IV Gammaglobulin for Sickle Cell Pain Crises

No longer recruiting at 1 trial location

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if an intravenous treatment called immune globulin (also known as IV Gammaglobulin) can safely and effectively reduce pain during sickle cell disease crises. Participants will receive either the immune globulin treatment or a placebo (a harmless substance used for comparison). The trial seeks individuals with sickle cell disease who are experiencing a pain crisis requiring hospital care and pain medication. As a Phase 1, Phase 2 trial, it focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

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.

Is there any evidence suggesting that intravenous immune globulin is likely to be safe for humans?

Research has shown that intravenous immune globulin (IVIG) is already used for other medical conditions and is generally well-tolerated, meaning many people can take it without major issues. Studies have found that IVIG can help reduce certain harmful effects in the blood, especially in sickle cell disease, which is promising for those who experience pain crises.

Some trials have used doses as high as 800 mg/kg, while others are testing 400 mg/kg. Although these trials are ongoing, the use of IVIG in other conditions suggests that its safety is well understood. In simpler terms, doctors have a good understanding of how it works in the body and what side effects might occur. This makes it a safer option to explore for new uses, like helping with sickle cell pain crises. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for sickle cell pain crises?

Unlike the standard treatments for sickle cell pain crises, which often include pain management with opioids and blood transfusions, Intravenous Immune Globulin (IVIG) offers a unique approach. IVIG is derived from plasma and works by modulating the immune system, which is different from the typical pain relief or blood oxygenation strategies. Researchers are excited about IVIG because it targets the inflammatory processes that contribute to pain crises, potentially reducing their frequency and severity. This new mechanism of action could offer relief more quickly and with fewer side effects than traditional methods.

What evidence suggests that intravenous immune globulin might be an effective treatment for sickle cell pain crises?

Research suggests that Intravenous Immune Globulin (IVIG), which participants in this trial may receive, might help treat pain crises in people with sickle cell disease. Studies have found that IVIG can reduce the clumping of white and red blood cells in sickle cell models, potentially helping to clear blockages that cause pain during a crisis. In early trials with sickle cell patients, IVIG showed promise in reducing pain when given at a specific dose. While more information is needed, these findings suggest IVIG could be a helpful treatment for sickle cell pain crises. ^{1 2 3 4 6}

Who Is on the Research Team?

Kerry Morrone, MD

Principal Investigator

Albert Einstein College of Medicine

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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 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]

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 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]

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4409477/

Single-dose intravenous gammaglobulin can stabilize ... Intravenous immunoglobulin (IVIG) decreases neutrophil adhesion to endothelium and red blood cell-neutrophil interactions in sickle cell mice undergoing ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0965229919320606

Randomized phase 2 trial of Intravenous Gamma Globulin ... We are evaluating a single 400 mg/kg dose of IVIG (Gamunex) in an ongoing phase II clinical study in SCD patients that are hospitalized for VOC.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01757418

Intravenous Gammaglobulin for Sickle Cell Pain Crises 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 ...

4. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/488775

Intravenous Gammaglobulin for Sickle Cell Pain Crises The purpose of this study is to determine whether intravenous immune globulin is safe and effective in the acute treatment of pain crises in ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2200843/

Intravenous immunoglobulins reverse acute vaso ... Because this model reflects clinical vaso-occlusive painful crises, these data suggest that IVIG may be beneficial in the context of acute sickle cell crises.

6. researchgate.net researchgate.net/publication/342062372_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

Randomized Phase 2 trial of Intravenous Gamma Globulin ... Intravenous immunoglobulin (IVIG) decreases neutrophil adhesion to endothelium and red blood cell-neutrophil interactions in sickle cell mice ...