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

January 11, 2024 updated by: Lawrence Zeidman, MD, FAAN, Henry Ford Health System

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Small fiber neuropathy (SFN) is an increasingly prevalent diagnosis in neurology and neuromuscular centers. Modern diagnostic techniques, including skin biopsies and autonomic nervous testing are helping to find SFN in many patients with undiagnosed pain syndromes including fibromyalgia. The prevalence is rising for SFN, and an immune etiology may underlie 19%-34% of cases. While there is no standard of care treatment, current treatment strategies for SFN include long-term steroid therapy which come with a host of side effects. 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, as well as improving validated questionnaire scores monitoring symptom burden and disability. However, neither IVIG nor any other immunosuppressant has been studied in a sufficiently powered and adequately dosed controlled, randomized clinical trial to demonstrate efficacy.

Study Type

Interventional

Enrollment (Estimated)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Recruiting
        • Henry Ford Health
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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, and using Corinthian Reference Laboratory (Benbrook, TX).
  3. Patients must have elevated and/or abnormal titers of autoantibodies to TS-HDS-IgM or FGFR3-IgG or Plexin-D1, measured by the Washington University Neuromuscular Laboratory (St Louis) within 12 months of study 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

Exclusion Criteria:

  1. Any other known cause for small fiber neuropathy other than the presence of the elevated titers of the novel auto-antibodies.
  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, 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 or unwilling to understand or comply with the study protocol

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (IVIG)
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).
Drug: Panzyga IVIG
Immune Globulin Infusion 10% (Human)
Placebo Comparator: Placebo
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).
Drug: Placebo
0.9% NaCl prepared as the calculated dose equivalent volume to IVIG.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
quantified change in intraepidermal nerve fiber density (IENFD)
Time Frame: Week 24
3mm skin punch biopsy at 3 sites
Week 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in visual analogue pain scale responses
Time Frame: baseline and Week 28
Self-reported pain intensity on a scale of 0-10 using the Wong-Baker FACES Pain Rating Scale, with 0 being no pain and 10 being pain as bad as can be
baseline and Week 28
Change in Small Fiber Neuropathy-Rasch Overall Disability Scale (SFN-RODS) score
Time Frame: baseline and Week 28
The SFN-RODS is a 32-item scale measuring disability in daily activities. Scores range from 0 - 64, with a lower score correlating with worse disease
baseline and Week 28
Change in Small Fiber Neuropathy-Symptom Inventory Questionnaire (SFN-SIQ) score
Time Frame: baseline and Week 28
The SFN-SIQ is a validated 13-item scale measuring various SFN and autonomic symptoms. Scores range from 0 -39, with a higher score correlating with more severe disease.
baseline and Week 28
Change in Utah Early Neuropathy Scale (UENS) examination scores
Time Frame: baseline and Week 28
The UENS is a validated physical exam score from 0-42 points to look for small fiber neuropathy. It includes measures of sensation, reflexes, and strength in both lower extremities. A higher score indicates increased impairment.
baseline and Week 28

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Henry Ford Health System

Collaborators

Octapharma USA, Inc.

Investigators

  • Principal Investigator: Lawrence Zeidman, MD, FAAN, Henry Ford Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 15, 2023

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

April 1, 2027

Study Registration Dates

First Submitted

November 4, 2019

First Submitted That Met QC Criteria

November 4, 2019

First Posted (Actual)

November 6, 2019

Study Record Updates

Last Update Posted (Actual)

January 12, 2024

Last Update Submitted That Met QC Criteria

January 11, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 212029

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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