New Clinical End-points in patients with primary Sjögren’s Syndrome: an Interventional Trial based on stratifYing patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20], Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

26 Apr 2022 → ongoing

Decision date (initial)

2024-03-21

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2023-510054-16-00

EudraCT number

2019-002470-32

ClinicalTrials.gov

NCT05113004

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

To evaluate the efficacy of each active treatment combination (hydroxychloroquine + leflunomide and hydroxychloroquine + mycophenolate mofetil) based on proportion of responder patients according to preliminary STAR at week 24 in the pooled cohorts

Conditions and MedDRA coding

Primary Sjogren's syndrome

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Cohort 1 : Having given written informed consent prior to undertaking any study-related procedures
2. Cohort 1 : Patients with pSS according to ACR/EULAR 2016 criteria or AECG 2002 criteria
3. Cohort 1 : With a high level of symptoms (ESSPRI ≥ 5) and low systemic disease activity
4. Cohort 1 : Negative pregnancy test (serum at screening)
5. Cohort 1 : Use highly reliable contraception during study treatment from the screening and for two years after stopping treatment
6. Cohort 2 : Having given written informed consent prior to undertaking any study-related procedures
7. Cohort 2 : Patients with pSS according to ACR/EULAR 2016 criteria or AECG 2002 criteria
8. Cohort 2 : With moderate/high systemic disease activity, as defined by ESSDAI ≥ 5
9. Cohort 2 : Negative pregnancy test (serum at screening)
10. Cohort 2 : Use highly reliable contraception during study treatment from the screening and for two years after stopping treatment

Exclusion criteria 32

1. Age < 18 years
2. Pregnant or breastfeeding women or women wanting to conceive either during or within two years after the end of the treatment period
3. Women of childbearing potential not using highly effective methods of contraception
4. Participation in another interventional trial
5. Contra-indication to HCQ: pre-existing retinopathy, hypersensitivity to HCQ or to any of the excipients of the specialty used
6. Contra-indication to MMF: hypersensitivity to mycophenolate mofetil, acid mycophenolic, mycophenolate sodium or to any of the excipients of the specialty used
7. Contra-indication tor LEF: hypersensitivity to the active substance, the main active metabolite teriflunomide or to any excipients of the specialty used
8. Concomitant treatment with corticosteroids more than 10 mg/day of prednisone equivalent at screening or inclusion (randomisation)
9. Concomitant treatment with other immunomodulators including methotrexate, azathioprine, cyclophosphamide, cyclosporine and tacrolimus
10. Previous treatment with HCQ, LEF, or MMF in the last 3 months
11. Previous treatment with rituximab, other B-cell targeted biologic therapy or cyclophosphamide in the last 6 months
12. 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
13. Severe life-threatening systemic involvement requiring cyclophosphamide or high-dose corticosteroids, or any drug considered as an exclusion criteria
14. Impairment of other severe immunodeficiency states
15. Patients with active malignancy or history of malignancy within the last 5 years except non-melanoma skin cancer
16. Patients with active gastrointestinal tract ulceration, hemorrhage and perforation
17. Patients with history of cardiomyopathy
18. Patients with known hereditary deficiency of hypoxanthine-guanine phosphoribosyl-transferase (HGPRT) such as Lesch-Nyhan and Kelley-Seegmiller syndrome
19. Serious infection in the past month
20. Evidence of active tuberculosis infection
21. Active HCV (positive PCR)
22. Active HBV infection (positivity for HBS antigen, or positivity for anti-HBC antibody without any HBS antigen)
23. HIV infection (positive serology)
24. Positive SARS-Cov2 PCR (if vaccinated for COVID-19, no PCR is required; if history of COVID-19 infection, positive serology is sufficient)
25. Cytopenia defined as neutrophils < 1.0 G/L, lymphocytes < 0.5 G/L, Hb < 10 g/dl or platelets < 100 G/L
26. Moderate to severe renal insufficiency (GFR < 30 ml/min)
27. Severe hypogammaglobulinemia defined as gamma globulins or IgG < 5 g/l
28. Reduced hepatic function: AST or ALT > 2x ULN
29. Prolonged ECG's corrected QT interval (>500 ms)
30. Known history of maculopathy
31. Patients not informed of the risk of alcohol consumption and of the recommendations to avoid alcohol during the entire study
32. Not affiliated to a social security regime (specific for France)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

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

Investigational products

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

Test 3

Placebo 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Coordinator Investigator

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Coordinator Investigator

Third parties 1

Locations

7 EU/EEA countries · 25 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 19 files

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

Application history

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