IV Gammaglobulin for Sickle Cell Pain Crises

Overseen By Karen Ireland

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Deepa Manwani

Must be taking: Voxelotor

Must not be taking: Estrogen, Illicit drugs

Disqualifiers: Renal dysfunction, Stroke, Pregnancy, others

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Average 4 days, maximum 30 days

300 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are prescribed Voxelotor, you must either continue using it consistently or not have used it in the past week.

What data supports the effectiveness of the drug IV Gammaglobulin for Sickle Cell Pain Crises?

Intravenous gammaglobulin (IVIG) has been shown to be effective in improving immune function in patients with primary immunodeficiency diseases and preventing the progression of HIV-related conditions. It contains antibodies that help fight infections, which might suggest potential benefits in managing sickle cell pain crises, although direct evidence for this specific use is not provided. ^{1 2 3 4 5}

Is IV Gammaglobulin generally safe for humans?

IV Gammaglobulin, also known as IVIG, is generally considered safe for humans, but it can cause mild side effects like headaches, fever, and nausea. Rarely, it may lead to more serious issues like kidney problems or blood clots, especially in people with certain risk factors. Ensuring patients are well-hydrated and using a slow infusion rate can help minimize these risks. ^{2 6 7 8 9}

How does the drug IV Gammaglobulin differ from other treatments for sickle cell pain crises?

IV Gammaglobulin (IVIG) is unique because it is administered intravenously (through a vein) and is primarily used to boost the immune system in various conditions, including immunodeficiencies and autoimmune diseases. Unlike typical pain management for sickle cell crises, which often involves painkillers, IVIG may help by modulating immune responses, potentially offering a novel approach to managing the condition. ^{1 3 5 10 11}

What is the purpose of this trial?

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)

Research Team

Deepa G Manwani, M.D

Principal Investigator

Albert Einstein College of Medicine

Eligibility Criteria

This trial is for individuals aged 12-65 with sickle cell disease experiencing a pain crisis needing hospital care. It's open to those not on chronic transfusion or at high stroke risk, without recent live vaccines, illicit drug abuse history, certain blood levels (Hb >10 g/dL or <5 g/dL), pregnancy, thrombosis risks like estrogen use, suspected infections, kidney issues, other drug trials participation, IgA deficiency or gamma globulin allergies.

Inclusion Criteria

I have been diagnosed with sickle cell disease.

I was hospitalized for severe pain that needed strong painkillers given through an IV.

I am between 12 and 65 years old for Phase 1, or between 6 and 13.99 years old for Phase 2.

Exclusion Criteria

I have not received a live vaccine in the last 6 weeks.

I have had blood clots before or am currently using estrogen.

I currently have a fever over 101.3°F possibly due to an infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of IVIG or normal saline placebo during an uncomplicated pain crisis

Average 4 days, maximum 30 days

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in Mac-1, LDH, Hb, and hsCRP levels

24 hours post-infusion

Extended Monitoring

Participants are monitored for length of hospitalization and rate of transfer to ICU

Average 4 days, maximum 30 days

Treatment Details

Interventions

• Immune Globulin Intravenous

Trial Overview The study tests if intravenous immune globulin can safely and effectively treat acute pain crises in sickle cell disease compared to normal saline. Participants are hospitalized and receive either the immune therapy or a saline solution as part of the treatment process.

Participant Groups

Group I: Intravenous Immune Globulin (IVIG) Experimental Treatment 1 Intervention

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 II: Normal saline Placebo Group 1 Intervention

An equivalent volume (weight-based) of normal saline

Immune Globulin Intravenous is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Immune Globulin Intravenous for:

• Primary immunodeficiency
• Immune thrombocytopenic purpura
• Chronic inflammatory demyelinating polyneuropathy
• Kawasaki disease
• Guillain–Barré syndrome

Approved in United States as IVIG for:

• Primary immunodeficiency
• Immune thrombocytopenic purpura
• Chronic inflammatory demyelinating polyneuropathy
• Multifocal motor neuropathy

Approved in Canada as Human Normal Immunoglobulin for:

• Primary immunodeficiency
• Immune thrombocytopenic purpura
• Chronic inflammatory demyelinating polyneuropathy

Approved in Japan as Gammaglobulin for:

• Primary immunodeficiency
• Immune thrombocytopenic purpura

Who Is Running the Clinical Trial?

Deepa Manwani

Lead Sponsor

Trials

1

Recruited

300+

Albert Einstein College of Medicine

Lead Sponsor

Trials

302

Recruited

11,690,000+

Food and Drug Administration (FDA)

Collaborator

Trials

184

Recruited

1,553,000+

Case Western Reserve University

Collaborator

Trials

314

Recruited

236,000+

Grifols Therapeutics LLC

Industry Sponsor

Trials

59

Recruited

6,000+

Findings from Research

Intravenous administration of high-dose intact immunoglobulin (IVGG) in an HIV-infected hemophilia A patient led to a gradual increase in total lymphocyte and CD4 positive lymphocyte counts, suggesting a potential benefit for immune function.

The consistent results across multiple administrations indicate that IVGG may help prevent the decline of cellular immunity and the progression from asymptomatic HIV infection to AIDS-related complex or AIDS in hemophilia patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High dose intact-immunoglobulin treatment for an HIV-infected asymptomatic carrier with hemophilia. Akutsu, Y., Mori, K., Suzuki, S., et al.[2019]

Intravenous immunoglobulin (IVIG) is generally considered a safe treatment for various neurological disorders, but this report highlights a rare complication of arthritis linked to elevated immune complexes and serum complement abnormalities.

The findings suggest that while IVIG is effective, healthcare providers should be aware of potential rare side effects, such as arthritis, especially in patients with pre-existing immune system issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Arthritis associated with circulating immune complexes following administration of intravenous immunoglobulin therapy in a patient with chronic inflammatory demyelinating polyneuropathy. Lisak, RP.[2019]

In a study involving 35 patients with primary immunodeficiency diseases, treatment with polyethylenglicol treated intravenous gammaglobulin resulted in higher serum IgG levels compared to those previously treated with intramuscular gammaglobulin, indicating improved efficacy.

The intravenous gammaglobulin was generally well tolerated, with only two serious and two mild adverse reactions reported, highlighting its safety profile, although one patient developed IgE mediated antibodies against IgA after two years of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of primary immunodeficiencies with intravenous gamma globulin]. García Rodríguez, C., López Trascasa, M., Ferreira Cerdán, A., et al.[2006]

Intravenous immunoglobulin (IVIG) is a concentrated form of IgG that contains various antibacterial and antiviral antibodies, making it useful for treating certain immune-related conditions.

While IVIG is well-established for conditions like severe combined immunodeficiency, its effectiveness for other conditions such as immune thrombocytopenic purpura and chronic lymphocytic leukemia is still being researched.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous immunoglobulin in oncology nursing practice. Timmerman, PR.[2013]

In a study of 35 adults with humoral primary immunodeficiency diseases receiving intravenous immunoglobulin (IVIG), 51.4% showed signs of kidney damage, highlighting a significant risk associated with long-term IVIG treatment.

Patients treated with IVIG for more than 5 years had a higher incidence of chronic kidney disease (55.6%), indicating the need for regular kidney function monitoring and consideration of using sugar-free immunoglobulin to mitigate risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chronic kidney disease in adults with primary immunodeficiency diseases in treatment with intravenous immunoglobulin]. O'Farrill-Romanillos, PM., Luna-Mújica, RF., Contreras-García, CE., et al.[2021]

Intravenous immunoglobulins are essential for treating primary humoral immunodeficiencies and are also effective for various autoimmune, neurological, and hematological conditions, highlighting their versatility in medical treatment.

While generally well tolerated, intravenous immunoglobulins can cause a range of adverse reactions, so this review provides guidance for healthcare providers on minimizing and managing these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous immunoglobulin therapy: a snapshot for the internist. Vitiello, G., Emmi, G., Silvestri, E., et al.[2022]

Intravenous immunoglobulin (IVIg) is generally safe and effective for treating immunodeficiencies and autoimmune diseases, with mild and transient adverse effects occurring in 24-36% of patients, primarily headaches.

