New Clinical End-points in Patients With Primary Sjögren's Syndrome

NCT05113004 | Recruiting Phase 2 DMC

• 1 other identifier: APHP190131
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 7

Brief Summary

There are no approved treatments for pSS and the clinical endpoints currently used in clinical trials are inadequate to capture all aspects of the disease that should be evaluated in clinical trials. The newly developed composite endpoint: Sjögren's Tool for Assessing Response to treatment (STAR) will allow a more specific and meaningful assessment of treatment efficacy in pSS. Because of the heterogeneity of the disease and of the central role of the interplay between B- and T-cells in the pathogenesis, it is worth to evaluate combination of conventional synthetic immunomodulatory drugs targeting both B- and T-cells.

Conditions

Primary Sjögren's Syndrome (pSS)

Keywords

dry eye; Oral Dryness and Saliva Altered; Eular Sjögren Syndrome Disease Activity index; Primary Sjögrens's syndrome

Outcome Measures

Primary Outcomes (2)

• Cohort 1. Proportion of patients achieving a response according to preliminary STAR at week 24 between each active treatment arm and placebo arm.

  During the 24 weeks of the trials

• Cohort 2. Proportion of patients achieving a response according to preliminary STAR at week 24 between each active treatment arm and placebo arm.

  During the 24 weeks of the trials

Study Arms (6)

Arm 1

PLACEBO COMPARATOR

Cohort 1 : Patients with High levels of symptoms and low disease activity receive : Placebo of Leflunomide 20mg/d Placebo of Mycophenolate mofetil 2000mg/d Placebo of hydroxychloroquine 400mg/d

Drug: Placebo of Hydroxychloroquine 400mg/d; Drug: Placebo of Leflunomide 20mg/d; Drug: Placebo of Mycophenolate mofetil 2000mg/d

Arm 2

OTHER

Cohort 1 : Patients with High levels of symptoms and low disease activity receive : Leflunomide 20mg/d hydroxychloroquine 400mg/d Placebo of Mycophenolate mofetil 2000 mg/d

Drug: Hydroxychloroquine 400mg/d; Drug: Leflunomide 20mg/d; Drug: Placebo of Mycophenolate mofetil 2000mg/d

Arm 3

OTHER

Cohort 1 : Patients with High levels of symptoms and low disease activity receive : Placebo of Leflunomide 20mg/d Mycophenolate mofetil 2000mg/d hydroxychloroquine 400mg/d

Drug: Hydroxychloroquine 400mg/d; Drug: Mycophenolate mofetil 2000mg/d; Drug: Placebo of Leflunomide 20mg/d

Arm 4

PLACEBO COMPARATOR

Cohorte 2 :Patients with moderate or hight activity, regardless of level of symptoms, they receive : Placebo of Leflunomide 20mg/d Placebo of Mycophenolate mofetil 2000mg/d Placebo of hydroxychloroquine 400mg/d

Drug: Placebo of Hydroxychloroquine 400mg/d; Drug: Placebo of Leflunomide 20mg/d; Drug: Placebo of Mycophenolate mofetil 2000mg/d

Arm 5

OTHER

Cohorte 2 :Patients with moderate or hight activity, regardless of level of symptoms, they receive : Leflunomide 20mg/d hydroxychloroquine 400mg/d Placebo of Mycophenolate mofetil 2000 mg/d

Drug: Hydroxychloroquine 400mg/d; Drug: Leflunomide 20mg/d; Drug: Placebo of Mycophenolate mofetil 2000mg/d

Arm 6

OTHER

Cohorte 2 :Patients with moderate or hight activity, regardless of level of symptoms, they receive : Placebo of Leflunomide 20mg/d Mycophenolate mofetil 2000mg/d hydroxychloroquine 400mg/d

Drug: Hydroxychloroquine 400mg/d; Drug: Leflunomide 20mg/d; Drug: Placebo of Leflunomide 20mg/d

Interventions

Hydroxychloroquine 400mg/d DRUG

Hydroxychloroquine (HCQ) is a 4-aminoquinoline belonging to the group of antimalarial agents. Its immunomodulatory activity on B-cells has mainly been attributed to its inhibition of antigen presentation, cytokine production, and recently on Toll-like receptor signaling and IFN secretion that drives B cell activation.

Arm 2; Arm 3; Arm 5; Arm 6

Leflunomide 20mg/d DRUG

Leflunomide (LEF) is a derivative of isoxazole and is converted into an active metabolite which blocks de novo synthesis of pyrimidines in activated T lymphocytes, thereby inhibiting T cell proliferation and consequently T cell-dependent B cell formation of autoantibodies.

Arm 2; Arm 5; Arm 6

Mycophenolate mofetil 2000mg/d DRUG

Mycophenolate mofetil (MMF) is a morpholinoethyl ester of mycophenolic acid which blocks proliferation of lymphocytes by inhibiting the de novo pathway of purine biosynthesis (Allison, 2000).

Arm 3

Placebo of Hydroxychloroquine 400mg/d DRUG

Placebo of Hydroxychloroquine (HCQ) is a 4-aminoquinoline belonging to the group of antimalarial agents. Its immunomodulatory activity on B-cells has mainly been attributed to its inhibition of antigen presentation, cytokine production, and recently on Toll-like receptor signaling and IFN secretion that drives B cell activation.

Arm 1; Arm 4

Placebo of Leflunomide 20mg/d DRUG

Placebo of Leflunomide (LEF) is a derivative of isoxazole and is converted into an active metabolite which blocks de novo synthesis of pyrimidines in activated T lymphocytes, thereby inhibiting T cell proliferation

Arm 1; Arm 3; Arm 4; Arm 6

Placebo of Mycophenolate mofetil 2000mg/d DRUG

Placebo of Mycophenolate mofetil (MMF) is a morpholinoethyl ester of mycophenolic acid which blocks proliferation of lymphocytes by inhibiting the de novo pathway of purine biosynthesis (Allison, 2000).

Arm 1; Arm 2; Arm 4; Arm 5

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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 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
• With moderate/high systemic disease activity, as defined by ESSDAI ≥ 5.
• Negative pregnancy test (serum at screening)
• Use highly reliable contraception during research treatment from the screening and for two years after stopping treatment

You may not qualify if:

• 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 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
• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (7)

Valérie Devauchelle

Brest, France

RECRUITING

Eric Hachulla

Lille, 59037, France

RECRUITING

Jacques Morel

Montpellier, 34295, France

RECRUITING

Véronique Le Guern

Paris, 75014, France

RECRUITING

Jacques-Eric Gottenberg

Strasbourg, France

RECRUITING

Christophe Richez

Talence, 33404, France

RECRUITING

Raphaele Seror

Le Kremlin-Bicêtre, Île-de-France Region, France

RECRUITING

MeSH Terms

Conditions

Dry Eye Syndromes; Xerostomia

Interventions

Hydroxychloroquine; Leflunomide; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Lacrimal Apparatus Diseases; Eye Diseases; Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids

Central Study Contacts

Xavier MARIETTE

CONTACT

01.45.21.37.51; xavier.mariette@aphp.fr

Jacques-Eric GOTTENBERG

CONTACT

03 88 12 79 53; jacques-eric.gottenberg@chru-strasbourg.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multi-center, prospective, randomized, double blinded

Study Record Dates

• First Submitted: November 2, 2021
• First Posted: November 9, 2021
• Study Start: January 20, 2022
• Primary Completion: April 1, 2025
• Study Completion: October 1, 2025
• Last Updated: November 1, 2024

Record last verified: 2024-10

Locations

FR (7)