IVIG in the Treatment of Autoimmune Small Fiber Neuropathy With TS-HDS, FGFR-3, or Plexin D1 Antibodies
Primary Purpose
Small Fiber Neuropathy, Autoimmune Small Fiber Neuropathy, Inflammatory Polyneuropathy
Status
Not yet recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Panzyga IVIG
Placebo
Sponsored by
![Henry Ford Health System](https://trials-media.s3.amazonaws.com/orgs/henry-ford-health-system.jpeg)
About this trial
This is an interventional treatment trial for Small Fiber Neuropathy focused on measuring Small Fiber Neuropathy, Neuropathy, Intravenous Immunoglobulin, IVIG, TS-HDS antibody, FGFR-3 antibody, FGFR3 antibody, Immune mediated small fiber neuropathy, Panzyga, Plexin D1 antibody
Eligibility Criteria
Inclusion Criteria:
- Patients ≥ age 18
- 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.
- 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).
- Patients must have a baseline pain score on a visual analogue scale (VAS) of Greater or equal to 4/10
- Patients must have a baseline Utah Early Neuropathy Scale (UENS) score of Greater or equal to 4/10
- Small Fiber Neuropathy Screening List (SFNSL) score of 11/84 or greater
- Non-pregnant, non-lactating female
Exclusion Criteria:
- Any other known cause for small fiber neuropathy other than the presence of the elevated titers of the novel auto-antibodies.
- Patients with generalized, severe musculoskeletal conditions other than SFN that prevent a sufficient assessment of the patient by the physician.
- 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)
- 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.
- Known significant IgA deficiency with antibodies to IgA.
- History of hypersensitivity, anaphylaxis or severe systemic response to immuno-globulin, blood or plasma derived products, or any component of IVIG 10%,
- Known blood hyperviscosity, or other hypercoagulable states,
- Use of IgG products within six months prior to enrollment,
- Patients with a history of drug or alcohol abuse within the past five years prior to enrollment,
- Patients unable or unwilling to understand or comply with the study protocol
Sites / Locations
- Henry Ford Health
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Treatment (IVIG)
Placebo
Arm Description
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).
Outcomes
Primary Outcome Measures
quantified change in intraepidermal nerve fiber density (IENFD)
3mm skin punch biopsy at 3 sites
Secondary Outcome Measures
Change in visual analogue pain scale responses
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
Change in Small Fiber Neuropathy-Rasch Overall Disability Scale (SFN-RODS) score
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
Change in Small Fiber Neuropathy-Symptom Inventory Questionnaire (SFN-SIQ) score
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.
Change in Utah Early Neuropathy Scale (UENS) examination scores
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.
Full Information
NCT ID
NCT04153422
First Posted
November 4, 2019
Last Updated
October 3, 2023
Sponsor
Henry Ford Health System
Collaborators
Octapharma USA, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04153422
Brief Title
IVIG in the Treatment of Autoimmune Small Fiber Neuropathy With TS-HDS, FGFR-3, or Plexin D1 Antibodies
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 2023 (Anticipated)
Primary Completion Date
September 2026 (Anticipated)
Study Completion Date
March 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Henry Ford Health System
Collaborators
Octapharma USA, Inc.
4. Oversight
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
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Small Fiber Neuropathy, Autoimmune Small Fiber Neuropathy, Inflammatory Polyneuropathy, Immune-Mediated Neuropathy
Keywords
Small Fiber Neuropathy, Neuropathy, Intravenous Immunoglobulin, IVIG, TS-HDS antibody, FGFR-3 antibody, FGFR3 antibody, Immune mediated small fiber neuropathy, Panzyga, Plexin D1 antibody
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
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)).
Masking
ParticipantInvestigator
Masking Description
This is a double-blind trial. The participant and the investigator will be masked to the treatment assignment.
Allocation
Randomized
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment (IVIG)
Arm Type
Experimental
Arm Description
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).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Panzyga IVIG
Intervention Description
Immune Globulin Infusion 10% (Human)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
0.9% NaCl prepared as the calculated dose equivalent volume to IVIG.
Primary Outcome Measure Information:
Title
quantified change in intraepidermal nerve fiber density (IENFD)
Description
3mm skin punch biopsy at 3 sites
Time Frame
Week 24
Secondary Outcome Measure Information:
Title
Change in visual analogue pain scale responses
Description
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
Time Frame
baseline and Week 28
Title
Change in Small Fiber Neuropathy-Rasch Overall Disability Scale (SFN-RODS) score
Description
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
Time Frame
baseline and Week 28
Title
Change in Small Fiber Neuropathy-Symptom Inventory Questionnaire (SFN-SIQ) score
Description
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.
Time Frame
baseline and Week 28
Title
Change in Utah Early Neuropathy Scale (UENS) examination scores
Description
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.
Time Frame
baseline and Week 28
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients ≥ age 18
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).
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).
Patients must have a baseline pain score on a visual analogue scale (VAS) of Greater or equal to 4/10
Patients must have a baseline Utah Early Neuropathy Scale (UENS) score of Greater or equal to 4/10
Small Fiber Neuropathy Screening List (SFNSL) score of 11/84 or greater
Non-pregnant, non-lactating female
Exclusion Criteria:
Any other known cause for small fiber neuropathy other than the presence of the elevated titers of the novel auto-antibodies.
Patients with generalized, severe musculoskeletal conditions other than SFN that prevent a sufficient assessment of the patient by the physician.
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)
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.
Known significant IgA deficiency with antibodies to IgA.
History of hypersensitivity, anaphylaxis or severe systemic response to immuno-globulin, blood or plasma derived products, or any component of IVIG 10%,
Known blood hyperviscosity, or other hypercoagulable states,
Use of IgG products within six months prior to enrollment,
Patients with a history of drug or alcohol abuse within the past five years prior to enrollment,
Patients unable or unwilling to understand or comply with the study protocol
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kate Swiftney, RN
Phone
313-916-3501
Email
kswiftn1@hfhs.org
First Name & Middle Initial & Last Name or Official Title & Degree
Kelly Tundo, RN
Phone
313-916-1102
Email
kciach1@hfhs.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lawrence Zeidman, MD, FAAN
Organizational Affiliation
Henry Ford Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
Henry Ford Health
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lawrence Zeidman, MD, FAAN
Email
lzeidma1@hfhs.org
12. IPD Sharing Statement
Plan to Share IPD
No
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Learn more about this trial
IVIG in the Treatment of Autoimmune Small Fiber Neuropathy With TS-HDS, FGFR-3, or Plexin D1 Antibodies
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