To minimize risks such as acute renal failure and thromboembolic events, IVIg should be administered at a slow infusion rate and in well-hydrated patients, especially avoiding those with known risk factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of intravenous immunoglobulin (IVIG) therapy. Katz, U., Achiron, A., Sherer, Y., et al.[2022]

In a study of 305 intravenous immunoglobulin G (IVIG) infusions given to 111 pediatric patients, only 3.9% of infusions resulted in adverse reactions, indicating a low incidence of side effects in this population.

The most severe adverse reactions included two cases of aseptic meningitis and one case of seizures, all of which resolved completely, suggesting that while IVIG is generally safe, monitoring for rare severe reactions is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous immunoglobulin G use and pharmacovigilance in a tertiary care children's hospital. Yori, S., Belleri, F., Testard, J., et al.[2021]

In an observational study involving patients treated with Human Normal Immunoglobulin 10% Liquid (IVIG 10%), 81.8% of subjects showed good or very good efficacy ratings by investigators over a follow-up period of 6 weeks to 12 months.

The treatment was well-tolerated, with 87.5% of subjects reporting good or very good tolerability, and only one serious adverse reaction (urticaria) noted, indicating a favorable safety profile similar to previous clinical studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human immunoglobulin (KIOVIG®/GAMMAGARD LIQUID®) for immunodeficiency and autoimmune diseases: an observational cohort study. Blažek, B., Misbah, SA., Soler-Palacin, P., et al.[2022]

Three patients experienced severe hemolysis after receiving intravenous immunoglobulin (IVIG) due to passively transferred anti-A antibodies, highlighting a potential risk associated with IVIG treatment.

Clinicians may overlook IVIG as a cause of hemolysis, especially since routine tests may not detect these passively transferred antibodies, which can lead to significant drops in hemoglobin levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haemolysis after treatment with intravenous immunoglobulin due to anti-A. Morgan, S., Sorensen, P., Vercellotti, G., et al.[2011]

Intravenous immunoglobulin (IVIG) preparations, developed to be well tolerated and safe for administration, have transformed the treatment of immunodeficiency syndromes and are effective in preventing infections in patients with compromised immune systems.

IVIG is also beneficial in treating certain autoimmune diseases, potentially due to its ability to inhibit harmful immune responses and protect cells from damage, showcasing its versatility beyond just infection prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Historic aspects of intravenous immunoglobulin therapy. Good, RA., Lorenz, E.[2019]

References

1. Japan pubmed.ncbi.nlm.nih.gov

High dose intact-immunoglobulin treatment for an HIV-infected asymptomatic carrier with hemophilia. [2019]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Arthritis associated with circulating immune complexes following administration of intravenous immunoglobulin therapy in a patient with chronic inflammatory demyelinating polyneuropathy. [2019]

3. Spain pubmed.ncbi.nlm.nih.gov

[Treatment of primary immunodeficiencies with intravenous gamma globulin]. [2006]

4. United States pubmed.ncbi.nlm.nih.gov

Intravenous immunoglobulin in oncology nursing practice. [2013]

5. Mexico pubmed.ncbi.nlm.nih.gov

[Chronic kidney disease in adults with primary immunodeficiency diseases in treatment with intravenous immunoglobulin]. [2021]

6. Italy pubmed.ncbi.nlm.nih.gov

Intravenous immunoglobulin therapy: a snapshot for the internist. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Safety of intravenous immunoglobulin (IVIG) therapy. [2022]

8. Argentina pubmed.ncbi.nlm.nih.gov

Intravenous immunoglobulin G use and pharmacovigilance in a tertiary care children's hospital. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Human immunoglobulin (KIOVIG®/GAMMAGARD LIQUID®) for immunodeficiency and autoimmune diseases: an observational cohort study. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Haemolysis after treatment with intravenous immunoglobulin due to anti-A. [2011]

11. United States pubmed.ncbi.nlm.nih.gov

Historic aspects of intravenous immunoglobulin therapy. [2019]