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Intravenous Immunoglobulins for the Treatment of Primary Sjögren's Syndrome Associated Painful Sensory Neuropathies (TINISS)

Primary Purpose

Primary Sjögren's Syndrome Painful Sensory Neuropathies

Status
Recruiting
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Privigen® 100mg/ml at the dose of 2g/kg of body weight
NaCl 0,9%
Sponsored by
University Hospital, Strasbourg, France
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Sjögren's Syndrome Painful Sensory Neuropathies

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age ≥ 18 years and < 80 years
  • Primary Sjögren's syndrome defined as per the European and American criteria (5)

  • Peripheral neuropathy clinically defined:

    • Pure sensitive (lymph node disease) or sensorimotor neuropathies
    • Proved EMG

  • Renal function, and viral evaluation (VIH and hepatitis serology) :

    *Clairance > 50 (In case of biological abnormality, the second dosage can be scheduled within 2 weeks)

  • Effective contraception during the study period
  • Patient capable of understanding information about the study and of giving his/her consent
  • Patient informed of the preliminary medical exam results
  • Patient with healthcare insurance
  • Written consent signed

Exclusion Criteria:

  • Peripheral neurological damage of the type vascularitis-related multiplex mononeuropathy
  • Small fibers neuropathy
  • Neuropathy suspected of being related to alcohol, diabetes or post-chemotherapy
  • Chronic viral infection (HCV, HBV, HIV, etc.)
  • Prior treatment with polyvalent intravenous immunoglobulins in the 6 months preceding the study
  • Corticosteroid treatment at a dose greater than 20 mg/d of prednisone equivalent or no stable dose for at least 1 month before inclusion
  • Conventional immunosuppressant treatment with azathioprin, cyclophosphamide or mycophenolate mofetil on-going or interrupted less than one month before inclusion
  • Rituximab or other biotherapy (belimumab, tocilizumab, …) less than 6 months before the start of the study treatment
  • Immunomodulating treatment with methotrexate no stable dose for at least 2 months before inclusion
  • Hydroxychloroquine no stable dose for at least 3 months before inclusion
  • Pilocarpine hydrochloride secretagogue treatment no stable dose for at least one month before inclusion
  • Treatment with amitriptyline, clomipramine, carbamazepine, clonazepam, pregabaline, duloxetine or gabapentine if the dose has not been stable for at least one month before inclusion (possible dose reduction to be documented).
  • renal clairance < 50 ml/mn
  • HIV seropositivity
  • HBV, or HCV viral replication
  • Contraindication to the use of IV Ig: h Hypersensitivity to the active substance or to any of the excipients; hypersensitivity to human immunoglobulins, especially in patients with antibodies against IgA; patients with hyperprolinaemia.
  • Contraindication to the use of Nacl
  • Immunization with live attenuated vaccine within 2 weeks prior to inclusion
  • Participation in a clinical study with an investigational product with an exclusion period
  • Women of child bearing potential or intends to become pregnant, unless they are using an effective method of birth control* and a βHCG blood test negative
  • Pregnant or nursing (lactating) women
  • Patient under legal guardianship
  • Prisoners

Sites / Locations

  • University Hospital, Strasbourg, franceRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Privigen

Placebo

Arm Description

TThe treatment (IV Ig, 100mg/ml at the dose of 2g/kg of body weight) will be administered by perfusion every 6 weeks, with a total of 3 perfusions administered (W0, W4, W8).

The treatment (NaCl 0,9% 20 ml/kg) will be administered by perfusion every 4 weeks, with a total of 3 perfusions administered (W0, W4, W8).

Outcomes

Primary Outcome Measures

Improvement of at least 20% over placebo of numerical Pain Scale
Improvement of at least 20% over placebo with the R-DS scale (Rasch-built Overall Disability Scale)

Secondary Outcome Measures

Evaluate patient's quality of life, fatigue, and Sicca syndrome intensity.
o Quality of life scale (SF 36)
Evaluate patient's quality of life, fatigue, and Sicca syndrome intensity.
o HAD depression score
Evaluate patient's quality of life, fatigue, and Sicca syndrome intensity.
o Numerical Fatigue Scale
Evaluate patient's quality of life, fatigue, and Sicca syndrome intensity.
o A fatigue scale (EMIF)
Evaluate patient's quality of life, fatigue, and Sicca syndrome intensity. intensity.
o Numerical Dry mouth Scale
Evaluate patient's quality of life, fatigue, and Sicca syndrome intensity. intensity.
o Numerical Dry eye Scale
Evaluate patient's quality of life, fatigue, and Sicca syndrome intensity.
o ESSPRI
Evaluate patient's quality of life, fatigue, and Sicca syndrome intensity.
o ESSDAI
Evaluate intensity of the IV Ig effect on neurological scales
o Overall Neuropathy Limitations Scale (ONLS)

Full Information

First Posted
August 24, 2018
Last Updated
August 10, 2023
Sponsor
University Hospital, Strasbourg, France
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1. Study Identification

Unique Protocol Identification Number
NCT03700138
Brief Title
Intravenous Immunoglobulins for the Treatment of Primary Sjögren's Syndrome Associated Painful Sensory Neuropathies
Acronym
TINISS
Official Title
Prospective, Randomised, Placebo-controlled Study of Polyvalent Intravenous Immunoglobulins for the Treatment of Primary Sjögren's Syndrome Associated Painful Sensory Neuropathies
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 19, 2019 (Actual)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
July 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Strasbourg, France

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
To summarise, the peripheral neurological complications experienced by patients with primary Sjögren's syndrome are particularly bothersome since they are common and often result in significant disability related to pain or motor impairment. There is currently no standard treatment for these patients. As these neuropathies are caused by an immune system dysfunction, which is related to a variety of different pathogenic mechanisms, the use of immunosuppressant or immunomodulator drugs is often justified. With the exception of the vascularitis-related multiplex mononeuropathies, other pSS-related neuropathies could be suitable candidates for IV Ig treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Sjögren's Syndrome Painful Sensory Neuropathies

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Privigen
Arm Type
Experimental
Arm Description
TThe treatment (IV Ig, 100mg/ml at the dose of 2g/kg of body weight) will be administered by perfusion every 6 weeks, with a total of 3 perfusions administered (W0, W4, W8).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
The treatment (NaCl 0,9% 20 ml/kg) will be administered by perfusion every 4 weeks, with a total of 3 perfusions administered (W0, W4, W8).
Intervention Type
Drug
Intervention Name(s)
Privigen® 100mg/ml at the dose of 2g/kg of body weight
Intervention Description
The treatment (IV Ig, 100mg/ml at the dose of 2g/kg of body weight) will be administered by perfusion every 4 weeks, with a total of 3 perfusions administered (W0, W4, W8).
Intervention Type
Drug
Intervention Name(s)
NaCl 0,9%
Intervention Description
The treatment (NaCl 0,9% 20 ml/kg) will be administered by perfusion every 4 weeks, with a total of 3 perfusions administered (W0, W4, W8).
Primary Outcome Measure Information:
Title
Improvement of at least 20% over placebo of numerical Pain Scale
Time Frame
At week 11
Title
Improvement of at least 20% over placebo with the R-DS scale (Rasch-built Overall Disability Scale)
Time Frame
At week 11
Secondary Outcome Measure Information:
Title
Evaluate patient's quality of life, fatigue, and Sicca syndrome intensity.
Description
o Quality of life scale (SF 36)
Time Frame
Weeks 11
Title
Evaluate patient's quality of life, fatigue, and Sicca syndrome intensity.
Description
o HAD depression score
Time Frame
Weeks 11
Title
Evaluate patient's quality of life, fatigue, and Sicca syndrome intensity.
Description
o Numerical Fatigue Scale
Time Frame
Weeks 11
Title
Evaluate patient's quality of life, fatigue, and Sicca syndrome intensity.
Description
o A fatigue scale (EMIF)
Time Frame
Weeks 11
Title
Evaluate patient's quality of life, fatigue, and Sicca syndrome intensity. intensity.
Description
o Numerical Dry mouth Scale
Time Frame
Weeks 11
Title
Evaluate patient's quality of life, fatigue, and Sicca syndrome intensity. intensity.
Description
o Numerical Dry eye Scale
Time Frame
Weeks11
Title
Evaluate patient's quality of life, fatigue, and Sicca syndrome intensity.
Description
o ESSPRI
Time Frame
Weeks 11
Title
Evaluate patient's quality of life, fatigue, and Sicca syndrome intensity.
Description
o ESSDAI
Time Frame
Weeks 11
Title
Evaluate intensity of the IV Ig effect on neurological scales
Description
o Overall Neuropathy Limitations Scale (ONLS)
Time Frame
Weeks 11

