Predictive Analytics for Theranosis in RA

Rheumatoid Arthritis Clinical Trial

— PAnTheRA  

Official title:

Prediction of the Response to Anti-TNFs DMARDs Based on the RheumaKit ® Platform (RK-Tx-01)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02928276
• Other study ID #: RK-Tx-01
• Status: Recruiting
• Phase: N/A
• Start date: November 2016
• Est. completion date: April 2020

Study information

• Verified date: February 2019
• Source: DNAlytics
• Contact: Helleputte Thibault, PhD
• Phone: +32 10 39 00 96
• Email: thibault.helleputte[@]dnalytics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 110
• Est. completion date: April 2020
• Est. primary completion date: December 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Other:
• RheumaKit: Prediction of the response to anti-TNFs DMARDs

Locations

Country	Name	City	State
Belgium	Clinique Universitaires Saint-Luc	Brussels	Bruxelles-capital
Belgium	CHU Saint-Pierre	Bruxelles
Belgium	UZLeuven, Gasthuisberg	Leuven
Belgium	CHU Liège	Liège
Spain	Parc Taulí Hospital Universitari	Sabadell	Catalunia

Sponsors (2)

Lead Sponsor	Collaborator
DNAlytics	Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Countries where clinical trial is conducted

Belgium,  Spain, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ability of a score	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.	Up to 12 months
Secondary	Identify additional/alternative mappings	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.	Up to 12 months
Secondary	Validate the sample logistics at an international scale.	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.	Up to 12 months