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Rheumatoid ArthritisPhase 3LYRITUXNCT02304354

Relationship Between T LYmphocytes Depletion and Clinical Response to RITUXimab in Rheumatoid Arthritis (LYRITUX)

A Phase 3 study testing Rituximab in people with Rheumatoid Arthritis, run by University Hospital, Tours at 8 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Rituximab, an anti CD-20 monoclonal antibody targeting B lymphocytes is prescribed in rheumatoid arthritis (RA) patients refractory to TNF alpha antagonists. According to previous studies, 25 to 50% of patients have an insufficient or absence of response to rituximab at week 24. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Rheumatoid Arthritis
What is being tested?
Rituximab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
70 participants
Where
8 sitesFrance
Study dates
9 Mar 2015to 18 Dec 2019
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • RA according to the American College of Rheumatology (ACR) criteria
  • Treatment with adalimumab in accordance to the SPC
  • Disease modifying anti rheumatic drugs (DMARDs) stable 4 weeks before enrollment and during 16 weeks.
  • Signed consent

Who cannot join

  • No anti TNF-alpha failure or contraindication
  • Previous adalimumab treatment
  • Contraindication to adalimumab, methylprednisolone or methotrexate (when used in combination with adalimumab)
  • methotrexate-naive patient
  • Any hematologic disease affecting the lymphocytes (in particular lymphomas)
  • Any osteo-articular disease which could interfere with the interpretation of the influence of the rituximab on RA

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

France8 sites

  • Rhumatologie, CHRU de BREST

    Brest, 29609

  • Rhumatologie, CHD LA ROCHE SUR YON

    La Roche-sur-Yon, 85925

  • Rhumatologie, CHR du MANS

    Le Mans, 72037

  • Rhumatologie, CHRU de NANTES

    Nantes, 44093

  • Rhumatologie / IPROS, CHR d'ORLEANS

    Orléans, 45000

  • Rhumatologie, CHRU de POITIERS

    Poitiers, 86021

  • Rhumatologie, CHRU de ROUEN

    Rouen, 76031

  • Rhumatologie, CHRU de TOURS

    Tours, 37044

Other trials in France

About this study

Rituximab, an anti CD-20 monoclonal antibody targeting B lymphocytes is prescribed in rheumatoid arthritis (RA) patients refractory to TNF alpha antagonists. According to previous studies, 25 to 50% of patients have an insufficient or absence of response to rituximab at week 24.

In a recent retrospective study, a CD4+ T-lymphocytes depletion was observed after a first course of rituximab in RA patients. The absolute CD4+ number at week 12 was 37% (±33) of the baseline value, leading to < 200 cells/µL in 5% of patients. Interestingly the absence of CD4+ T-lymphocytes depletion was observed in clinical non-responders, suggesting the involvement of T-lymphocytes in the mechanism of action of rituximab. So far no prospective study have supported the usefulness of lymphocyte phenotyping, in particular T-lymphocytes, to monitor rituximab-treated RA patients.

Read the detailed description

Rituximab, an anti CD-20 monoclonal antibody targeting B lymphocytes is prescribed in rheumatoid arthritis (RA) patients refractory to TNF alpha antagonists. According to previous studies, (Edwards, Szczepanski et al. 2004; Cohen, Emery et al. 2006; Emery, Fleischmann et al. 2006) 25 to 50% of patients have an insufficient or absence of response to rituximab at week 24. In the pathogenesis of RA, B and T lymphocytes are tightly linked through the APC fonction and cytokines production of B lymphocytes. At present, a white blood cells count is recommended in routine every 3 months in patients receiving rituximab, since cases of neutropenia have been observed in approximately 8% of patients with lymphoma after treatment. In RA patients, B lymphocytes count before each rituximab course should be done to prevent opportunistic infections (Pham, Fautrel et al. 2008).

