IVIg for Small Fiber Neuropathy With Autoantibodies TS-HDS and FGFR3

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Beth Israel Deaconess Medical Center

Must not be taking: IgG products

Disqualifiers: Diabetes, HIV, Hepatitis, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 18 weeks

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a treatment with healthy antibodies on patients with nerve damage and harmful antibodies. The goal is to see if this treatment can improve nerve health and reduce pain. This treatment has been used for nearly three decades for various neurological diseases.

Do I have to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. However, it does mention that you cannot have used IgG products within six months or other blood or plasma-derived products within three months prior to enrollment.

What data supports the effectiveness of the drug Intravenous immunoglobulin (IVIG)?

IVIG is used as a replacement therapy for patients with immunoglobulin deficiency and has shown potential in treating serious infectious diseases with limited alternative treatments. It is also used to prevent or treat primary immune deficiency, several infectious diseases, and autoimmune diseases, with some evidence suggesting it may help against emerging influenza viruses. ^{1 2 3 4 5}

Is intravenous immunoglobulin (IVIG) generally safe for humans?

IVIG is generally considered safe, but mild side effects like headache and nausea can occur, especially if the infusion is too fast. Severe reactions are rare, but people with certain conditions, like IgA deficiency, may have a higher risk of serious allergic reactions. Safety measures during manufacturing have reduced the risk of viral transmission. ^{6 7 8 9 10}

How is the drug IVIG different from other treatments for this condition?

IVIG is unique because it is a purified pool of human antibodies from thousands of donors, which can provide a broad range of immune support and is used to treat various immune-related conditions. Unlike other treatments, it can mediate antibody-dependent cellular cytotoxicity (ADCC) against different strains of influenza, making it potentially effective against emerging viruses. ^{2 3 5 7 11}

Research Team

Christopher Gibbons, MD

Principal Investigator

Beth Israel Deaconess Medical Cednter

Eligibility Criteria

Inclusion Criteria

Patient with clinically evident and biopsy proven pure small fiber neuropathy as evidenced by reduced intra-epidermal nerve fiber density seen on skin biopsy using PGP 9.5 as the immunostain.

Patients must have a baseline pain score on a VAS scale of Greater or equal to 4/10

Patients must have elevated titers of autoantibodies to TS-HDS or FFR3 as measured in Dr Alan Pestronk's lab at Washington University in St Louis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive IVIG or placebo treatment. IVIG is administered at an initial dose of 2 grams/kg over 2 days followed by 1 gram/kg over 1 day every 3 weeks for a total of 6 treatments.

18 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments of nerve fiber density and pain scores.

4-9 weeks

2 visits (in-person)

Treatment Details

Interventions

• Intravenous immunoglobulin

Participant Groups

Group I: Intravenous Immunoglobulin Experimental Treatment 1 Intervention

The study will include a total 20 individuals. Subjects will be randomized equally to treatment or placebo. Treatment will consist of IVIG administered at an initial dose of 2 grams/kg over 2 days followed by 1 gram/kg over 1 day every 3 weeks for a total of 6 treatments

Group II: 0.9% Sodium Chloride Placebo Group 1 Intervention

The study will include a total 20 individuals. Subjects will be randomized equally to treatment or placebo. The placebo will consist of 0.9% Sodium Chloride per day over 2 days. Followed by 0.9% Sodium Chloride over 1 day every 3 weeks for a total of 6 treatments. Participants who are randomized to placebo will receive the same volume as they would if they were randomized to IVIG (i.e.: as if receiving IVIG at 2gm/kg) through a peripheral IV line.

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

Approved in European Union as IVIG for:

• Primary immunodeficiency
• Chronic immune thrombocytopenic purpura
• Chronic inflammatory demyelinating polyneuropathy
• Multifocal motor neuropathy
• Systemic sclerosis

Approved in United States as IVIG for:

• Primary immunodeficiency
• Chronic immune thrombocytopenic purpura
• Chronic inflammatory demyelinating polyneuropathy
• Multifocal motor neuropathy
• Systemic sclerosis

Approved in Canada as IVIG for:

• Primary immunodeficiency
• Chronic immune thrombocytopenic purpura
• Chronic inflammatory demyelinating polyneuropathy
• Multifocal motor neuropathy
• Systemic sclerosis

Approved in Japan as IVIG for:

• Primary immunodeficiency
• Chronic immune thrombocytopenic purpura
• Chronic inflammatory demyelinating polyneuropathy
• Multifocal motor neuropathy
• Systemic sclerosis

Approved in Switzerland as IVIG for:

• Primary immunodeficiency
• Chronic immune thrombocytopenic purpura
• Chronic inflammatory demyelinating polyneuropathy
• Multifocal motor neuropathy
• Systemic sclerosis

Who Is Running the Clinical Trial?

Beth Israel Deaconess Medical Center

Lead Sponsor

Trials

872

Recruited

12,930,000+

Phoenix Neurological Associates, LTD

Collaborator

Trials

8

Recruited

220+

Findings from Research

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]

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 immunoglobulins (IVIgs) are generally considered safe for treating neuroimmunologic and autoimmune diseases, with severe complications being rare and often linked to preexisting risk factors.

While mild and self-limited side effects can occur, careful screening of patients and monitoring of laboratory parameters can help minimize the risks associated with IVIg therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side effects of high-dose intravenous immunoglobulins. Stangel, M., Hartung, HP., Marx, P., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

I.V. immunoglobulin therapy for infectious diseases. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Safety of intravenous immunoglobulin treatment. [2010]

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

Cross-reactive influenza-specific antibody-dependent cellular cytotoxicity in intravenous immunoglobulin as a potential therapeutic against emerging influenza viruses. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Antibody therapy (IVIG): evaluation of the use of genomics and proteomics for the study of immunomodulation therapeutics. [2015]

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

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

6. England pubmed.ncbi.nlm.nih.gov

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

7. Argentina pubmed.ncbi.nlm.nih.gov

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

8. Switzerland pubmed.ncbi.nlm.nih.gov

Anaphylaxis to IVIG. [2017]

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

Side effects of high-dose intravenous immunoglobulins. [2019]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Adverse effects of intravenous immunoglobulin. [2022]

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

Clinical indications for intravenous immunoglobulin utilization in a tertiary medical center: a 9-year retrospective study. [2019]