IVIG in the Treatment of Autoimmune Small Fiber Neuropathy With TS-HDS, FGFR-3, or Plexin D1 Antibodies

Intravenous Immunoglobulin (IVIG) in the Treatment of Small Fiber Neuropathy Due to TS-HDS, FGFR-3, or Plexin D1 Antibodies: a Double Blinded Placebo-controlled Phase II Trial

IVIG in the Treatment of Autoimmune Small Fiber Neuropathy With TS-HDS, FGFR-3, or Plexin D1 Antibodies (NCT04153422) is a Phase 2 interventional studying Small Fiber Neuropathy and Autoimmune Small Fiber Neuropathy, sponsored by Endeavor Health. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

This study will enroll patients with small fiber neuropathy (SFN). The study will look at an intravenous immunoglobulin (IVIG) called Panzyga. Panzyga is approved by the FDA as a therapy for Primary humoral immunodeficiency (PI) in patients 2 years of age and older; Chronic immune thrombocytopenia (ITP) in adults and Chronic inflammatory demyelinating polyneuropathy (CIDP) in adults. It has not been approved by the FDA for use in SFN. There is mounting evidence that Intravenous Immunoglobulin (IVIG) can cause pain reduction and improve objective nerve fiber densities on skin biopsies in great numbers in SFN patients. The primary outcome is quantified improvement in intraepidermal nerve fiber density (IENFD) on repeat skin punch biopsy after 6 months of IVIG treatment.

What Stage of Research Is This?

Phase 2 trials evaluate whether a treatment actually works against Small Fiber Neuropathy and continue monitoring side effects. Phase 2 enrolls larger groups (typically 100–300 patients) and produces the first real efficacy signal. A successful Phase 2 readout is what unlocks the much larger Phase 3 confirmatory trials needed for FDA approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

With a target enrollment of 20 participants, this is a small study — typical of early-phase research, rare-disease trials, or pilot studies designed to generate preliminary signal before a larger study is launched.

Who May Be Eligible (Plain English)

Who May Qualify: 1. Patients ≥ age 18 2. Patient with clinical and biopsy evidence of pure small fiber neuropathy (with or without dysautonomia) as evidenced by reduced IENFD on skin biopsy using PGP 9.5 as the immunostain. Biopsy must have been performed within 12 months of study enrollment. If biopsies were not done at CRL, they will be repeated and done at 3 sites (upper and lower thigh, lower calf), to have consistent and equivalent biopsy data with the follow up biopsy done after 6 mos of treatment 3. Patients must have elevated and/or abnormal titers of autoantibodies to TS-HDS-IgM, FGFR3-IgG, or Plexin-D1 measured by the Washington University Neuromuscular Laboratory (St Louis) within 12 mos of enrollment 4. Patients must have a baseline pain score on a visual analogue scale (VAS) of Greater or equal to 4/10 5. Patients must have a baseline Utah Early Neuropathy Scale (UENS) score of Greater or equal to 4/10 6. Small Fiber Neuropathy Screening List (SFNSL) score of 11/84 or greater 7. Non-pregnant, non-lactating female. Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during treatment Who Should NOT Join This Trial: 1. Any other known cause for small fiber neuropathy other than the presence of the elevated titers of TS-HDS-IgM, FGFR3-IgG, or Plexin-D1 autoantibodies 2. Patients with generalized, severe musculoskeletal conditions other than SFN that prevent a sufficient assessment of the patient by the physician 3. Electromyography/nerve conduction study (EMG/NCS) evidence of large fiber polyneuropathy, to be confirmed by study PI 4. Underlying severe heart, kidney, liver disease, or HIV infection, (Note: If there is no previous HIV test result documented within the last 5 years, a test may be performed in order to confirm eligibility) ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: 1. Patients ≥ age 18 2. Patient with clinical and biopsy evidence of pure small fiber neuropathy (with or without dysautonomia) as evidenced by reduced IENFD on skin biopsy using PGP 9.5 as the immunostain. Biopsy must have been performed within 12 months of study enrollment. If biopsies were not done at CRL, they will be repeated and done at 3 sites (upper and lower thigh, lower calf), to have consistent and equivalent biopsy data with the follow up biopsy done after 6 mos of treatment 3. Patients must have elevated and/or abnormal titers of autoantibodies to TS-HDS-IgM, FGFR3-IgG, or Plexin-D1 measured by the Washington University Neuromuscular Laboratory (St Louis) within 12 mos of enrollment 4. Patients must have a baseline pain score on a visual analogue scale (VAS) of Greater or equal to 4/10 5. Patients must have a baseline Utah Early Neuropathy Scale (UENS) score of Greater or equal to 4/10 6. Small Fiber Neuropathy Screening List (SFNSL) score of 11/84 or greater 7. Non-pregnant, non-lactating female. Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during treatment Exclusion Criteria: 1. Any other known cause for small fiber neuropathy other than the presence of the elevated titers of TS-HDS-IgM, FGFR3-IgG, or Plexin-D1 autoantibodies 2. Patients with generalized, severe musculoskeletal conditions other than SFN that prevent a sufficient assessment of the patient by the physician 3. Electromyography/nerve conduction study (EMG/NCS) evidence of large fiber polyneuropathy, to be confirmed by study PI 4. Underlying severe heart, kidney, liver disease, or HIV infection, (Note: If there is no previous HIV test result documented within the last 5 years, a test may be performed in order to confirm eligibility) 5. Patients with a history of deep vein thrombosis within the last year prior to baseline visit or pulmonary embolism ever; patients with susceptibility to embolism or deep vein thrombosis 6. Known significant IgA deficiency with antibodies to IgA 7. History of hypersensitivity, anaphylaxis or severe systemic response to immuno-globulin, blood or plasma derived products, or any component of IVIG 10% 8. Known blood hyperviscosity, or other hypercoagulable states 9. Use of IgG products within six months prior to enrollment 10. Patients with a history of drug or alcohol abuse within the past five years prior to enrollment 11. Patients unable to understand or unwilling or unable to comply with the study protocol

Treatments Being Tested

DRUG

Panzyga IVIG

Immune Globulin Infusion 10% (Human)

DRUG

Placebo

0.9% NaCl prepared as the calculated dose equivalent volume to IVIG.

Locations (1)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Endeavor Health

Glenview, Illinois, United States

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT04153422), the sponsor (Endeavor Health), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT04153422 clinical trial studying?

This study will enroll patients with small fiber neuropathy (SFN). The study will look at an intravenous immunoglobulin (IVIG) called Panzyga. Panzyga is approved by the FDA as a therapy for Primary humoral immunodeficiency (PI) in patients 2 years of age and older; Chronic immune thrombocytopenia (ITP) in adults and Chronic inflammatory demyelinating polyneuropathy (CIDP) in adults. It has not been approved by the FDA for use in SFN. There is mounting evidence that Intravenous Immunoglobulin (IVIG) can cause pain reduction and improve objective nerve fiber densities on skin biopsies in great… The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT04153422?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT04153422?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT04153422. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT04153422. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.