Prospective, randomised, placebo-controlled study of polyvalent intravenous immunoglobulins for the treatment of primary Sjögren's syndrome associated painful sensory neuropathies

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Les Hopitaux Universitaires De Strasbourg

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10], Diseases [C] - Immune System Diseases [C20]

Trial duration

19 Jun 2019 → 10 Apr 2025

Decision date (initial)

2024-10-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Direction générale de l’offre de soins (DGOS)

External identifiers

EU CT number

2024-517309-95-00

EudraCT number

2017-001371-24

ClinicalTrials.gov

NCT03700138

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

Demonstrate the subjective or objective efficacy of IV Ig in the
treatment of primary Sjögren's syndrome-related peripheral
neuropathies

Secondary objectives 3

1. Evaluate patient's quality of life, fatigue, and Sicca syndrome intensity.
2. To evaluate intensity of the IV Ig effect on neurological scales
3. Evaluate the treatment's safety with regard to patient benefit

Conditions and MedDRA coding

-Peripheral neuropathy clinically defined: *Pure sensitive (lymph node disease) or sensorimotor neuropathies *Proved EMG

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Age ≥ 18 years and < 80 years
2. -Primary Sjögren's syndrome defined as per the European and American criteria
3. -Peripheral neuropathy clinically defined: *Pure sensitive (lymph node disease) or sensorimotor neuropathies *Proved EMG
4. -Renal function, and viral evaluation (VIH and hepatitis serology) : *Clairance > 50 ml/min/1,73m2 (MDRD) (In case of biological abnormality, the second dosage can be scheduled within 2 weeks)
5. -Effective contraception during the study period
6. -Patient capable of understanding information about the study and of giving his/her consent
7. -Patient informed of the preliminary medical exam results
8. Patient with healthcare insurance
9. -Written consent signed

Exclusion criteria 14

1. Peripheral neurological damage of the type vascularitis-related multiplex mononeuropathy
2. Small fibers neuropathy
3. Neuropathy suspected of being related to alcohol, diabetes or postchemotherapy
4. Chronic viral infection (HCV, HBV, HIV, etc.)
5. Concomitant medications : • Prior treatment with polyvalent intravenous immunoglobulins in the 6 months preceding inclusion the study • Conventional immunosuppressant treatment with azathioprin, cyclophosphamide or mycophenolate mofetil on-going or interrupted less than one within one month before inclusion • Rituximab or other biotherapy (belimumab, tocilizumab, …) treatment within 6 months before the start of the study treatment inclusion • Corticosteroid treatment administered at a dose greater than > 20 mg/day of prednisone equivalent or administered at a non-stable dose <20 mg/day within the for at least 1 month before inclusion (Corticosteroid treatment administered at a stable dose < 20 mg/day for at least one month prior to inclusion is allowed) • Immunomodulating treatment with by methotrexate at a non-stable dose within for at least 2 months before inclusion (Immunomudulating treatment by methotrexate given at a stable dose for at least 2 months prior to inclusion is allowed) • Treatment by Hydroxychloroquine at a non-stable dose within for at least 3 months before inclusion (Treatment by Hydroxychloroquine given at a stable dose for at least 3 months prior to inclusion is allowed) • Pilocarpine hydrochloride secretagogue treatment at a non-stable dose within for at least one month before inclusion (Pilocardine hydrochloride secretagogue given at a stable dose for at least one month XML File Identifier: CtM2lMg6Da8T7bFdY61LAfMVsX4= Page 12/27 prior to inclusion is allowed) • Treatment by amitriptyline, clomipramine, carbamazepine, clonazepam, pregabaline, duloxetine or gabapentine at a non-stable dose within if the dose has not been stable for at least one month before inclusion (possible dose reduction to be documented) (Treatment by amitriptyline, clomipramine, carbamazepine, clonazepam, pregabaline, duloxetine or gabapentine given at a stable dose for at least one month prior to inclusion is allowed).
6. Contraindication to the use of IV Ig 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.
7. Contraindication to the use of NaCl
8. Immunization with live attenuated vaccine within 2 weeks prior to inclusion
9. Patients at high risk of thromboembolism and patients with history of thromboembolic event without anticoagulant treatment
10. Participation in a clinical study with an investigational product with an exclusion period
11. 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
12. Pregnant or nursing (lactating) women
13. Patient under legal guardianship
14. Prisoners

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Improvement of at least 20% over placebo in one of the following 2 scales, 3 weeks after the last treatment course (week 11): - Objective neurological criterion using the R-ODS scale (Rasch-built Overall Disability Scale) - Numerical Pain Scale (0 to 10)

Secondary endpoints 3

1. 1) Primary Sjögren's Syndrome Criteria o Quality of life scale (SF 36) o HAD depression score o Numerical Fatigue Scale : score between 0 and 10 o A fatigue scale (EMIF) : o Numerical Dry mouth Scale : score between 0 and 10 o Numerical Dry eye Scale : score between 0 and 10 o Flow of saliva (non stimulated o ESSPRI (Eular Sjogren's Syndrome Patient Reported Index) o ESSDAI (Eular Sjögren Syndrome Disease Activity index)
2. 2) Neurological criteria o Overall Neuropathy Limitations Scale (ONLS)
3. 3) Adverse reactions rate

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Les Hopitaux Universitaires De Strasbourg

Sponsor organisation

Les Hopitaux Universitaires De Strasbourg

Address

1 Place De L Hopital, Cs 80426 Cs 80426

City

Strasbourg Cedex

Postcode

67091

Country

France

Scientific contact point

Organisation

Les Hopitaux Universitaires De Strasbourg

Contact name

Pr Jacques-Eric GOTTENBERG

Public contact point

Organisation

Les Hopitaux Universitaires De Strasbourg

Contact name

Pr Jacques-Eric GOTTENBERG

Locations

1 EU/EEA country · 13 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications