Ew Clinical End-points in patients with primary Sjögren’s Syndrome (pSS): an Interventional Trial based on stratifYing patients

Phase 1

• Conditions: Primary Sjögren’s syndrome (pSS); MedDRA version: 21.0Level: PTClassification code 10040767Term: Sjogren's syndromeSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders; Therapeutic area: Body processes [G] - Immune system processes [G12]

• Registration Number: EUCTR2019-002470-32-NO
• Lead Sponsor: ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS ( AP-HP)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-08-26
• Last Update Posted: 21 May 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

Cohort 1
- Having given written informed consent prior to undertaking any study-related procedures.
- Patients with pSS according to ACR/EULAR 2016 criteria or AECG 2002 criteria (see addenda 4)
- With a high level of symptoms (ESSPRI = 5) and low systemic disease activity (ESSDAI < 5).
- Negative pregnancy test (serum at screening)
- Use highly reliable contraception (as defined in section 6.3) during research treatment from the screening and for two years after stopping treatment.

Cohort 2
- Having given written informed consent prior to undertaking any study-related procedures.
- Patients with pSS according to ACR/EULAR 2016 criteria or AECG 2002 criteria (see addenda 4)
- With moderate/high systemic disease activity, as defined by ESSDAI = 5.
- Negative pregnancy test (serum at screening)
- Use highly reliable contraception (as defined in section 6.3) during research treatment from the screening and for two years after stopping treatment.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 250
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion Criteria

For both cohorts:
- Age < 18 years
- Pregnant or breastfeeding women or women wanted to conceive either during or within two years after the end of the treatment period
- Women of childbearing potential not using highly effective methods of contraception (as defined in section 6.3)
- Participation in another interventional trial
- Contra-indication to HCQ: pre-existing retinopathy, hypersensitivity to HCQ or to any of the excipients of the specialty used
- Contra-indication to MMF: hypersensitivity to mycophenolate mofetil, acid mycophenolic, mycophenolate sodium or to any of the excipients of the specialty used
- Contra-indication tor LEF: hypersensitivity to the active substance, the main active metabolite teriflunomide or to any excipients of the specialty used.
- Concomitant treatment with corticosteroids more than 10 mg/day of prednisone equivalent at screening or inclusion (randomisation)
- Concomitant treatment with other immunomodulators including methotrexate, azathioprine, cyclophosphamide, cyclosporine and tacrolimus
- Previous treatment with HCQ, LEF, MMF in the last 3 months
- Previous treatment with rituximab, other B-cell targeted biologic therapy or cyclophosphamide in the last 6 months
- Previous treatment with anti-TNF, abatacept, tocilizumab or belimumab or any other biologic in the setting of a past clinical trial in the last 3 months
- Severe life-threatening systemic involvement requiring cyclophosphamide or high dose corticosteroids, or any drug considered as an exclusion criteria
- Impairment of other severe immunodeficiency states
- Patients with active malignancy or history of malignancy within the last 5 years except non-melanoma skin cancer
- Patients with history of gastrointestinal tract ulceration, hemorrhage and perforation
- Patients with history of cardiomyopathy
- Patients with known hereditary deficiency of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) such as Lesch-Nyhan and Kelley-Seegmiller syndrome
- Serious infection in the past month
- Evidence of active tuberculosis infection
- Active HCV (positive PCR)
- Active HBV infection (positivity for HBS antigen, or positivity for anti-HBC antibody without any HBS antigen)
- HIV infection (positive serology)
- Positive SARS-Cov2 PCR (if vaccinated for COVID-19, no PCR is required; if history of COVID-19 infection, positive serology is sufficient)
- Cytopenia defined as neutrophils < 1.0 G/L, lymphocytes < 0.5 G/L, Hb < 10 g/dl or platelets < 100 G/L
- Moderate to severe renal insufficiency (GFR < 30 ml/min)
- Severe hypogammaglobulinemia defined as gamma globulins or IgG < 5 g/l
- Reduced hepatic function: AST or ALT > 2x ULN (re-testing is allowed, see section 5.10)
- Prolonged ECG's corrected QT interval (>500 ms)
- Known history of maculopathy
- Patients will be informed of the risk of alcohol consumption and will be recommended to avoid alcohol during the entire study
- Not affiliated to a social security regime (specific for France)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified