NCT05659407

Brief Summary

A variant of the TNFSF13B gene, commonly referred to as BAFF-var has been associated with an increased risk of developing immune-mediated diseases, such as Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA). This polymorphism leads to the production of higher levels of BAFFs, that in turns are associated with more severe disease, high anti-Sm and anti-dsDNA titre, complement consumption, and increased risk of flare in SLE, and higher disease activity in RA. This is a prospective study aiming to explore the immunological basis of a potential role of BAFF-var as a prognostic biomarker for response to belimumab and rituximab, the main B-depletive treatments, in SLE and RA patients, respectively. More in detail, the study aims to evaluate if the condition of BAFF-var carrier in SLE and RA patients, treated respectively, with belimumab plus standard of care or rituximab influences immunological, molecular and clinical variables, such as: (a) soluble BAFF (BAFFs) cytokine, (b) mRNA-BAFF (c) miRNA-15a (d) B-cell subpopulations (d) disease activity, as assessed by standardized clinimetric tools.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
60

participants targeted

Target at P25-P50 for all trials

Timeline
Completed

Started Jul 2020

Typical duration for all trials

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 24, 2020

Completed
2.4 years until next milestone

First Submitted

Initial submission to the registry

December 13, 2022

Completed
8 days until next milestone

First Posted

Study publicly available on registry

December 21, 2022

Completed
1 month until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 31, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 31, 2023

Completed
Last Updated

December 21, 2022

Status Verified

December 1, 2022

Enrollment Period

2.5 years

First QC Date

December 13, 2022

Last Update Submit

December 13, 2022

Conditions

Systemic Lupus ErythematosusRheumatoid ArthritisBLyS Polymorphism

Keywords

Systemic lupus ErythematosusRheumatoid ArthritisBLyS PolymorphismBelimumabRituximab

Outcome Measures

Primary Outcomes (3)

  • BAFFs

    Comparison of BAFFs level before and after treatment in BAFF-var carrier and no BAFF-var carrier

    12 months

  • mRNA-BAFF e miRNA-15a

    Comparison of mRNA-BAFF e miRNA-15a levels before and after treatment in BAFF-var carrier and no BAFF-var carrier

    12 months

  • B-cell subpopulations

    B-cell phenotyping before and after treatment in BAFF-var carrier and no BAFF-var carrier

    12 months

Secondary Outcomes (6)

  • Delta PGA in SLE patients

    12 months

  • SLE responder index (SRI) in SLE patients

    12 months

  • Achievement of clinical remission ins SLE patients

    12 months

  • Delta PGA in RA patients

    12 months

  • Delta DAS-28 in RA patients

    12 months

  • +1 more secondary outcomes

Study Arms (2)

BAFF-var carrier

Drug: Belimumab in SLE patients / Rituximab in RA patients

No BAFF-var carrier

Drug: Belimumab in SLE patients / Rituximab in RA patients

Interventions

Belimumab in SLE patients / Rituximab in RA patientsDRUG

Belimumab and Rituximab are the the investigated treatments, respectively in the SLE and RA group. They are administrated according to the approved indications and in compliance with the current recommendations and the good clinical practice, independently to the aim of the present observational study.

BAFF-var carrierNo BAFF-var carrier

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

A real-life monocentric cohort of consecutive patients affected by SLE and RA (recruited in the Rheumatology Unit, University Clinic of Cagliari), who started treatment with, respectively, belimumab or rituximab at the enrollment.

You may qualify if:

  • Age ≥18 years
  • SLE diagnosis according to the '97 ACR Criteria / RA diagnosis to the ACR/EULAR 2010 criteria
  • Belimumab / Rituximab initiation at the enrollment, according to the product indications.
  • Treatment with glucocorticoids stable over the previous 4 weeks
  • Treatment with other immunosuppressant stable over the previous 12 weeks

You may not qualify if:

  • Age \< 18 years

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Matteo Piga

Monserrato, Cagliari, 09042, Italy

RECRUITING

Related Publications (7)

  • Vincent FB, Morand EF, Schneider P, Mackay F. The BAFF/APRIL system in SLE pathogenesis. Nat Rev Rheumatol. 2014 Jun;10(6):365-73. doi: 10.1038/nrrheum.2014.33. Epub 2014 Mar 11.

    PMID: 24614588BACKGROUND

  • Wei F, Chang Y, Wei W. The role of BAFF in the progression of rheumatoid arthritis. Cytokine. 2015 Dec;76(2):537-544. doi: 10.1016/j.cyto.2015.07.014. Epub 2015 Jul 18.

    PMID: 26198030BACKGROUND

  • Petri MA, van Vollenhoven RF, Buyon J, Levy RA, Navarra SV, Cervera R, Zhong ZJ, Freimuth WW; BLISS-52 and BLISS-76 Study Groups. Baseline predictors of systemic lupus erythematosus flares: data from the combined placebo groups in the phase III belimumab trials. Arthritis Rheum. 2013 Aug;65(8):2143-53. doi: 10.1002/art.37995.

    PMID: 23754628BACKGROUND

  • Petri M, Stohl W, Chatham W, McCune WJ, Chevrier M, Ryel J, Recta V, Zhong J, Freimuth W. Association of plasma B lymphocyte stimulator levels and disease activity in systemic lupus erythematosus. Arthritis Rheum. 2008 Aug;58(8):2453-9. doi: 10.1002/art.23678.

    PMID: 18668552BACKGROUND

  • Manzi S, Sanchez-Guerrero J, Merrill JT, Furie R, Gladman D, Navarra SV, Ginzler EM, D'Cruz DP, Doria A, Cooper S, Zhong ZJ, Hough D, Freimuth W, Petri MA; BLISS-52 and BLISS-76 Study Groups. Effects of belimumab, a B lymphocyte stimulator-specific inhibitor, on disease activity across multiple organ domains in patients with systemic lupus erythematosus: combined results from two phase III trials. Ann Rheum Dis. 2012 Nov;71(11):1833-8. doi: 10.1136/annrheumdis-2011-200831. Epub 2012 May 1.

    PMID: 22550315BACKGROUND

  • Cohen SB, Emery P, Greenwald MW, Dougados M, Furie RA, Genovese MC, Keystone EC, Loveless JE, Burmester GR, Cravets MW, Hessey EW, Shaw T, Totoritis MC; REFLEX Trial Group. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: Results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum. 2006 Sep;54(9):2793-806. doi: 10.1002/art.22025.

    PMID: 16947627BACKGROUND

  • Steri M, Orru V, Idda ML, Pitzalis M, Pala M, Zara I, Sidore C, Faa V, Floris M, Deiana M, Asunis I, Porcu E, Mulas A, Piras MG, Lobina M, Lai S, Marongiu M, Serra V, Marongiu M, Sole G, Busonero F, Maschio A, Cusano R, Cuccuru G, Deidda F, Poddie F, Farina G, Dei M, Virdis F, Olla S, Satta MA, Pani M, Delitala A, Cocco E, Frau J, Coghe G, Lorefice L, Fenu G, Ferrigno P, Ban M, Barizzone N, Leone M, Guerini FR, Piga M, Firinu D, Kockum I, Lima Bomfim I, Olsson T, Alfredsson L, Suarez A, Carreira PE, Castillo-Palma MJ, Marcus JH, Congia M, Angius A, Melis M, Gonzalez A, Alarcon Riquelme ME, da Silva BM, Marchini M, Danieli MG, Del Giacco S, Mathieu A, Pani A, Montgomery SB, Rosati G, Hillert J, Sawcer S, D'Alfonso S, Todd JA, Novembre J, Abecasis GR, Whalen MB, Marrosu MG, Meloni A, Sanna S, Gorospe M, Schlessinger D, Fiorillo E, Zoledziewska M, Cucca F. Overexpression of the Cytokine BAFF and Autoimmunity Risk. N Engl J Med. 2017 Apr 27;376(17):1615-1626. doi: 10.1056/NEJMoa1610528.

    PMID: 28445677BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

For BAFF genotyping, whole blood samples will be collected in EDTA at the enrollment. The gDNA will be extracted by the salting-out method according to standard protocol. Customs TaqMan assay specifically designed to genotype the BAFF variants of interest will be used with allele-specific Real Time PCR in all samples.

MeSH Terms

Conditions

Lupus Erythematosus, SystemicArthritis, Rheumatoid

Interventions

belimumabRituximab

Condition Hierarchy (Ancestors)

Connective Tissue DiseasesSkin and Connective Tissue DiseasesAutoimmune DiseasesImmune System DiseasesArthritisJoint DiseasesMusculoskeletal DiseasesRheumatic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Central Study Contacts

Matteo Piga, Prof

CONTACT

+39(0)70 - 675.406matteopiga@unica.it

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Prof.

Study Record Dates

First Submitted

December 13, 2022

First Posted

December 21, 2022

Study Start

July 24, 2020

Primary Completion

January 31, 2023

Study Completion

January 31, 2023

Last Updated

December 21, 2022

Record last verified: 2022-12

Data Sharing

IPD Sharing
Will not share

Locations

IT(1)