IVIG for Small Fiber Neuropathy

Recruiting at 2 trial locations

Overseen By Anna Pham

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Loyola University

Must not be taking: IgG products

Disqualifiers: Severe heart, kidney, liver disease, others

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether an intravenous immunoglobulin (IVIG) treatment called Panzyga can help people with small fiber neuropathy (SFN). SFN affects small nerve fibers and can cause pain and other symptoms. Researchers aim to determine if Panzyga can reduce pain and improve nerve health. Participants will receive either Panzyga or a placebo (a substance with no active medicine) to compare effects. The trial seeks individuals diagnosed with SFN, who have certain autoantibodies in their blood, and experience moderate to severe pain. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that treatments like Panzyga, administered through an IV, are generally safe. Studies have found that these treatments are well-tolerated for conditions such as Primary humoral immunodeficiency (PI) and Chronic inflammatory demyelinating polyneuropathy (CIDP). Reports comparing different IV treatments found no major safety differences among them.

For people with CIDP, IV treatments have been used successfully without unexpected risks. This suggests they might also be safe for conditions like small fiber neuropathy (SFN), although the FDA has not approved them for SFN yet. Since Panzyga is FDA-approved for other conditions, this adds confidence about its safety.

In summary, while any treatment can have side effects, existing evidence suggests that Panzyga is generally safe based on its use in other approved conditions. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about these IVIG treatments for small fiber neuropathy because they offer a new approach to managing this condition. Unlike typical treatments that may focus on pain relief or addressing symptoms, IVIG (intravenous immunoglobulin) treatments like Gammagard and Panzyga involve administering antibodies directly into the bloodstream, potentially targeting the underlying immune dysfunction thought to contribute to the nerve damage. This method could provide more comprehensive relief by addressing the root cause rather than just symptoms, offering hope for patients who may not respond to standard therapies like antidepressants, anticonvulsants, or topical treatments.

What evidence suggests that Panzyga IVIG might be an effective treatment for small fiber neuropathy?

Research has shown that intravenous immunoglobulin (IVIG) can benefit people with small fiber neuropathy (SFN). In this trial, participants in the treatment arm will receive IVIG, such as Panzyga. Studies have found that Panzyga can reduce pain and increase the number of nerve fibers in the skin of those with SFN. This suggests that IVIG might improve nerve function, offering hope for people with SFN. Although Panzyga is not yet approved specifically for SFN, it has successfully treated other nerve-related issues. This evidence indicates that IVIG could be a promising treatment for SFN. ^{3 5 6 7 8}

Who Is on the Research Team?

Lawrence Zeidman, MD, FAAN

Principal Investigator

Endeavor Health

Are You a Good Fit for This Trial?

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.

Your Small Fiber Neuropathy Screening List score is 11 or higher.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Endeavor Health

Lead Sponsor

Trials

135

Recruited

742,000+

Octapharma USA, Inc.

Collaborator

Trials

1

Recruited

20+

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12006664/

The Results of ADVANCE‐CIDP IVIG Trial ADVANCE‐CIDP IVIG evaluated the efficacy and safety of immune globulin infusion (human) 10% solution (IVIG 10%; GAMMAGARD LIQUID, also known as Kiovig)

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5791555/

IVIg for apparently autoimmune small-fiber polyneuropathy These results provide Class IV, real-world, proof-of-concept evidence suggesting that IVIg is safe and effective for rigorously selected SFPN patients with ...

3. withpower.com withpower.com/trial/phase-3-polyneuropathies-2022-073f4

IVIG for Small Fiber Neuropathy Research shows that intravenous immunoglobulin (IVIG) therapy, like Gammagard, has been effective in treating other nerve-related conditions such as Guillain- ...

4. gammagard.com gammagard.com/hcp/mmn/efficacy

GAMMAGARD LIQUID 10% MMN Clinical Trial Results | HCP Patients were randomized 1:1 to either double-blind treatment of GAMMAGARD LIQUID followed by placebo for 12 weeks each or the reverse. Open-label IVIG was ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04153422

IVIG in the Treatment of Autoimmune Small Fiber ... There is mounting evidence that Intravenous Immunoglobulin (IVIG) can cause pain reduction and improve objective nerve fiber densities on skin biopsies in great ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11912303/

A Comparative Real‐World Study Evaluating the Safety of ... Comparison of patients treated with GGL and other US‐approved IVIGs for CIDP showed no consistently different risks for the outcomes assessed. 1 ...

7. fda.gov fda.gov/media/175888/download

GAMMAGARD LIQUID Chronic Inflammatory Demyelinating Polyneuropathy (CIDP).” GAMMAGARD LIQUID is an immune globulin infusion (human) (IGI). It is a purified ...

8. uhcprovider.com uhcprovider.com/content/dam/provider/docs/public/policies/comm-medical-drug/immune-globulin-ivig-scig.pdf

Immune Globulin (IVIG and SCIG) According to ISBI practice guidelines, intravenous immune globulin (IVIG) is often given to patients who are hospitalized for Stevens-Johnson ...