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥ 18 years and < 80 years Primary Sjögren's syndrome defined as per the European and American criteria (5) Peripheral neuropathy clinically defined: Pure sensitive (lymph node disease) or sensorimotor neuropathies Proved EMG Renal function, and viral evaluation (VIH and hepatitis serology) : *Clairance > 50 (In case of biological abnormality, the second dosage can be scheduled within 2 weeks) Effective contraception during the study period Patient capable of understanding information about the study and of giving his/her consent Patient informed of the preliminary medical exam results Patient with healthcare insurance Written consent signed Exclusion Criteria: Peripheral neurological damage of the type vascularitis-related multiplex mononeuropathy Small fibers neuropathy Neuropathy suspected of being related to alcohol, diabetes or post-chemotherapy Chronic viral infection (HCV, HBV, HIV, etc.) Prior treatment with polyvalent intravenous immunoglobulins in the 6 months preceding the study Corticosteroid treatment at a dose greater than 20 mg/d of prednisone equivalent or no stable dose for at least 1 month before inclusion Conventional immunosuppressant treatment with azathioprin, cyclophosphamide or mycophenolate mofetil on-going or interrupted less than one month before inclusion Rituximab or other biotherapy (belimumab, tocilizumab, …) less than 6 months before the start of the study treatment Immunomodulating treatment with methotrexate no stable dose for at least 2 months before inclusion Hydroxychloroquine no stable dose for at least 3 months before inclusion Pilocarpine hydrochloride secretagogue treatment no stable dose for at least one month before inclusion Treatment with amitriptyline, clomipramine, carbamazepine, clonazepam, pregabaline, duloxetine or gabapentine if the dose has not been stable for at least one month before inclusion (possible dose reduction to be documented). renal clairance < 50 ml/mn HIV seropositivity HBV, or HCV viral replication Contraindication to the use of IV Ig: h Hypersensitivity to the active substance or to any of the excipients; hypersensitivity to human immunoglobulins, especially in patients with antibodies against IgA; patients with hyperprolinaemia. Contraindication to the use of Nacl Immunization with live attenuated vaccine within 2 weeks prior to inclusion Participation in a clinical study with an investigational product with an exclusion period Women of child bearing potential or intends to become pregnant, unless they are using an effective method of birth control* and a βHCG blood test negative Pregnant or nursing (lactating) women Patient under legal guardianship Prisoners
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jacques-Eric GOTTENBERG, MD
Phone
03 88 12 79 53
Ext
0033
Email
jacques-eric.gottenberg@chru-strabourg.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Jérôme DE SEZE, MD
Phone
03 88 12 85 43
Ext
0033
Email
Jerome.DESEZE@chru-strasbourg.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jacques-Eric Jacques-Eric, MD
Organizational Affiliation
University Hospital, Strasbourg, France
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital, Strasbourg, france
City
Strasbourg
ZIP/Postal Code
67000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jacques -Eric Gottenberg, MD
Phone
03 88 12 79 53
Ext
0033
Email
jacques-eric.gottenberg@chru-strasbourg.fr

12. IPD Sharing Statement

Learn more about this trial

Intravenous Immunoglobulins for the Treatment of Primary Sjögren's Syndrome Associated Painful Sensory Neuropathies

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