Intravenous Gammaglobulin for Sickle Cell Pain Crises

NCT ID: NCT01757418

Last Updated: 2025-12-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

300 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-11-30

Study Completion Date

2024-12-18

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.

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

Conditions

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Sickle Cell Disease Pain

Keywords

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Pain Immune Globulin Sickle Cell Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

1:1 randomization
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

Immune Globulin Intravenous (IVIG)

Intervention Type DRUG

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.

Normal saline

An equivalent volume (weight-based) of normal saline

Group Type PLACEBO_COMPARATOR

Normal saline

Intervention Type OTHER

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

Interventions

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Immune Globulin Intravenous (IVIG)

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.

Intervention Type DRUG

Normal saline

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

Intervention Type OTHER

Other Intervention Names

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GAMUNEX (Talecris Biotherapeutics) Placebo

Eligibility Criteria

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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)
Minimum Eligible Age

6 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Food and Drug Administration (FDA)

FED

Sponsor Role collaborator

Case Western Reserve University

OTHER

Sponsor Role collaborator

Grifols Therapeutics LLC

INDUSTRY

Sponsor Role collaborator

Albert Einstein College of Medicine

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kerry Morrone, MD

Role: PRINCIPAL_INVESTIGATOR

Albert Einstein College of Medicine

Locations

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Montefiore Medical Center

The Bronx, New York, United States

Site Status

Countries

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United States

References

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Chang J, Shi PA, Chiang EY, Frenette PS. Intravenous immunoglobulins reverse acute vaso-occlusive crises in sickle cell mice through rapid inhibition of neutrophil adhesion. Blood. 2008 Jan 15;111(2):915-23. doi: 10.1182/blood-2007-04-084061. Epub 2007 Oct 11.

Reference Type BACKGROUND
PMID: 17932253 (View on PubMed)

Turhan A, Jenab P, Bruhns P, Ravetch JV, Coller BS, Frenette PS. Intravenous immune globulin prevents venular vaso-occlusion in sickle cell mice by inhibiting leukocyte adhesion and the interactions between sickle erythrocytes and adherent leukocytes. Blood. 2004 Mar 15;103(6):2397-400. doi: 10.1182/blood-2003-07-2209. Epub 2003 Nov 20.

Reference Type BACKGROUND
PMID: 14630831 (View on PubMed)

Shi PA, Manwani D, Olowokure O, Nandi V. Serial assessment of laser Doppler flow during acute pain crises in sickle cell disease. Blood Cells Mol Dis. 2014 Dec;53(4):277-82. doi: 10.1016/j.bcmd.2014.04.001. Epub 2014 May 21.

Reference Type BACKGROUND
PMID: 24857171 (View on PubMed)

Manwani D, Frenette PS. Vaso-occlusion in sickle cell disease: pathophysiology and novel targeted therapies. Blood. 2013 Dec 5;122(24):3892-8. doi: 10.1182/blood-2013-05-498311. Epub 2013 Sep 19.

Reference Type BACKGROUND
PMID: 24052549 (View on PubMed)

Manwani D, Chen G, Carullo V, Serban S, Olowokure O, Jang J, Huggins M, Cohen HW, Billett H, Atweh GF, Frenette PS, Shi PA. Single-dose intravenous gammaglobulin can stabilize neutrophil Mac-1 activation in sickle cell pain crisis. Am J Hematol. 2015 May;90(5):381-5. doi: 10.1002/ajh.23956. Epub 2015 Apr 1.

Reference Type BACKGROUND
PMID: 25616042 (View on PubMed)

Manwani D, Xu C, Lee SK, Amatuni G, Cohen HW, Carullo V, Morrone K, Davila J, Shi PA, Ireland K, Keenan J, Frenette PS. Randomized phase 2 trial of Intravenous Gamma Globulin (IVIG) for the treatment of acute vaso-occlusive crisis in patients with sickle cell disease: Lessons learned from the midpoint analysis. Complement Ther Med. 2020 Aug;52:102481. doi: 10.1016/j.ctim.2020.102481. Epub 2020 Jun 9.

Reference Type BACKGROUND
PMID: 32951731 (View on PubMed)

Jang JE, Hidalgo A, Frenette PS. Intravenous immunoglobulins modulate neutrophil activation and vascular injury through FcgammaRIII and SHP-1. Circ Res. 2012 Apr 13;110(8):1057-66. doi: 10.1161/CIRCRESAHA.112.266411. Epub 2012 Mar 13.

Reference Type BACKGROUND
PMID: 22415018 (View on PubMed)

Other Identifiers

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FD-R-005341-01

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

09-06-172

Identifier Type: -

Identifier Source: org_study_id

NCT00644865

Identifier Type: -

Identifier Source: nct_alias