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NEw Clinical Endpoints in primary Sjögren’s Syndrome: an Interventional Trial based on stratifYing patients

Project description

Novel biomarkers for stratifying patients with primary Sjögren’s syndrome

Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease (AID) presenting with heterogeneous clinical manifestations and biological disturbances. It primarily affects exocrine glands leading to dryness of the eyes and the mouth, but it can also cause kidney or lung disease. The multi-organ impact of pSS has hampered drug discovery with only one licensed drug in the last 20 years. Scientists of the EU-funded NECESSITY project will assist in drug-discovery efforts by determining sensitive clinical endpoints, for use in future clinical trials involving patients with pSS. Through a clinical trial, they will evaluate these endpoints alongside discriminative biomarkers for the stratification of patients with pSS.

Objective

Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease (AID) involving 0.5 to 3/1000 persons. The disease affects exocrine glands leading to dryness of the eyes and the mouth and is associated with fatigue and limb pain. In 30% to 50% of the patients, systemic and extra-glandular manifestations may develop. The spectrum of extra-glandular manifestations in pSS is broad and includes vasculitis, peripheral neuropathy, synovitis, kidney involvement and interstitial lung disease. Moreover, pSS patients have a 10 to 20-fold higher risk of developing B cell lymphomas, conferring shorter lifetime expectancy to these patients.
Whereas 10 new targeted-immunomodulatory treatments have been marketed for rheumatoid arthritis in the past 20 years, only one drug has been licensed for other systemic AIDs, such as pSS and systemic erythematous lupus in the same period. There are several factors that may hamper the development of successful drugs for AID. Being multi-organ, these AIDs are considerably heterogeneous among individuals both in terms of clinical manifestations and biological disturbances, with, as a consequence, a great difficulty to set-up accurate composite clinical end-points sensitive to change and usable in clinical trials. In this project, our objectives are:

• To develop and assess sensitive clinical endpoints, for use in future clinical trials, able to evaluate response to drug treatments in patients with pSS with high disease burden and/or systemic involvement,

• To identify and evaluate discriminative biomarkers for stratification of pSS patients predictive of organ involvement and disease progression and thus available for inclusion in clinical trials,

• To set-up and perform an original multi-arm multi-stage clinical trial to validate the newly defined pSS endpoints and the identified biomarkers, by maximizing the chance of finding a difference between the placebo arm and the treated arm.

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Programme(s)

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Topic(s)

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Funding Scheme

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RIA - Research and Innovation action

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Call for proposal

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(opens in new window) H2020-JTI-IMI2-2017-12-two-stage

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Coordinator

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 575 416,85
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 932 235,61

Participants (28)

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