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Tocilizumab bei chronisch-entzündlicher CPPD-Erkrankung (TociCCAre)

6. November 2026 aktualisiert von: Assistance Publique - Hôpitaux de Paris

Randomisierte, doppelblinde, multizentrische Studie von Tocilizumab versus Placebo bei chronischer polyartikulärer Entzündung durch Calciumpyrophosphat-Ablagerungskrankheit, refraktär gegenüber Standardbehandlungen

The aim of this clinical trial is to determine the efficacy of tocilizumab (an IL-6 inhibitor) in treatment-refractory chronic inflammatory forms of CPPD.

The main questions this trial aims to answer are:

  • Can tocilizumab improve joint pain in patients with chronic inflammatory CPPD disease?
  • Does tocilizumab improve quality of life in patients with chronic inflammatory CPPD disease?

Participants will receive a monthly infusion of tocilizumab or placebo for three months.

Studienübersicht

Status

Noch keine Rekrutierung

Bedingungen

Intervention / Behandlung

Detaillierte Beschreibung

Calcium pyrophosphate deposition (CPPD) disease affects 4 to 7% of the adult population. CPP crystals are responsible for inflammatory flares affecting one or more joints. The inflammation triggered by CPP crystals resembles that associated with sodium urate crystals in gout and depends on inflammatory cytokines such as interleukins (IL-) 1β and -6. The usual treatments are those used in gout flares (colchicine, NSAIDs, corticosteroids, IL-1β inhibitors), and most often control monoarticular involvement. The chronic inflammatory polyarticular form, on the other hand, is more difficult to treat, causing significant pain and disability, as well as joint destruction. In refractory forms, or in cases of intolerance to standard treatments, alternative therapies are required. In this context, the investigators treated 11 patients with refractory chronic inflammatory CPPD with tocilizumab (TCZ), an anti-IL-6 receptor (IL-6R) monoclonal antibody. After 3 monthly infusions, improvement was estimated at over 75% (PMID 2213498). Our hypothesis is that inhibiting IL-6 is an effective therapeutic option in chronic inflammatory CPPD refractory to conventional therapies.

Main objective and primary endpoint:

  • To demonstrate the efficacy of IL-6 inhibition in treatment-refractory chronic inflammatory forms of CPPD disease.
  • Our endpoint will be the change in global pain VAS between initiation and M4, i.e. one month after the 3rd infusion. VAS will be assessed after 24 hours off analgesics.

Secondary objectives and endpoints:

  • Efficacy: DAS28-CRP, number of swollen, painful joints, overall disease activity VAS, fatigue VAS; overall effect on pain: area under the VAS curve (AUC); proportion of patients responding from M2 to M6 (improvement ≥ 50% of initial pain VAS) and complete response (improvement ≥ 80% of initial pain VAS); relapse rate; improvement in quality of life (SF-36, HAQ, EQ-5D-3L questionnaires)
  • Tolerance: infusion reactions, infections, neutropenia, hepatic cytolysis, lipid profile

This is a phase II, multicentre, randomized, controlled, double-blind, superiority study, including 2 parallel groups with a 1:1 distribution. This trial will involve adults suffering from the chronic inflammatory polyarticular form of CPPD disease.

This study will involve 80 participants recruited in 13 centres in France.

Studientyp

Interventionell

Einschreibung (Geschätzt)

80

Phase

  • Phase 2

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienkontakt

Studienorte

  • Frankreich
      • Dijon, Frankreich, 21000
      • Nantes, Frankreich, 44000
      • Paris, Frankreich, 75020
      • Paris, Frankreich, 75020
      • Paris, Frankreich, 93370
        • Groupe Hospitalier Intercommunal Le Raincy-Montfermeil
        • Kontakt:
      • Paris, Frankreich, 94270
        • Hôpital Le Kremlin Bicêtre
      • Paris, Frankreich, 75018
      • Pontoise, Frankreich, 95300
      • Rennes, Frankreich, 35200
      • Saint-Etienne, Frankreich, 42100
    • Lille
      • Lomme, Lille, Frankreich, 59462
        • Groupe Hospitalier de l'Institut Catholique de Lille
        • Kontakt:
    • Paris
      • Corbeil-Essonnes, Paris, Frankreich, 91100
        • Centre Hospitalier Sud-Francilien
        • Kontakt:
    • Paris Paris
      • Paris, Paris Paris, Frankreich, 75010
        • Lariboisière hospital

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

18 Jahre und älter (Erwachsene, Älterer Erwachsener)

Akzeptiert gesunde Freiwillige

Nein

Studienberechtigte Geschlechter

Alle

Beschreibung

Inclusion Criteria:

