Predictive Analytics for Theranosis in RA (PAnTheRA)

• ClinicalTrials.gov Identifier: NCT02928276
• Recruitment Status: Recruiting
• First Posted: October 10, 2016
• Last Update Posted: February 7, 2019
• Sponsor: DNAlytics
• Collaborator: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
• Information provided by (Responsible Party): DNAlytics

Study Description

Brief Summary:

RA is the most common inflammatory, persistent and progressive disease of the joints with serious co-morbidities and huge health and socio-economic impact worldwide.

Condition or disease	Intervention/treatment	Phase
Rheumatoid Arthritis	Other: RheumaKit: Prediction of the response to anti-TNFs DMARDs	Not Applicable

Detailed Description:

The current standard therapeutic strategy for RA patients is to initiate a DMARDs therapy, (e.g. MTX) with serious side effects. This also applies to some PSO or SNSA patients. MTX is however inefficient in about 40% of the cases. Other treatments (biological DMARDs) must thus be initiated, which have an overall similar effectiveness and side effects and an higher cost (around 13kEUR/year/patient). Therapeutic choices are based on symptoms and blood tests including markers of inflammation which are inadequate to predict disease evolution and response to treatments. Improving RA management requires to improve the adequacy of the therapeutic strategies. The earlier the disease is correctly addressed, the more likely its progression and irreversible damages to the joints will be limited. DNAlytics recently developed RheumaKit a differential diagnostic solution for UA patients. UA is a condition in which joint inflammation is present, but a precise diagnosis cannot be made, due to the lack of sensitivity of presently available diagnostic techniques. RheumaKit is a multi-gene expression solution that discriminates RA from other joint conditions. A diagnostic model train to identify patients suffering from RA, SNSA or OA. RheumaKit diagnostic accuracy is higher than 90%, a performance that is better than any other diagnostic solution designed until now, including the ACR/EULAR 2010 criteria for the diagnosis of RA. See working principle below. Beyond diagnosis, DNAlytics wants to make RheumaKit evolve towards treatment recommendation applications (theranostic applications) for patients eligible for biological DMARDs. On one hand, the diseases of these patients have been more and more described in terms of the activity of several metabolic pathways (T & B cells activation, Extra cellular matrix, Inteferon, TNF). On the other hand, the existing treatments also have been more and more described in terms of the pathways they target. The RheumaKit signature contains many markers that are representative of these pathways of interest. RheumaKit thus now provides a snapshot of the activity of seven metabolic pathways known from literature to be related to diseases mechanisms, or to be target of existing treatments. In this study, DNAlytics wants to show that based on a score defined on the RheumaKit platform, the response or non- response to anti-TNFs, representing the largest category of biological DMARDs, can be predicted before treatment initiation.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 110 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Prediction of the Response to Anti-TNFs DMARDs Based on the RheumaKit ® Platform (RK-Tx-01)
• Study Start Date: November 2016
• Estimated Primary Completion Date: December 2019
• Estimated Study Completion Date: April 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: All patients; All eligible patients	Other: RheumaKit: Prediction of the response to anti-TNFs DMARDs

Outcome Measures

Primary Outcome Measures :

1. Ability of a score [ Time Frame: Up to 12 months ]
   To show the ability of a score, computed prior to treatment initiation, to be predictive of the individual anti-TNF response. The score is based on the RheumaKit transcriptomic profiles from a set of small synovial biopsies from a given joint also harvested before anti-TNF treatment initiation.