In a recent retrospective study, a CD4+ T-lymphocytes depletion was observed after a first course of rituximab in RA patients. The absolute CD4+ number at week 12 was 37% (±33) of the baseline value, leading to < 200 cells/µL in 5% of patients. Interestingly the absence of CD4+ T-lymphocytes depletion was observed in clinical non-responders, suggesting the involvement of T-lymphocytes in the mechanism of action of rituximab (Mélet, Mulleman et al. 2013). Moreover, few case reports of RA patients developing opportunist infections in conjunction with CD4+ T-lymphocyte depletion have been published (Teichmann, Woenckhaus et al. 2008; Clifford, Ances et al. 2011). So far no prospective study have supported the usefulness of lymphocyte phenotyping, in particular T-lymphocytes, to monitor rituximab-treated RA patients.

Being tested
Rituximab
Keywords
rheumatoid arthritis, T lymphocytes, rituximab
Medical subject headings
Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RituximabDrug

    Also called MabThera

    For rheumatoid arthritis, MabThera is given as two intravenous infusions of 1000 mg with a two-week interval between them. Patients usually respond to treatment within 16 to 24 weeks of initial treatment. After 24 weeks, treatment can be repeated depending on the patient's response.

Study groups in NCT02304354
Study groupRoleWhat they receive
RituximabExperimentaltwo intravenous infusions of 1000 mg with a two-week interval between them
Receives: Drug: Rituximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. DAS28

    Disease Activity Score on 28 joints (DAS28) is a composite score that comprise tender joints count, swollen joints count, patient's disease activity on visual analog scale and erythrocyte sedimentation rate. DAS28 will be measured at baseline, week 2, week 4, week 16 and at the end of the study (i.e. between week 24 and week 48).

    Measured: up week 48

  2. T-lymphocyte count

    T-lymphocyte count will be measured at baseline, week 2, week 4, week 16 and at the end of the study (i.e. between week 24 and week 48).

    Measured: up to week 48

Secondary outcomes (8)

  1. C reactive Protein (CRP)

    CRP will be measured at baseline, week 2, week 4, week 16 and at the end of the study (i.e. between week 24 and week 48).

    Measured: Baseline up to 48 weeks

  2. Immunoglobulines G

    Immunoglobuline G concentrations will be measured at baseline, week 16 and at the end of the study (i.e. between week 24 and week 48).

    Measured: Baseline up to 48 weeks

  3. Cytokine profile

    the following cytokines (APRIL, BAFF, TNF, IL-1 alpha, IL-17 and IL-6) will be measured at baseline, week 2, week 4, week 16 and at the end of the study (i.e. between week 24 and week 48).

    Measured: Baseline up to 48 weeks

  4. Occurrence of infections

    Number of participants with infectious adverse events

    Measured: Baseline up to 48 weeks

  5. Pharmacokinetics (Systemic Clearance and central volume of distribution)

    Rituximab concentrations will be measured at baseline, will be measured at baseline, week 2, week 4, week 16 and at the end of the study (i.e. between week 24 and week 48). Pharmacokinetics will be described using a two-compartment model.

    Measured: Baseline up to 48 weeks

  6. FCGR3A 156 F/V gene polymorphism

    FCGR3A 156 F/V gene genotyping. Measurements will be carried out at baseline.

    Measured: Baseline

  7. RNA

    Gene expression will be analysed at baseline.

    Measured: Baseline

  8. Metabolomic profil

    Urines will be analysed at baseline, week 4 and week 16

    Measured: Baseline up to 16 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Dec 2014 (estimated)
  2. Study start9 Mar 2015
  3. Primary completion9 Apr 2019
  4. Study completion18 Dec 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
70 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02304354
Sponsor's protocol ID
PHRI13-JM/LYRITUX
Other IDs
2014-000859-91, 2014-R24, 140896A-32, 2014
Acronym
LYRITUX
Status last verified
May 2021
First submitted
4 Nov 2014
Last updated
6 May 2021
Results posted
No
Data monitoring committee
No

Publications

  • Melet J, Mulleman D, Goupille P, Ribourtout B, Watier H, Thibault G. Rituximab-induced T cell depletion in patients with rheumatoid arthritis: association with clinical response. Arthritis Rheum. 2013 Nov;65(11):2783-90. doi: 10.1002/art.38107.

    PubMed 23918413

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Rituximab in people with Rheumatoid Arthritis, run by University Hospital, Tours at 8 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

DAS28 (time frame: up week 48). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02304354, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2021.

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