Intravenous Gammaglobulin for Sickle Cell Pain Crises

Study Overview
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Brief Summary
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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)

Detailed Description
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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.

Official Title
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Phase 1-2 Trial of Gamunex (Intravenous Gammaglobulin) for Sickle Cell Acute Pain

Conditions
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Sickle Cell Disease, Pain

Intervention / Treatment
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* Drug: Immune Globulin Intravenous
* Other: Normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented diagnosis of 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) Uncomplicated acute pain episode requiring hospital admission and parenteral narcotics Exclusion Criteria: Increased stroke risk as assessed by transcranial Doppler or magnetic resonance imaging (all subjects undergo testing) Concomitant acute process, including fever > 38.5° C with clinical suspicion of infection Increased ALT > 2X ULN Serum creatinine ≥1.3 mg/dL, >300 mg/dL protein in spot urinalysis, or known condition associated with renal dysfunction Hb > 10 g/dL and Hct > 30% Hb< 5 g/dl Known IgA deficiency or known allergy to gamma globulin Pregnancy or breastfeeding Vaccination with a live attenuated virus in the preceding 6 weeks Documented history of illicit (eg. heroin, cocaine) drug abuse or drug-seeking behavior Current participation in another investigational drug study Current treatment with chronic transfusion Prior thromboses or current estrogen use

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Immune Globulin Intravenous<br>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. | Drug: Immune Globulin Intravenous<br>* A single dose of intravenous immune globulin or saline placebo 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.<br>* Other names: GAMUNEX (Talecris Biotherapeutics);|
| Placebo Comparator: Normal saline<br>An equivalent volume (weight-based)of normal saline | Other: Normal saline<br>* A single dose of normal saline administered within 24 hours of hospital admission for uncomplicated pain crisis.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of vaso-occlusive crisis | Length 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. | Number of days from time of presentation to emergency room to end of crisis, average 4 days and maximum 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total opioid use in equivalent of mg of IV morphine | 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 | 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 | Number of days from start of study drug infusion to end of crisis, average 4 days and maximum 30 days | 
| In vitro adhesion assays | Activated Mac-1, Aged neutrophils | Pre and 24 hours post study drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sickle Cell Disease, Pain, Immune Globulin