IVIG for Small Fiber Neuropathy

Recruiting at 1 trial location

Overseen By Maria Stotland, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Loyola University

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

Compensation: Varies

Number of Visits: 6

Duration: 24 weeks

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial will test a treatment called Panzyga on patients with small fiber neuropathy (SFN). SFN patients often suffer from undiagnosed pain, and current treatments have many side effects. Panzyga may help by reducing inflammation and improving nerve function, potentially reducing pain and increasing nerve density in the skin. Panzyga has been shown to be effective in treating various autoimmune neurological disorders and has potential benefits for managing neuropathic pain.

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

The trial protocol does not specify whether you need to stop taking your current medications. However, you cannot have used IgG products within six months prior to enrollment.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you have used IgG products in the last six months, you cannot participate in the trial.

What data supports the idea that the drug for Small Fiber Neuropathy is an effective treatment?

The available research shows that intravenous immunoglobulin (IVIG) has been effective in treating various nerve-related conditions. For example, in patients with autoimmune small fiber polyneuropathy, IVIG has shown significant benefits. Additionally, in studies involving other conditions like chronic inflammatory demyelinating polyneuropathy (CIDP), IVIG improved grip strength and overall muscle function. While these studies focus on different conditions, they suggest that IVIG can be effective for nerve-related issues, which supports its potential use for Small Fiber Neuropathy. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Gammagard IVIG for treating small fiber neuropathy?

Research shows that intravenous immunoglobulin (IVIG) therapy, like Gammagard, has been effective in treating other nerve-related conditions such as Guillain-Barre syndrome and chronic inflammatory demyelinating polyneuropathy. This suggests it might also help with small fiber neuropathy, although specific studies for this condition are still needed. ^{1 2 3 4 5}

What safety data exists for IVIG treatment in small fiber neuropathy?

IVIG is generally considered a safe treatment for neuropathies, including small fiber neuropathy, but it can have complications. Common mild reactions include infusion-related issues, which can often be managed by adjusting the infusion rate or using symptomatic medications. Serious adverse effects are rare but can include thromboembolic events, renal failure, anaphylaxis, or aseptic meningitis. Patients with IgA deficiency, preexisting renal insufficiency, or those using sucrose-containing IVIG preparations are at higher risk for certain complications. Screening for risk factors can help reduce these risks. In patients with autonomic dysfunction, aseptic meningitis or severe headaches are more common when IVIG is dosed traditionally. ^{2 4 6 7 8}

Is IVIG generally safe for treating small fiber neuropathy?

IVIG is generally considered safe for treating various neuropathies, but mild infusion-related reactions like headaches can occur. Serious side effects are rare but can include blood clots, kidney problems, or allergic reactions, especially in people with certain risk factors. ^{2 4 6 7 8}

Is the drug Gammagard IVIG, Panzyga IVIG, or Placebo a promising treatment for Small Fiber Neuropathy?

Yes, the drug Gammagard IVIG and Panzyga IVIG are promising treatments for Small Fiber Neuropathy. Research shows that intravenous immunoglobulin (IVIG) therapy has been effective in treating autoimmune forms of neuropathy, including small fiber neuropathy, by improving nerve function and reducing pain. ^{1 2 3 9 10}

How is the drug Gammagard IVIG different from other treatments for small fiber neuropathy?

Gammagard IVIG is unique because it is an intravenous immunoglobulin therapy that targets the immune system, which may help in conditions like small fiber neuropathy that are thought to have an immune component. This approach is different from other treatments that might not address the immune system directly. ^{1 2 3 9 10}

Research Team

Lawrence Zeidman, MD, FAAN

Principal Investigator

Henry Ford Health

Eligibility Criteria

This trial is for adults over 18 with small fiber neuropathy (SFN) confirmed by skin biopsy and specific autoantibodies (TS-HDS-IgM, FGFR3-IgG, Plexin-D1). Participants must have moderate pain and no history of severe reactions to immunoglobulin or blood products, significant heart, kidney, liver disease, HIV infection or recent deep vein thrombosis.

Inclusion Criteria

My lab tests show abnormal levels of specific autoantibodies.

I am not pregnant or breastfeeding.

I am 18 years old or older.

Exclusion Criteria

I am willing and able to follow the study's requirements.

I have not used IgG products in the last 6 months.

My small fiber neuropathy is not caused by anything other than novel auto-antibodies.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 2g/kg IVIG every 4 weeks over 2 days for 24 weeks

24 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Gammagard IVIG
• Panzyga IVIG
• Placebo

Trial Overview The study tests Panzyga IVIG's effectiveness in SFN patients. It compares the change in nerve fiber density after six months between those receiving Panzyga and a placebo. The goal is to see if Panzyga can reduce pain and improve nerve function.

Participant Groups

Group I: Treatment (IVIG) Experimental Treatment 1 Intervention

Patients in the treatment arm will receive 2g/kg IVIG every 4 weeks (over 2 days, 1g/kg dose on Day 1 and 1g/kg dose on Day 2) for 24 weeks (6 doses total).

Group II: Placebo Placebo Group 1 Intervention

Patients in the placebo arm will receive 0.9% NaCl infusions on the same schedule as the active treatment group (Day 1 and Day 2 every 4 weeks for 24 weeks total, (6 doses).

Gammagard IVIG is already approved in United States, European Union for the following indications:

Approved in United States as Gammagard for:

• Primary humoral immunodeficiency (PI)
• Chronic immune thrombocytopenia (ITP)
• Chronic inflammatory demyelinating polyneuropathy (CIDP)
• Multifocal motor neuropathy
• Kawasaki disease

Approved in European Union as Gammagard for:

• Primary immunodeficiency syndromes
• Chronic immune thrombocytopenia (ITP)
• Chronic inflammatory demyelinating polyneuropathy (CIDP)
• Multifocal motor neuropathy

Who Is Running the Clinical Trial?

Loyola University

Lead Sponsor

Trials

161

Recruited

31,400+

Henry Ford Health System

Lead Sponsor

Trials

334

Recruited

2,197,000+

Octapharma USA, Inc.

Collaborator

Trials

1

Recruited

20+

Findings from Research

In an open trial involving 19 patients with multifocal motor neuropathy and polyneuropathy associated with monoclonal gammopathy, intravenous human immune globulin (IVIg) showed significant initial improvement in 3 out of 6 patients with multifocal motor neuropathy, indicating its potential efficacy in treating immune-mediated neuropathies.

IVIg also benefited patients with polyneuropathy associated with IgM monoclonal gammopathy, with 4 out of 7 previously treated with immunosuppression showing improvement, suggesting that IVIg can be an effective treatment option for various forms of immune-mediated neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human immunoglobulin treatment of multifocal motor neuropathy and polyneuropathy associated with monoclonal gammopathy. Leger, JM., Younes-Chennoufi, AB., Chassande, B., et al.[2019]

Intravenous immunoglobulin therapy is effective for treating autoimmune small fiber polyneuropathies, which can cause disabling forms of dysautonomia, and is FDA approved for several immune-mediated peripheral nerve disorders.

However, patients receiving this therapy may experience a higher incidence of side effects, such as aseptic meningitis and severe headaches, particularly when traditional dosing methods are used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How We Treat Autoimmune Small Fiber Polyneuropathy with Immunoglobulin Therapy. Schofield, JR., Chemali, KR.[2019]

In a double-blind randomized controlled trial involving 60 patients with idiopathic small fiber neuropathy (I-SFN), IV immunoglobulin (IVIG) treatment did not significantly reduce pain compared to placebo, with only 40% of IVIG patients experiencing a meaningful pain reduction versus 30% in the placebo group.

The study provides Class I evidence indicating that IVIG is not an effective treatment for pain in patients with painful I-SFN, as no significant differences were observed in other outcomes such as general well-being and overall functioning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous Immunoglobulin Therapy in Patients With Painful Idiopathic Small Fiber Neuropathy. Geerts, M., de Greef, BTA., Sopacua, M., et al.[2022]

Intravenous immunoglobulin (IVIG) IgPro10 (Privigen) demonstrated significant efficacy in treating chronic inflammatory demyelinating polyneuropathy (CIDP), with a pooled INCAT response rate of 71.5% among 235 subjects, and a median time to improvement of 4.3 weeks.

The treatment was found to be safe, with an adverse drug reaction (ADR) rate of 44.7%, translating to 0.144 ADRs per infusion, indicating that while side effects occurred, they were manageable in this population, primarily consisting of pre-treated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of IVIG in CIDP: Combined data of the PRIMA and PATH studies. Merkies, ISJ., van Schaik, IN., Léger, JM., et al.[2021]

In a randomized controlled trial involving 25 patients, IV immunoglobulin (IVIg) treatment did not significantly reduce disability compared to placebo, as indicated by Overall Neuropathy Limitation Scale (ONLS) scores after 3 months.

Secondary outcomes, including strength and quality of life measures, also showed no significant differences between IVIg and placebo, suggesting that IVIg may not be an effective treatment for patients with diabetes and demyelinating polyneuropathy features.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, controlled crossover study of IVIg for demyelinating polyneuropathy and diabetes. Breiner, A., Barnett Tapia, C., Lovblom, LE., et al.[2020]

The ProCID study involving 142 patients with chronic inflammatory demyelinating polyneuropathy (CIDP) found that infusions of 10% liquid intravenous immunoglobulin (IVIg) at doses up to 2.0 g/kg were safe and well tolerated, with a high tolerance rate of 94.4% for the maximum infusion rate.

While 60.5% of treatment-emergent adverse events (TEAEs) were related to treatment, most were mild, and serious TEAEs were rare, indicating a favorable safety profile for IVIg in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Tolerability of Intravenous Immunoglobulin in Chronic Inflammatory Demyelinating Polyneuropathy: Results of the ProCID Study. Cornblath, DR., van Doorn, PA., Hartung, HP., et al.[2023]

Intravenous Immunoglobulin (IVIg) is a highly effective treatment for conditions like Guillain-Barré Syndrome (GBS) and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), supported by strong evidence for its efficacy.

While IVIg is generally safe, it can cause mild immediate side effects like headache and fever, and rare but serious complications such as anaphylaxis and thromboembolic events, highlighting the need for careful administration and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications of Immunoglobulin Therapy and Implications for Treatment of Inflammatory Neuropathy: A Review. Abbas, A., Rajabally, YA.[2019]

Intravenous immune globulin (IVIg) is a safe and effective treatment for autoimmune neuropathies, particularly when compared to alternatives like corticosteroids and chemotherapy, with a standard induction dose of 2 g/kg.

While mild infusion-related reactions are common, serious adverse effects are rare; however, certain patient conditions, such as IgA deficiency or renal insufficiency, can increase the risk of complications, highlighting the importance of screening for risk factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous gammaglobulin (IVIg) for treatment of CIDP and related immune-mediated neuropathies. Brannagan, TH.[2019]

Switching from intravenous immunoglobulin (IVIG) to subcutaneous immunoglobulin (SCIG) in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) or multifocal motor neuropathy (MMN) resulted in a slight increase in hemoglobin levels, indicating improved blood health.

The study showed that SCIG led to a reduction in hemolytic activity, as evidenced by improved haptoglobin, reticulocyte counts, and bilirubin levels, suggesting that SCIG may be a safer alternative to IVIG with less risk of hemolysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement of hemoglobin levels after a switch from intravenous to subcutaneous administration of immunoglobulin in chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy. Markvardsen, LH., Christiansen, I., Jakobsen, J.[2017]

In a pilot study involving 20 patients with small fiber neuropathies (SFN) associated with specific autoantibodies, intravenous immune globulin (IVIG) treatment did not show a significant improvement in nerve density or pain scores compared to placebo after 6 months.

Despite the treatment, both the IVIG and placebo groups exhibited similar changes in intra-epidermal nerve fiber density and pain levels, indicating that IVIG may not be an effective therapy for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind placebo-controlled pilot study of immunoglobulin for small fiber neuropathy associated with TS-HDS and FGFR-3 autoantibodies. Gibbons, CH., Rajan, S., Senechal, K., et al.[2023]

References

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

Human immunoglobulin treatment of multifocal motor neuropathy and polyneuropathy associated with monoclonal gammopathy. [2019]

2. Switzerland pubmed.ncbi.nlm.nih.gov

How We Treat Autoimmune Small Fiber Polyneuropathy with Immunoglobulin Therapy. [2019]

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

Intravenous Immunoglobulin Therapy in Patients With Painful Idiopathic Small Fiber Neuropathy. [2022]

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

Efficacy and safety of IVIG in CIDP: Combined data of the PRIMA and PATH studies. [2021]

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

Randomized, controlled crossover study of IVIg for demyelinating polyneuropathy and diabetes. [2020]

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

Safety and Tolerability of Intravenous Immunoglobulin in Chronic Inflammatory Demyelinating Polyneuropathy: Results of the ProCID Study. [2023]

7. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Complications of Immunoglobulin Therapy and Implications for Treatment of Inflammatory Neuropathy: A Review. [2019]

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

Intravenous gammaglobulin (IVIg) for treatment of CIDP and related immune-mediated neuropathies. [2019]

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

Improvement of hemoglobin levels after a switch from intravenous to subcutaneous administration of immunoglobulin in chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy. [2017]

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

A double-blind placebo-controlled pilot study of immunoglobulin for small fiber neuropathy associated with TS-HDS and FGFR-3 autoantibodies. [2023]