  • Adults > 18 years
  • Diagnosis of CPPD according to ACR/EULAR 2023 classification criteria
  • Persistent inflammatory pain (> 3 months) or ≥ 2 arthritics/month
  • Number of painful joints (NAD) > 3
  • Overall pain VAS (0_100) > 40 mm
  • Failure, intolerance or impossibility of repeated use of usual treatments: colchicine, NSAIDs, corticosteroids and anakinra
  • Use of an effective method of contraception in women of childbearing age until 3 months after the end of the study.
  • Informed consent

Exclusion Criteria:

  • Presence of anti-CPP antibodies > 50 IU/ml
  • Recurrent or chronic infections
  • History of severe infection (= requiring hospitalization)
  • Active infection
  • Vaccination with live or attenuated vaccine within 4 weeks prior to inclusion
  • History of intestinal ulceration or diverticulitis Untreated latent tuberculosis
  • History of viral hepatitis B ou C
  • Symptoms suggestive of demyelinating disease of the central nervous system
  • History of cancer, active cancer, or suspected cancer
  • Neutropenia < 2000 elements/mm3, thrombocytopenia < 100 000/mm3
  • Elevated transaminases > 3 x ULN
  • Known hypersensitivity to the active substance or one of the excipients;
  • Known severe immune deficiency
  • Patients not meeting classification criteria
  • Concomitant treatment with biological or targeted therapies, or immunosuppressive therapy (including methotrexate, leflunomide, azathioprine), systemic corticosteroids, anakinra, IL-6 inhibitors in subcutaneous injection, anti-TNF agents, and JAK. If these treatments are used before inclusion, a washout period corresponding to at least five times their respective mean terminal half-life must be respected.
  • inhibitors.
  • Previous treatment with tocilizumab
  • Concomitant treatment with methylprednisolone, dexamethasone, atorvastatin, calcium channel blockers, theophylline, warfarin, phenprocoumon, phenytoin, cyclosporine or benzodiazepines
  • Dyslipidemia, hypertension or poorly controlled cardiovascular disease
  • Scheduled surgery
  • Difficulty to understand French, illiteracy
  • Pregnant women, women in labor or nursing mothers
  • Persons deprived of their liberty, adults under legal protection or unable to express their consent
  • Persons not affiliated to a social security scheme or beneficiaries of such a scheme
  • Participation in another interventional study

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: Zufällig
  • Interventionsmodell: Parallele Zuordnung
  • Maskierung: Single

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Placebo-Komparator: Placebo
Sonstiges: Placebo

Saline placebo, IV infusion / month for 3 months
Experimental: Tocilizumab
Arzneimittel: Tocilizumab

Tocilizumab, 8 mg/kg/month, IV infusion for 3 months

Tocilizumab, an anti-IL-6R monoclonal antibody, was approved in January 2009 for the treatment of rheumatoid arthritis. Its indications have since been extended, particularly for the treatment of giant cell arteritis, juvenile chronic arthritis, and severe cytokine release syndrome induced by chimeric antigen receptor T-cell (CAR-T) therapy.

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Change in overall pain VAS
Zeitfenster: 6 months

Overall pain will be assessed, after 24 hours of discontinuation of analgesics, using a visual analogue scale (VAS) ranging from 0 (no pain) to 100 mm (worst pain ever experienced), at inclusion, before each infusion at months M1, M2, M3, then at M4 (primary outcome) and M6.
6 months

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Change in the number of swollen and tender joints
Zeitfenster: 6 months

Disease Activity Score (DAS28-CRP), number of swollen and painful joints, Patient assessment of overall disease activity by a visual analogue scale (VAS) ranging from 0 (no activity) to 100 mm (maximal activity). Those outcomes will be assessed at inclusion, before each infusion at months M1, M2, M3, then at M4 (primary outcome) and M6
6 months
Overall effect on pain
Zeitfenster: 6 months

Area under the curve (AUC) of the overall pain visual analogue scale (VAS) ranging from 0 (no pain) to 100 mm (worst pain ever experienced) based on assessments at baseline, before each infusion at months M1, M2, M3 and at M4 and M6 (end of the study). Overall pain VAS will be collected after a 24-hour washout of analgesics.
6 months
Response to treatment / relapse
Zeitfenster: 6 months

Response to treatment will be defined as an improvement ≥ 50% of initial pain visual analogue scale (VAS) ranging from 0 (no pain) to 100 mm (worst pain ever experienced) Complete response will be defined as an improvement ≥ 80% of initial pain VAS This outcome will be assessed from M2 to M6.

Relapse will be assessed in responders at 6 months, and the time from response to relapse will be determined.
6 months
Flares (ESR)
Zeitfenster: 6 months

Outcome Measures - Inflammatory Biomarkers

Erythrocyte Sedimentation Rate (ESR) Unit: millimeters (mm) Frequency: measured at each visit

No aggregation of this measure is planned to produce a composite value. If aggregation is considered (e.g., to generate an overall inflammation score), a validated statistical method will be specified.
6 months
Flares (CRP)
Zeitfenster: 6 months

Outcome Measures - Inflammatory Biomarkers

C-reactive Protein (CRP) Unit: milligrams per liter (mg/L) Frequency: measured at each visit

No aggregation of this measure is planned to produce a composite value. If aggregation is considered (e.g., to generate an overall inflammation score), a validated statistical method will be specified.
6 months
Flares (IL-6)
Zeitfenster: 6 months

Outcome Measures - Inflammatory Biomarkers

Interleukin-6 (IL-6) Unit: picograms per milliliter (pg/mL) Frequency: measured at each visit

No aggregation of this measure is planned to produce a composite value. If aggregation is considered (e.g., to generate an overall inflammation score), a validated statistical method will be specified.
6 months
Quality of life's Questionnaires (SF-36)
Zeitfenster: 6 months

Full Title: Short Form 36 Health Survey (SF-36) Scale Range: 0 to 100 per subscale Interpretation: Higher scores indicate better health status or quality of life Time Points: Baseline, prior to each infusion, and at Months 4 and 6 (M4 and M6) Unit: Score

This questionnaire will be analyzed and reported as a distinct outcome measure, in accordance with its specific scoring system.
6 months
Quality of life's Questionnaires (HAQ)
Zeitfenster: 6 months

Full Title: Health Assessment Questionnaire (HAQ) Scale Range: 0 to 3 Interpretation: Higher scores indicate worse functional ability (i.e., more disability) Time Points: Baseline, prior to each infusion, and at Months 4 and 6 (M4 and M6) Unit: Score

This questionnaire will be analyzed and reported as a distinct outcome measure, in accordance with its specific scoring system.
6 months
Quality of life's Questionnaires (EQ-5D-3L)
Zeitfenster: 6 months

Full Title: EuroQol Five Dimensions Three Levels (EQ-5D-3L) Scale Range: 0 to 100 Interpretation: Higher scores indicate better health-related quality of life Time Points: Baseline, prior to each infusion, and at Months 4 and 6 (M4 and M6) Unit: Index value

This questionnaire will be analyzed and reported as a distinct outcome measure, in accordance with its specific scoring system.
6 months
Patient Safety - Number of Participants with Adverse Events
Zeitfenster: 6 months

Outcome Measure - Number of Participants with Adverse Events

Description: Number of participants experiencing any of the following safety-related events at each visit:

  • Infusion reactions
  • Neutropenia
  • Thrombocytopenia
  • Hepatic cytolysis
  • Severe infections
  • Treatment-related adverse events
  • Abnormal changes in lipid profile

Unit of Measure: Count (participants) Time Points: Each visit Note: Each event type will be recorded and analyzed separately but reported under a unified outcome measure to reflect overall safety.
6 months
Patient Safety - Number of patients with abnormal laboratory tests results - Mean Neutrophil Count
Zeitfenster: 6 months

Description: Mean neutrophil count measured from blood samples collected at each visit.

Unit of Measure: normal: 2500-8000/μL; AE: <1500/μL
6 months
Patient Safety - Number of patients with abnormal laboratory tests results - Mean Platelet Count
Zeitfenster: 6 months

Description: Mean platelet count measured from blood samples collected at each visit.

Unit of Measure: normal: 150,000-400,000/μL; AE: <75,000/μL
6 months
Patient Safety - Number of patients with abnormal laboratory tests results - Mean Transaminase Levels
Zeitfenster: 6 months

Description: Mean levels of transaminases (e.g., ALT, AST) measured to assess hepatic cytolysis.

Unit of Measure: ALT/AST normal: <40 U/L; AE: >3×ULN
6 months
Patient Safety - Number of patients with abnormal laboratory tests results - Mean Lipid Profile Values
Zeitfenster: 6 months

Description: Mean values of lipid profile components (e.g., total cholesterol, LDL, HDL, triglycerides) measured at each visit.

Unit of Measure: normal: TC <200, LDL <130, HDL >45/55, TG <150 mg/dL
6 months

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

Assistance Publique - Hôpitaux de Paris

Mitarbeiter

Fresenius AG

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn (Geschätzt)

1. November 2026

Primärer Abschluss (Geschätzt)

1. November 2026

Studienabschluss (Geschätzt)

1. November 2029

Studienanmeldedaten

Zuerst eingereicht

14. August 2025

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

19. November 2025

Zuerst gepostet (Tatsächlich)

28. November 2025

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

10. November 2026

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

6. November 2026

Zuletzt verifiziert

1. November 2026

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

  • APHP220790

Plan für individuelle Teilnehmerdaten (IPD)

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NEIN

Arzneimittel- und Geräteinformationen, Studienunterlagen

Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt

Nein

Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt

Nein

Produkt, das in den USA hergestellt und aus den USA exportiert wird

Nein

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