Secondary Outcome Measures :

1. Identify additional/alternative mappings [ Time Frame: Up to 12 months ]
   To identify additional/alternative mappings between components of gene expression profiles obtained via the RheumaKit assay (extended, and possibly combined to clinical and biological information) and efficacy of anti-TNFs biological DMARDs.
2. Validate the sample logistics at an international scale. [ Time Frame: Up to 12 months ]
   To validate the feasibility of the implementation of a molecular biology test in rheumatology based on synovial tissue at an international scale. This covers both logistics and patient agreeableness aspects.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Patients must satisfy all of the following criteria:

• Signed the ICF and covered by health insurance.
• At least 18 years old.
• For women, use of a reliable method of birth control or remain abstinent during the study, or have had surgical sterilization or women above 60 years of age.
• Having undergone at least 3 months of synthetic DMARD treatment while being strictly eligible for it (diagnosed with RA) and being at a stable dose at least for the last month, and showing no satisfactory response to this therapy.
• Be eligible for biological DMARD treatment according to local regulation and practice.
• Willing and able to comply with scheduled visits, treatment plan, tests and other protocol procedures.

Exclusion Criteria:

Patients must satisfy none of the following criteria:

• Arthritis history longer than 5 years.
• Biological DMARD therapy already initiated.
• Be diagnosed with septic arthritis.
• Be pregnant or breastfeeding/lactating women.
• Diagnosed with HIV, hepatitis B, hepatitis C, Crohn's disease, fibromyalgia.
• Diagnosed with other inflammatory arthritic syndrome than RA.
• have a chronic pain condition that would confound evaluation of the patient.
• Be identified as at too high risk for biopsy or for biologic therapy.
• Be identified as having psychological, familial, social or geographical conditions which could potentially hamper compliance with the study protocol and follow-up schedule.

Contacts and Locations

Contacts

Contact: Helleputte Thibault, PhD; +32 10 39 00 96; thibault.helleputte@dnalytics.com

Locations

Belgium

Clinique Universitaires Saint-Luc; Recruiting

Brussels, Bruxelles-capital, Belgium, 1200

Contact: Aurore Maboge, MSc +32 2 764 79 80 aurore.maboge@uclouvain.be

Principal Investigator: Patrick Durez, MD, PhD

Sub-Investigator: Bernard Lauwerys, MD, PhD

CHU Saint-Pierre; Recruiting

Bruxelles, Belgium, 1000

Contact: Katty Renard, MSc + 32.2.535.48.56 katty_renard@stpierre-bru.be

Principal Investigator: Laurent Méric de Bellfon, MD

Sub-Investigator: Silvana Di Romana, MD

UZLeuven, Gasthuisberg; Recruiting

Leuven, Belgium, 3000

Contact: Johan Joly johan.joly@uzleuven.be

Principal Investigator: Rene Westhovens, MD, PhD

Principal Investigator: Patrick Verschueren, MD, PhD

CHU Liège; Recruiting

Liège, Belgium

Contact: Anja Volders avolders@chu.ulg.ac.be

Principal Investigator: Michel Malaise, MD, PhD

Spain

Parc Taulí Hospital Universitari; Recruiting

Sabadell, Catalunia, Spain, 08208

Contact: Lorena Blanco lblanco@tauli.cat

Principal Investigator: Eduard Graell, MD

Sub-Investigator: Antonio D Gomez, MD

Sponsors and Collaborators

DNAlytics

Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Investigators

• Principal Investigator: Patrick Durez, MD, PhD; Clinique Universitaire Saint-Luc

More Information

Publications:

Lauwerys BR, Hernández-Lobato D, Gramme P, Ducreux J, Dessy A, Focant I, Ambroise J, Bearzatto B, Nzeusseu Toukap A, Van den Eynde BJ, Elewaut D, Gala JL, Durez P, Houssiau FA, Helleputte T, Dupont P. Heterogeneity of synovial molecular patterns in patients with arthritis. PLoS One. 2015 Apr 30;10(4):e0122104. doi: 10.1371/journal.pone.0122104. eCollection 2015.

• Responsible Party: DNAlytics
• ClinicalTrials.gov Identifier: NCT02928276
• Other Study ID Numbers: RK-Tx-01
• First Posted: October 10, 2016
• Last Update Posted: February 7, 2019
• Last Verified: February 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by DNAlytics:

Rheumakit; Rheumatoid Arthritis; anti-TNF

Additional relevant MeSH terms:

Arthritis; Arthritis, Rheumatoid; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases