Intravenous Gammaglobulin for Sickle Cell Pain Crises

NCT01757418 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 09-06-172FD-R-005341-01
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

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)

Conditions

Sickle Cell Disease; Pain

Keywords

Sickle Cell Disease; Pain; Immune Globulin

Outcome Measures

Primary Outcomes (1)

• 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.

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

Secondary Outcomes (10)

• 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

Study Arms (2)

Intravenous Immune Globulin (IVIG)

EXPERIMENTAL

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 (IVIG)

Normal saline

PLACEBO COMPARATOR

An equivalent volume (weight-based) of normal saline

Other: Normal saline

Interventions

Normal saline OTHER

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

Also known as: Placebo

Normal saline

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.

Also known as: GAMUNEX (Talecris Biotherapeutics)

Intravenous Immune Globulin (IVIG)

Eligibility Criteria

• Age: 6 Years - 13 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Food and Drug Administration (FDA): collaborator
• Case Western Reserve University: collaborator
• Grifols Therapeutics LLC: collaborator
• Albert Einstein College of Medicine: lead

Study Sites (1)

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Related Publications (7)

• 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.

  PMID: 17932253 BACKGROUND

• 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.

  PMID: 14630831 BACKGROUND

• 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.

  PMID: 24857171 BACKGROUND

• 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.

  PMID: 24052549 BACKGROUND

• 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.

  PMID: 25616042 BACKGROUND

• 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.

  PMID: 32951731 BACKGROUND

• 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.

  PMID: 22415018 BACKGROUND

MeSH Terms

Conditions

Anemia, Sickle Cell; Pain

Interventions

gamma-Globulins; Immunoglobulins, Intravenous; Saline Solution

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Kerry Morrone, MD

  Albert Einstein College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 1:1 randomization

Study Record Dates

• First Submitted: November 8, 2012
• First Posted: December 31, 2012
• Study Start: November 1, 2008
• Primary Completion: December 18, 2024
• Study Completion: December 18, 2024
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)