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

Study Overview
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Brief Summary
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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.

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

Conditions
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Primary Sjögren's Syndrome Painful Sensory Neuropathies

Intervention / Treatment
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* Drug: Privigen® 100mg/ml at the dose of 2g/kg of body weight
* Drug: NaCl 0,9%


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Privigen<br>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<br>* 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).<br>|
| Placebo Comparator: Placebo<br>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%<br>* 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).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |