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

Prospective, Randomised, Placebo-controlled Study of Polyvalent Intravenous Immunoglobulins for the Treatment of Primary Sjögren's Syndrome Associated Painful Sensory Neuropathies

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.

Study Overview

• Status: Completed
• Conditions: Primary Sjögren's Syndrome Painful Sensory Neuropathies
• Intervention / Treatment: Drug: Privigen® 100mg/ml at the dose of 2g/kg of body weight; Drug: NaCl 0,9%

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Strasbourg, France, 67000
    • University Hospital, Strasbourg, france

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Privigen; 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).	Drug: Privigen® 100mg/ml at the dose of 2g/kg of body weight; 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).
Placebo Comparator: Placebo; 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).	Drug: NaCl 0,9%; 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Improvement of at least 20% over placebo of numerical Pain Scale	At week 11
Improvement of at least 20% over placebo with the R-DS scale (Rasch-built Overall Disability Scale)	At week 11

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate patient's quality of life, fatigue, and Sicca syndrome intensity.	o Quality of life scale (SF 36)	Weeks 11
Evaluate patient's quality of life, fatigue, and Sicca syndrome intensity.	o HAD depression score	Weeks 11
Evaluate patient's quality of life, fatigue, and Sicca syndrome intensity.	o Numerical Fatigue Scale	Weeks 11
Evaluate patient's quality of life, fatigue, and Sicca syndrome intensity.	o A fatigue scale (EMIF)	Weeks 11
Evaluate patient's quality of life, fatigue, and Sicca syndrome intensity. intensity.	o Numerical Dry mouth Scale	Weeks 11
Evaluate patient's quality of life, fatigue, and Sicca syndrome intensity. intensity.	o Numerical Dry eye Scale	Weeks11
Evaluate patient's quality of life, fatigue, and Sicca syndrome intensity.	o ESSPRI	Weeks 11
Evaluate patient's quality of life, fatigue, and Sicca syndrome intensity.	o ESSDAI	Weeks 11
Evaluate intensity of the IV Ig effect on neurological scales	o Overall Neuropathy Limitations Scale (ONLS)	Weeks 11

Collaborators and Investigators

• Sponsor: University Hospital, Strasbourg, France
• Investigators: Principal Investigator: Jacques-Eric Jacques-Eric, MD, University Hospital, Strasbourg, france

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2019
• Primary Completion (Actual): April 10, 2025
• Study Completion (Actual): April 10, 2025

Study Registration Dates

• First Submitted: August 24, 2018
• First Submitted That Met QC Criteria: October 8, 2018
• First Posted (Actual): October 9, 2018

Study Record Updates

• Last Update Posted (Actual): August 8, 2025
• Last Update Submitted That Met QC Criteria: August 4, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Musculoskeletal Diseases; Mouth Diseases; Stomatognathic Diseases; Pathologic Processes; Arthritis; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Disease; Eye Diseases; Arthritis, Rheumatoid; Xerostomia; Salivary Gland Diseases; Dry Eye Syndromes; Lacrimal Apparatus Diseases; Pain; Syndrome; Sjogren's Syndrome; Immunologic Factors; Physiological Effects of Drugs; Immunoglobulins, Intravenous
• Other Study ID Numbers: 6621

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No