A Phase 2a, Randomized, Open-Label Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ISIS 702843 Administered Subcutaneously to Patients With Non-Transfusion Dependent β-Thalassemia Intermedia
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 29
- 试验地点
- 19
- 主要终点
- Percentage of Participants With a ≥1.0 Grams Per Deciliter (g/dL) Increase From Baseline in Hemoglobin (Hb) at Week 27
研究概览
简要总结
The purpose was to evaluate the efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics of sapablursen administered subcutaneously to participants with non-transfusion dependent β-Thalassemia Intermedia.
详细描述
This was a multi-center, randomized, open-label study in up to 29 participants. The duration of participation for each subject in the study was approximately 29 months and included an approximately 2-month screening period, a 24-month treatment period, and a 3-month post-treatment period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Willingness to comply with study procedures
- •Clinical diagnosis of Beta-Thalassemia Intermedia with genotypic confirmation
- •Non-transfusion dependent, as defined by: no more than 6 transfusions in the past 12-month period, and no transfusions in the 8-week period prior to Day 1
- •Mean Hb within the range of 6.0-10.0 g/dL, inclusive at Screening
- •LIC within the range of 3.0-20.0 mg Fe/g dry weight, inclusive
- •If using chelators, must be on a stable dose for at least 3 months with liver iron concentration (LIC) > 5.0 mg iron (Fe) per gram of dry weight of liver (Fe/g) dry weight and serum ferritin > 300 nanograms per milliliter (ng/mL)
- •Females must be non-pregnant and non-lactating, and either surgically sterile or postmenopausal
- •Males must be surgically sterile, abstinent or using an acceptable contraceptive method
排除标准
- •Clinically significant abnormalities in lab values, medical history, or physical examination
- •α-globin gene triplication
- •Symptomatic splenomegaly
- •Platelet count < lower limit of normal (LLN) or > 1,000 x 10^9/L
- •Significant concurrent/recent coagulopathy, history of non-traumatic significant bleeding; history of immune thrombocytopenic purpura (ITP); current use of SC anti-coagulants; history of thrombotic events, including stroke or DVT
- •Clinically significant renal, liver or cardiac dysfunction
- •Uncontrolled hypertension (> 140 mm Hg systolic or > 90 mm Hg diastolic)
- •Fasting blood glucose > 2.0 × upper limit of normal (ULN)
- •Inability to have a magnetic resonance imaging (MRI) scan
- •Known history or positive test for human immunodeficiency virus (HIV), hepatitis C (HCV), or hepatitis B (HBV)
- •Active infection requiring systemic antiviral or antimicrobial therapy
- •Regular excessive use of alcohol
- •Recent start of hydroxyurea (6 months prior to Day 1)
- •Treatment with or recent exposure to another investigational drug, biological agent, antisense oligonucleotide (ASO), small interfering ribonucleic acid (siRNA), or device within 1 month of Screening, or 5 half-lives of investigational agent, whichever is longer; or treatment with or exposure to:
- •sotatercept (ACE-011), luspatercept (ACE-536), or ruxolitinib within 4 months of Screening
- •hematopoietic stimulating agents or any hypoxia-inducible factor prolyl hydroxylase inhibitors within 8 weeks of Day 1
- •prior bone marrow transplant, stem cell transplant, or gene therapy
- •Surgery associated with significant blood loss within 4 months of Screening, splenectomy within 12 months of Screening, or splenectomy scheduled during treatment
研究组 & 干预措施
Cohort A: Sapablursen
Subjects initially received 30 mg/0.3 mL of sapablursen by (subcutaneous) SC injection once every four weeks up to Week 105. After the protocol Amendment 2 the dose was increased to a maximum of 160 mg once every 4 weeks.
干预措施: sapablursen (Drug)
Cohort B: Sapablursen
Subjects initially received 50 mg/0.5 mL of sapablursen by SC injection once every four weeks up to Week 105. After the protocol Amendment 2 the dose was increased to a maximum of 160 mg once every 4 weeks
干预措施: sapablursen (Drug)
Cohort C: Sapablursen
Subjects initially received 80 mg/0.8 mL of sapablursen by SC injection once every four weeks up to Week 105. After the protocol Amendment 2 the dose was increased to a maximum of 160 mg once every 4 weeks.
干预措施: sapablursen (Drug)
结局指标
主要结局
Percentage of Participants With a ≥1.0 Grams Per Deciliter (g/dL) Increase From Baseline in Hemoglobin (Hb) at Week 27
时间窗: Baseline and Week 27
Blood hemoglobin
次要结局
- Percentage of Participants With a ≥1.5 g/dL Increase From Baseline in Hb at Week 53(Week 53)
- Percentage of Participants With a ≥1.0 Milligrams of Iron Per Grams of Dry Weight of Liver (mg Fe/g) Decrease From Baseline in Liver Iron Concentration (LIC) at Week 53(Week 53)