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Tocilizumab ved Kronisk Inflammatorisk CPPD-sygdom (TociCCAre)

6. november 2026 opdateret af: Assistance Publique - Hôpitaux de Paris

Randomiseret, dobbeltblind, multicentrisk undersøgelse af Tocilizumab versus placebo ved kronisk polyartikulær betændelse i forbindelse med calciumpyrofosfat-aflejringssygdom refraktær til standardbehandlinger

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.

Studieoversigt

Status

Ikke rekrutterer endnu

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Anslået)

80

Fase

  • Fase 2

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiekontakt

Studiesteder

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

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Enkelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Placebo komparator: Placebo
Andet: Placebo

Saline placebo, IV infusion / month for 3 months
Eksperimentel: Tocilizumab
Medicin: 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.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Change in overall pain VAS
Tidsramme: 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

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Change in the number of swollen and tender joints
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Assistance Publique - Hôpitaux de Paris

Samarbejdspartnere

Fresenius AG

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Anslået)

1. november 2026

Primær færdiggørelse (Anslået)

1. november 2026

Studieafslutning (Anslået)

1. november 2029

Datoer for studieregistrering

Først indsendt

14. august 2025

Først indsendt, der opfyldte QC-kriterier

19. november 2025

Først opslået (Faktiske)

28. november 2025

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

10. november 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

6. november 2026

Sidst verificeret

1. november 2026

Mere information

Begreber relateret til denne undersøgelse

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • APHP220790

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