trial treatment.
Patients meeting all selection criteria received monthly infusions of EDS-EP (dose range of ~14-22 mg DSP/infusion). If this dose of EDS-EP was not tolerated, the patient was discontinued from the study.
During the study, long-term efficacy assessments were performed every 6 months, while safety parameters were assessed at each monthly visit. The Schedule of Visits and assessments for the first 12 months were replicated for the second year onwards for patients who continued EryDex treatment beyond 12 months.
The analysis of the EryDex long-term safety and tolerability was based on the occurrence of Treatment-Emergent Adverse Events (TEAEs), including Serious AEs and discontinuations due to AEs. The long-term effect was measured by the "Modified" International Cooperative Ataxia Rating Scale, (mICARS), Rescored mICARS, Clinical Global Impression of severity and change (CGI-S/C) and health-related Quality of Life (QoL; EQ-5D-5L scale).
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
盲法说明
It's a open label extension study, so no blinding was applicable.
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
- •Patient completed the double-blind period in the ATTeST study and completed the final (Visit 15 / Month 12) Efficacy Assessments of ATTeST or discontinued the study during the COVID-19 pandemic.
- •Patient tolerated the study medication, without any evidence of steroid adverse events, or treatment-related severe events / serious adverse events.
- •Body weight > 15 kg.
- •The patient and his / her parent / caregiver (if below the age of consent), or a legal representative, provided written informed consent to participate. If consent was provided solely by the caregiver in accordance with local regulations, the patient also was asked to provide their assent to participate in the study.
- •Patient did not present safety contraindication for continuation of treatment, as determined by the Principal Investigator (PI) according to the procedures described below.
- •Moreover, patients who were discontinued from the ATTeST study during the COVID-19 pandemic were eligible to receive the EryDex treatment in the IEDAT-03-2018 study, in the absence of safety contraindications to continuation of the treatment, and after signing the informed consent.
- •There were no de novo enrolled patients.
排除标准
- •Patients who met one or more of the following criteria were not considered to be eligible to participate in the study:
- •Females that were:
- •Pregnant, or were breast-feeding (for EU countries only)
- •Of childbearing potential, pregnant, or were breast-feeding (for US and Rest of World countries).
- •Females of childbearing potential using adequate birth control, as determined by their Health Care Provider, were eligible.
- •A disability that may prevent the patient from completing all study requirements.
- •Current participation in another clinical study with another investigational drug.
- •Medical History and Current Status
- •Cluster differential 4 positive (CD4+) lymphocytes count < 400 / mm3 (for patients 6 years of age) or < 150 / mm3 (for patients > 6 years). In presence of oral infections, like oral candidiasis, documented at the screening or recurrent as per medical history documentation, the limit increases to < 200 / mm3 (for patients > 6 years).
- •Current neoplastic disease.
- •Severe impairment of the immunological system.
- •Severe or unstable pulmonary disease.
- •Uncontrolled diabetes. Patients with diabetes that had been stabilized (i.e., no hypoglycemic or hyperglycemic episodes in the past 3 months) were eligible.
- •Any other severe, unstable, or serious disease or condition that in the Investigator's opinion would put the patient at risk for imminent life-threatening morbidity, need for hospitalization, or mortality.
- •Eligibility of patients with abnormal laboratory test values were determined by the Investigator.
- •Confirmed haemoglobinopathies, e.g., haemoglobin C disease, sickle cell anaemia, or thalassemia.
- •Moderate or severe renal and / or hepatic impairment.
- •Patients who experienced moderate / severe steroid side effects, or moderate / severe adverse events associated with the EryDex treatment administered in the ATTeST study.
- •Prior / Concomitant Medication
- •Requires treatment with an oral or parenteral steroid. Treatment with inhaled or intranasal steroids for asthma or allergies, as well as use of topical steroids were permitted.
- •Requires any other concomitant medication prohibited by the protocol.
- •Use of any drug that is a strong inducer / inhibitor of Cytochrome P450 3A4 (CYP3A4).
结局指标
主要结局
Number of Treatment-Emergent Adverse Event (TEAE), Treatment-emergent Serious Adverse Events (TESAE), and Adverse Events of Special Interest (AESI) Throughout the Study
时间窗: From Baseline (Visit 1 - Day 0) to Follow-up (~60 days after last infusion, i.e. up to 50.5 months)
Assessment of TEAEs, treatment-emergent serious adverse events (TESAE), and adverse events of special interest (AESI) were performed throughout the study, from the time of signing of the ICF at Baseline Visit through to the Final Study Visit (Month 12 or early discontinuation). All patients were to be followed up through 30 days after the Final Visit (Month 12 or early discontinuation) or at least 60 days after the final infusion, whichever was longer.
次要结局
- Change From Baseline in Quality of Life Using EQ-5D-5L Scale to Month 36(From Baseline (Visit 1- Day 0) to Month 36)
- Number of Patients With Improving, Stable or Worsening Score Using a Clinical Global Impression of Change (CGI-C) From Baseline (Visit 1- Day 0) to Month 36(From Baseline (Visit 1- Day 0) to Month 36)
- Number of Patients With None to Severe (0 to 4) Scores in Clinical Global Impression of Severity (CGI-S)-Structured of Neurological Symptoms of AT From Baseline (Visit 1 - Day 0) to Month 36(From Baseline (Visit 1- Day 0) to Month 36)
- Change From Baseline of the Modified International Cooperative Ataxia Rating Scale (mICARS) Until Month 36(From Baseline (Visit 1- Day 0) to Month 36)