Intravenous Immunoglobulin for Small Fiber Neuropathy

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether intravenous immunoglobulin (IVIG) can benefit individuals with small fiber neuropathy, a condition causing nerve pain and numbness. Researchers believe that those with certain autoantibodies might experience improved nerve function and reduced pain after treatment. The study compares IVIG treatment to a placebo (a saltwater solution) to determine its effectiveness. Suitable participants have noticeable nerve pain, confirmed nerve damage from a skin biopsy, and specific autoantibodies. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to important findings.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that intravenous immunoglobulin (IVIG) is generally safe. In one study, participants who received IVIG did not experience more serious issues, such as kidney failure or lung injury, compared to those who received a placebo. This study reported no unexpected side effects.

However, IVIG can have side effects. Common ones include headaches, nausea, and reactions at the injection site. Serious problems, like kidney issues, can occur but are more likely in individuals with certain existing health conditions. As this is a Phase 2 trial, earlier studies have already demonstrated some safety, but further testing aims to gather more detailed information on its safety and effectiveness. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for small fiber neuropathy?

Unlike the standard treatments for small fiber neuropathy, which often include pain management through medications like gabapentin or pregabalin, this new approach uses intravenous immunoglobulin (IVIg) to target the underlying autoimmune component of the disease. Researchers are excited because IVIg has the potential to modulate the immune system by neutralizing harmful antibodies, which might offer a more effective treatment by addressing the root cause rather than just alleviating symptoms. Additionally, IVIg's approach could provide a new avenue for patients who don't respond adequately to conventional therapies, bringing hope for better long-term outcomes.

What evidence suggests that intravenous immunoglobulin might be an effective treatment for small fiber neuropathy?

Research has shown that intravenous immunoglobulin (IVIG), which participants in this trial may receive, can help treat immune system-related problems. For example, studies have found it benefits people with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), a condition that damages nerves, by improving their ability to function and reducing flare-ups. Another study found that IVIG lowered disease activity in various autoimmune conditions, where the body mistakenly attacks itself. While these studies focused on other diseases, they suggest IVIG might also help with small fiber neuropathy by addressing similar immune-related issues. This treatment could potentially increase nerve fiber density and lessen pain. ^{6 7 8 9 10}

Who Is on the Research Team?

Christopher Gibbons, MD

Principal Investigator

Beth Israel Deaconess Medical Cednter

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

• Intravenous immunoglobulin

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 (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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40247653/

The Results of ADVANCE-CIDP IVIG Trial Conclusions: IVIG 10% effectively treated CIDP relapse and improved functional abilities. Keywords: chronic inflammatory demyelinating polyradiculoneuropathy; ...

2. annallergy.org annallergy.org/article/S1081-1206(24)01506-0/fulltext

Outcomes of intravenous immunoglobulin treatment ... Secondary clinical outcomes included hospital readmission within 30 days of discharge, death during hospitalization, and serious adverse effects ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1568997224002015

Intravenous immunoglobulin as a therapy for autoimmune ... The results demonstrated a notable efficacy of immunoglobulin in reducing disease activity and in tapering the dose of systemic corticosteroids ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40095398/

A Comparative Real-World Study Evaluating the Safety of ... Thrombotic events, AKI, and hemolytic events were rare among patients with CIDP receiving IVIG. There were no consistently different outcome risks.

5. neurology.org neurology.org/doi/10.1212/NXI.0000000000200011

Long-term Effectiveness of IVIg Maintenance Therapy in 36 ... This is a large study in 36 patients with SPS demonstrating that monthly maintenance IVIg therapy offers long-term benefits in 67% of patients for a median 3.3 ...

6. labeling.cslbehring.com labeling.cslbehring.com/SDS/AU/Privigen/EN/Privigen-Safety-Data-Sheet.pdf

Privigen® - CSL Behring IMPORTANT NOTICE: This Safety Data Sheet (SDS) is prepared by CSL Behring in accordance with Safe Work. Australia National Code of Practice for the ...

7. gammagard.com gammagard.com/hcp/pidd/safety

GAMMAGARD LIQUID 10% IVIG & SCIG Safety & ARs | HCP Renal dysfunction, acute renal failure, osmotic nephrosis, and death may occur in predisposed patients with immune globulin intravenous (IGIV) products.

8. fda.gov fda.gov/files/vaccines,%20blood%20&%20biologics/published/Package-Insert----Gamunex-C.pdf

Package Insert - Gamunex-C The most common adverse reactions observed in ≥ 5% patients were (6.1): PI: Intravenous: Headache, cough, injection site reaction, nausea, pharyngitis and ...

9. labeling.cslbehring.com labeling.cslbehring.com/SDS/CORE/Privigen/EN/Privigen-Safety-Data-Sheet.pdf

Privigen - CSL Behring Immune Globulin Intravenous (Human), 10% Liquid for intravenous ... Details of the supplier of the safety data sheet. Company Name. CSL Behring ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5644268/

Demonstration of safety of intravenous immunoglobulin in ... IGIV-treated subjects did not experience higher rates of renal failure, lung injury, or thrombotic events than the placebo group. There were no unexpected ...