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Intravenous Gammaglobulin for Sickle Cell Pain Crises

Primary Purpose

Sickle Cell Disease, Pain

Status

Recruiting

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Immune Globulin Intravenous

Normal saline

About this trial

This is an interventional treatment trial for Sickle Cell Disease focused on measuring Sickle Cell Disease, Pain, Immune Globulin

Eligibility Criteria

12 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Documented diagnosis of sickle cell disease (SS or S-β thalassemia genotype)
Age 12-65 years for Phase 1, 6-13.99 years for Phase 2
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

Sites / Locations

Montefiore Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Immune Globulin Intravenous

Normal saline

Arm Description

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.

An equivalent volume (weight-based)of normal saline

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

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

In vitro adhesion assays

Activated Mac-1, Aged neutrophils

Full Information

NCT ID

NCT01757418

First Posted

November 8, 2012

Last Updated

September 29, 2023

Sponsor

Deepa Manwani

1. Study Identification

Unique Protocol Identification Number

NCT01757418

Brief Title

Intravenous Gammaglobulin for Sickle Cell Pain Crises

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Recruiting

Study Start Date

November 2008 (undefined)

Primary Completion Date

December 2025 (Anticipated)

Study Completion Date

December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Deepa Manwani

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Sickle Cell Disease, Pain

Keywords

Sickle Cell Disease, Pain, Immune Globulin

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

300 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Immune Globulin Intravenous

Arm Type

Experimental

Arm Description

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.

Arm Title

Normal saline

Arm Type

Placebo Comparator

Arm Description

An equivalent volume (weight-based)of normal saline

Intervention Type

Drug

Intervention Name(s)

Immune Globulin Intravenous

Other Intervention Name(s)

GAMUNEX (Talecris Biotherapeutics)

Intervention Description

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

Other

Intervention Name(s)

Normal saline

Other Intervention Name(s)

Placebo

Intervention Description

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

Primary Outcome Measure Information:

Title

Length of vaso-occlusive crisis

Description

Time Frame

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

Secondary Outcome Measure Information:

Title

Total opioid use in equivalent of mg of IV morphine

Description

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

Time Frame

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

Title

Time to end of vaso-occlusive crisis

Description

Time Frame

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

Title

In vitro adhesion assays

Description

Activated Mac-1, Aged neutrophils

Time Frame

Pre and 24 hours post study drug

10. Eligibility

Sex

All

Minimum Age & Unit of Time

12 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Deepa G Manwani, M.D

Phone

718-741-2342

dmanwani@montefiore.org

First Name & Middle Initial & Last Name or Official Title & Degree

Karen Ireland

Phone

718-741-2401

kireland@montefiore.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Deepa G Manwani, M.D

Organizational Affiliation

Albert Einstein College of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Montefiore Medical Center

City

Bronx

State/Province

New York

ZIP/Postal Code

10467

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Deepa G Manwani, MD

Phone

718-741-2342

dmanwani@montefiore.org

First Name & Middle Initial & Last Name & Degree

Deepa G Manwani, MD

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

17932253

Citation

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.

Results Reference

background

PubMed Identifier

14630831

Citation

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.

Results Reference

background

PubMed Identifier

24857171

Citation

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.

Results Reference

result

PubMed Identifier

24052549

Citation

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.

Results Reference

result

PubMed Identifier

25616042

Citation

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.

Results Reference

result

PubMed Identifier

32951731

Citation

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.

Results Reference

result

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Intravenous Gammaglobulin for Sickle Cell Pain Crises

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