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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

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

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

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

Time Frame

baseline and Week 28

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

kswiftn1@hfhs.org

First Name & Middle Initial & Last Name or Official Title & Degree

Kelly Tundo, RN

Phone

313-916-1102

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

lzeidma1@hfhs.org

12. IPD Sharing Statement

Plan to Share IPD

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

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