Phase 1-2 Trial of Gamunex (Intravenous Gammaglobulin) for Sickle Cell Acute Pain
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- Length of vaso-occlusive crisis (VOC)
研究概览
简要总结
The purpose of this study is to determine whether intravenous immune globulin is safe and effective in the acute treatment of pain crises in sickle cell disease.
Funding Source: Food and Drug Administration (FDA), Office of Orphan Products Development (OOPD)
详细描述
Patients will be randomized to a single dose of IVIG versus normal saline placebo during an uncomplicated pain crisis. Length of VOC and other secondary endpoints will be monitored.
Phase 1: To determine the tolerability and obtain preliminary data on the clinical efficacy of IVIG treatment in a randomized, double-blind, placebo-controlled, dose escalation phase I clinical study of sickle cell disease patients admitted for acute vaso-occlusive crisis.
Phase II: To evaluate the effect of a single dose of 400mg/kg of IV Gamunex on length of VOC in subjects 8-14 years of age hospitalized for sickle cell VOC in a randomized, double blind placebo-controlled Phase 2 trial. To further evaluate safety of a single dose of 400mg/kg of IV Gamunex in subjects 8-14 years of age hospitalized for sickle cell VOC
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)
入排标准
- 年龄范围
- 6 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented Sickle Cell Disease (SS or S-β thalassemia genotype)
- •Age 12-65 years for Phase 1 (Completed), 6-13.99 years for Phase 2 (Ongoing)
- •Normal stroke risk as assessed by transcranial Doppler (TCD). A normal TCD in subjects 16 years of age and younger within the year prior to study drug administration are required
- •Uncomplicated acute vaso-occlusive crisis requiring hospital admission and parenteral narcotic analgesics
- •If prescribed Voxelotor: Consistent daily use of voxelotor in the past week AND able to continue Voxelotor inpatient OR no reported use in prior week
排除标准
- •Concomitant acute process, including acute chest syndrome, potential serious infection, or clinically significant bleeding
- •Fever > 38.5° C and clinical suspicion of infection
- •Serum alanine aminotransferase >4x Upper Limit of Normal (ULN)
- •Serum creatinine ≥1.3 mg/dL (or > than 95th percentile for age) or >300 mg/dL protein in spot urinalysis
- •Known condition associated with renal dysfunction including but not limited to diabetes mellitus, uncontrolled hypertension, multiple myeloma, and congestive heart failure
- •Any clinical evidence of prior stroke
- •Prior thromboses or current estrogen use
- •Current estrogen use
- •Hb < 5 g/dL or > 10 g/dL
- •Known Immunoglobulin A (IgA) deficiency or known allergy to gamma globulin
- •Pregnancy or breastfeeding
- •Current participation in another investigational drug study
- •Current enrollment in a hypertransfusion program
- •Previous participation in current study less than 3 months ago
- •Current treatment with chronic transfusion
- •Vaccination with a live attenuated virus in the preceding 6 weeks
- •Documented history of illicit (e.g., heroin, cocaine) drug abuse
- •Subject is otherwise not an appropriate study candidate, in the investigator's judgement, such as concern for opioid addiction or comorbid psychiatric diagnoses that may contribute to secondary gain in prolonged use of opioids or hospital stay
- •Greater than 24 hours from time of presentation to the hospital for VOC
- •Atrial fibrillation
- •Right to left cardiac shunting due to patent foramen ovale or other anatomic cause
- •Known magnetic resonance imaging/angiography (MRI/A) evidence of stroke or clinically significant central nervous system (CNS) vasculopathy at any age (Imaging done if clinically indicated)
研究组 & 干预措施
Intravenous Immune Globulin (IVIG)
IVIG used in the trial is the GAMUNEX brand, at doses up through 800 mg/kg in Phase 1 and at 400mg/kg in Phase 2.
干预措施: Immune Globulin Intravenous (IVIG) (Drug)
Normal saline
An equivalent volume (weight-based) of normal saline
干预措施: Normal saline (Other)
结局指标
主要结局
Length of vaso-occlusive crisis (VOC)
时间窗: Number of days from time of presentation to emergency room to end of crisis, average 4 days and maximum 30 days
Length (duration) of vaso-occlusive crisis as measured from the time of presentation to the emergency room to end of VOC defined as 12 hours from the last dose of parenteral opioid analgesia for the treatment of VOC prior to hospital discharge. Group results will be summarized in number of days using univariate statistics.
次要结局
- Total Opioid Use(From study drug infusion to end of crisis, average 4 days and maximum 30 days)
- Time to end of vaso-occlusive crisis(Number of days from start of study drug infusion to end of crisis, average 4 days and maximum 30 days)
- Length of Hospitalization(From admission to discharge, average 4 days and maximum 30 days)
- Change in Macrophage-1 Antigen (Mac-1) expression(From Pre-infusion to 24-hours post-infusion)
- Change in Lactate Dehydrogenase (LDH) levels(From Pre-infusion to 24-hours post-infusion)
- Change in Hemoglobin (Hb) levels(From Pre-infusion to 24-hours post-infusion)
- Change in High-sensitivity C-reactive protein (hsCRP) levels(From admission to 24-hours post-infusion, average 4 days)
- Rate of transfer to Intensive Care Unit (ICU)(From admission to discharge, average 4 days and maximum 30 days)
- Diagnosis leading to transfer to the ICU(From admission to discharge, average 4 days and maximum 30 days)
- Number and type of Transfusions(From study drug infusion to discharge, average 4 days and maximum 30 days)