Intravenous Gammaglobulin for Sickle Cell Pain Crises

March 27, 2026 updated by: Albert Einstein College of Medicine

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

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)

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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

Enrollment (Actual)

300

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • The Bronx, New York, United States, 10467
        • Montefiore Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years to 65 years (Child)

Accepts Healthy Volunteers

No

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: Immune Globulin Intravenous (IVIG)
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.
Other Names:
  • GAMUNEX (Talecris Biotherapeutics)
Placebo Comparator: Normal saline
An equivalent volume (weight-based) of normal saline
Other: Normal saline
A single dose of normal saline administered within 24 hours of hospital admission for uncomplicated pain crisis.
Other Names:
  • Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Length of vaso-occlusive crisis (VOC)
Time Frame: 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.
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
Time Frame: From study drug infusion to end of crisis, average 4 days and maximum 30 days
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.
From study drug infusion to end of crisis, average 4 days and maximum 30 days
Time to end of vaso-occlusive crisis
Time Frame: Number of days from start of study drug infusion to end of crisis, average 4 days and maximum 30 days
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.
Number of days from start of study drug infusion to end of crisis, average 4 days and maximum 30 days
Length of Hospitalization
Time Frame: From admission to discharge, average 4 days and maximum 30 days
Length (duration) of Hospitalization will be summarized by study arm in months/days using univariate statistics.
From admission to discharge, average 4 days and maximum 30 days
Change in Macrophage-1 Antigen (Mac-1) expression
Time Frame: From Pre-infusion to 24-hours post-infusion
Change in Mac-1 expression levels from prior to infusion to 24 hours following infusion will be assessed by the appropriate in vitro adhesion assay to measure adhesion to cellular surfaces. Mac-1 is a cell surface receptor found on lymphocytes and leukocytes and serves as a marker for binding and adhesion. Mac-1 expression levels increase upon activation by inflammatory stimuli leading to a higher concentration of Mac-1 molecules on the cell's surface. Percentage change in Mac-1 from pre-infusion will be summarized by study arm using univariate statistics.
From Pre-infusion to 24-hours post-infusion
Change in Lactate Dehydrogenase (LDH) levels
Time Frame: From Pre-infusion to 24-hours post-infusion
Change in LDH levels from prior to infusion to 24 hours following infusion will be assessed. Percentage change in LDH concentration (in U/L) from pre-infusion will be summarized by study arm using univariate statistics. While normal LDH ranges vary by age/gender and thresholds have not been established for this study, higher LDH levels may serve as inflammatory biomarkers of hemolysis in patients with sickle cell disease and also be indicators of acute or chronic tissue damage.
From Pre-infusion to 24-hours post-infusion
Change in Hemoglobin (Hb) levels
Time Frame: From Pre-infusion to 24-hours post-infusion
Change in Hb levels from prior to infusion to 24 hours following infusion will be assessed. Percentage change in Hb concentration (in g/dL) from pre-infusion will be summarized by study arm using univariate statistics. While normal Hb ranges vary by age/gender and thresholds have not been established for this study, in patients with sickle cell disease, decreased Hb levels may be indicative of anemia, increased risk of thromboembolic events, and organ and tissue damage.
From Pre-infusion to 24-hours post-infusion
Change in High-sensitivity C-reactive protein (hsCRP) levels
Time Frame: From admission to 24-hours post-infusion, average 4 days
Change in hsCRP levels from admission to 24 hours following infusion will be assessed. Percentage change in hsCRP concentration (in mg/L) from admission will be summarized by study arm using univariate statistics. hsCRP serves a biomarker for inflammation. While normal ranges for hsCRP vary by age/gender and thresholds have not been established for this study, higher hsCRP levels may serve as a laboratory correlate of hospitalizations for pain or vaso-occlusive events in patients with sickle cell disease.
From admission to 24-hours post-infusion, average 4 days
Rate of transfer to Intensive Care Unit (ICU)
Time Frame: From admission to discharge, average 4 days and maximum 30 days
The percentage of patients who are admitted to the hospital's ICU for an emergent condition will be summarized by study arm.
From admission to discharge, average 4 days and maximum 30 days
Diagnosis leading to transfer to the ICU
Time Frame: From admission to discharge, average 4 days and maximum 30 days
Diagnoses leading to transfer to the ICU will be summarized by study arm.
From admission to discharge, average 4 days and maximum 30 days
Number and type of Transfusions
Time Frame: From study drug infusion to discharge, average 4 days and maximum 30 days
The number and types of intervening packed red blood cell transfusions administered during the study will be summarized by study arm. Types of red blood cell transfusions will be categorized (e.g., acute, intermittent, chronic, simple, exchange) and will be administered as clinically indicated and ordered by the physician in accordance with NIH-NHLBI evidence-based management of sickle cell disease guidelines.
From study drug infusion to discharge, average 4 days and maximum 30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Albert Einstein College of Medicine

Collaborators

Food and Drug Administration (FDA)
Case Western Reserve University
Grifols Therapeutics LLC

Investigators

  • Principal Investigator: Kerry Morrone, MD, Albert Einstein College of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2008

Primary Completion (Actual)

December 18, 2024

Study Completion (Actual)

December 18, 2024

Study Registration Dates

First Submitted

November 8, 2012

First Submitted That Met QC Criteria

December 21, 2012

First Posted (Estimated)

December 31, 2012

Study Record Updates

Last Update Posted (Actual)

March 31, 2026

Last Update Submitted That Met QC Criteria

March 27, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 09-06-172
  • FD-R-005341-01 (Other Grant/Funding Number: FDA, OOPD)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Pain

Clinical Trials on Normal saline

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Armenia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe