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

Sponsor
Loyola University (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT04153422
Collaborator
Octapharma USA, Inc. (Other)
20
Enrollment
1
Location
2
Arms
39
Anticipated Duration (Months)
0.5
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Panzyga IVIG
  • Drug: Placebo
 Phase 2

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 up to 19% 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. 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 Design

Study Type:
Interventional
Anticipated Enrollment :
20 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
This is a randomized, double-blind, placebo-controlled study with 10 patients in the treatment arm and 10 in the placebo arm. 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). 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)).This is a randomized, double-blind, placebo-controlled study with 10 patients in the treatment arm and 10 in the placebo arm. 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). 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)).
Masking:
Double (Participant, Investigator)
Masking Description:
This is a double-blind trial. The participant and the investigator will be masked to the treatment assignment.
Primary Purpose:
Treatment
Official Title:
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
Anticipated Study Start Date :
Oct 1, 2022
Anticipated Primary Completion Date :
Jun 30, 2025
Anticipated Study Completion Date :
Dec 31, 2025

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

  1. quantified change in intraepidermal nerve fiber density (IENFD) [Week 24]

    3mm skin punch biopsy at 3 sites

Secondary Outcome Measures

  1. Change in visual analogue pain scale responses [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

  2. Change in Small Fiber Neuropathy-Rasch Overall Disability Scale (SFN-RODS) score [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

  3. Change in Small Fiber Neuropathy-Symptom Inventory Questionnaire (SFN-SIQ) score [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.

  4. Change in Utah Early Neuropathy Scale (UENS) examination scores [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

  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).

  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. 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)

  4. 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.

  5. Known significant IgA deficiency with antibodies to IgA.

  6. History of hypersensitivity, anaphylaxis or severe systemic response to immuno-globulin, blood or plasma derived products, or any component of IVIG 10%,

  7. Known blood hyperviscosity, or other hypercoagulable states,

  8. Use of IgG products within six months prior to enrollment,

  9. Patients with a history of drug or alcohol abuse within the past five years prior to enrollment,

  10. Patients unable or unwilling to understand or comply with the study protocol

Contacts and Locations

Locations

Site City State Country Postal Code
1 Northwest Community Healthcare Arlington Heights Illinois United States 60005

Sponsors and Collaborators

  • Loyola University
  • Octapharma USA, Inc.

Investigators

  • Principal Investigator: Lawrence Zeidman, MD, FAAN, Northwest Community Healthcare, Division of Neurosciences, Northshore University HealthSystem

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Lawrence Zeidman, Medical Director, Neuromuscular Medicine, Northwest Community Healthcare; Associate Professor, Loyola University
ClinicalTrials.gov Identifier:
NCT04153422
Other Study ID Numbers:
  • 212029
First Posted:
Nov 6, 2019
Last Update Posted:
Aug 25, 2022
Last Verified:
Aug 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
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
Keywords provided by Lawrence Zeidman, Medical Director, Neuromuscular Medicine, Northwest Community Healthcare; Associate Professor, Loyola University
Small Fiber Neuropathy
Neuropathy
Intravenous Immunoglobulin
IVIG
TS-HDS antibody
FGFR-3 antibody
FGFR3 antibody
Immune mediated small fiber neuropathy
Panzyga
Additional relevant MeSH terms:
Peripheral Nervous System Diseases
Polyneuropathies
Small Fiber Neuropathy

Study Results

No Results Posted as of Aug 25, 2022