Intravenous Gammaglobulin for Sickle Cell Pain Crises

Albert Einstein College of Medicine300 enrolled

Overview

The purpose of this study is to determine whether Intravenous Immunoglobulin (IVIG) 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)

Patients will be randomized to a single dose of IVIG versus normal saline placebo during an uncomplicated pain crisis. Length of vaso-occlusive crisis (VOC) and other secondary endpoints will be monitored. Phase I: 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, ages 12-65, admitted for acute vaso-occlusive crisis. Phase II: To evaluate the effect of a single dose of 400mg/kg of intravenous (IV) Gamunex on length of VOC in subjects 6-13.99 years of age (initially 8-65 years of age, see "NOTES/CLARIFICATION below) hospitalized for sickle cell VOC in a randomized, double blind placebo-controlled Phase II trial. To further evaluate safety of a single dose of 400mg/kg of IV Gamunex in subjects 6-65 years of age hospitalized for sickle cell VOC. NOTES/CLARIFICATION: The following is a timeline of the 'evolution' of the required Age Range as per eligibility criteria for this study: Initial Age Range: 8-65 years of age Effective 1/2/2013: 12-65 years of age Effective 3/31/2015: 8-21 years of age Effective 6/22/2018: 8-13 years of age Effective 7/11/2019: 6-13.99 years of age

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

300

Conditions

Sickle Cell Disease Pain

Interventions

Immune Globulin Intravenous (IVIG)DRUG

A single dose of intravenous immune globulin administered within 24 hours of hospital presentation. The maximum dose in Phase I was 800 mg/kg. The dose for Phase II is 400mg/kg.

Normal salineOTHER

A single dose of normal saline administered within 24 hours of hospital admission for uncomplicated pain crisis.

Eligibility

Sex: ALLMin age: 6 YearsMax age: 13 Years

Medical Language ↔ Plain English

Each subject must fulfill each of the following Inclusion/Exclusion criteria at screening and continue to fulfill these criteria prior to dosing: Inclusion Criteria: * 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 Exclusion Criteria: * 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)

Locations (1)

Montefiore Medical Center

The Bronx, New York, United States

Outcomes

Primary Outcomes

Length of vaso-occlusive crisis (VOC)

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.

Time frame: Number of days from time of presentation to emergency room to end of crisis, average 4 days and maximum 30 days

Secondary Outcomes

Total Opioid Use

The total intravenous morphine equivalent use from the end of infusion to discharge will be compared between the IVIG and placebo group. This will require conversion of total amount of different opioids to the equivalent amounts of IV morphine in milligrams. Standard tables for equianalgesic opioid dosing will be used for these conversions. These tables account for opioid type, route of administration, and incomplete cross-tolerance, as needed, and are adjusted for body weight. Group results will be summarized in milligrams of opioid per kilogram of body weight (mg/kg) using univariate statistics.

Time frame: From study drug infusion to end of crisis, average 4 days and maximum 30 days

Time to end of vaso-occlusive crisis

Time to end of vaso-occlusive crisis as measured from start of study drug infusion to end of VOC 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.

Time frame: Number of days from start of study drug infusion to end of crisis, average 4 days and maximum 30 days

Length of Hospitalization

Length (duration) of Hospitalization will be summarized by study arm in months/days using univariate statistics.

Time frame: From admission to discharge, average 4 days and maximum 30 days

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.