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Tocilizumab w przewlekłej zapalnej chorobie CPPD (TociCCAre)

6 listopada 2026 zaktualizowane przez: Assistance Publique - Hôpitaux de Paris

Randomizowane, podwójnie ślepe, wieloośrodkowe badanie porównawcze tocilizumabu z placebo w przewlekłym zapalnym wielostawowym zapaleniu z depozycją kryształów pirofosforanu wapnia opornym na standardowe leczenie

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.

Przegląd badań

Status

Jeszcze nie rekrutacja

Warunki

Interwencja / Leczenie

Szczegółowy opis

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.

Typ studiów

Interwencyjne

Zapisy (Szacowany)

80

Faza

  • Faza 2

Kontakty i lokalizacje

Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.

Kontakt w sprawie studiów

Lokalizacje studiów

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

Kryteria uczestnictwa

Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.

Kryteria kwalifikacji

Wiek uprawniający do nauki

18 lat i starsze (Dorosły, Starszy dorosły)

Akceptuje zdrowych ochotników

Nie

Płeć kwalifikująca się do nauki

Wszystko

Opis

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

Plan studiów

Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.

Jak projektuje się badanie?

Szczegóły projektu

  • Główny cel: Leczenie
  • Przydział: Randomizowane
  • Model interwencyjny: Przydział równoległy
  • Maskowanie: Pojedynczy

Broń i interwencje

Grupa uczestników / Arm
Interwencja / Leczenie
Komparator placebo: Placebo
Inny: Placebo

Saline placebo, IV infusion / month for 3 months
Eksperymentalny: Tocilizumab
Lek: 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.

Co mierzy badanie?

Podstawowe miary wyniku

Miara wyniku
Opis środka
Ramy czasowe
Change in overall pain VAS
Ramy czasowe: 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

Miary wyników drugorzędnych

Miara wyniku
Opis środka
Ramy czasowe
Change in the number of swollen and tender joints
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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)
Ramy czasowe: 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)
Ramy czasowe: 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)
Ramy czasowe: 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)
Ramy czasowe: 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)
Ramy czasowe: 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)
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Sponsor

Assistance Publique - Hôpitaux de Paris

Współpracownicy

Fresenius AG

Daty zapisu na studia

Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.

Główne daty studiów

Rozpoczęcie studiów (Szacowany)

1 listopada 2026

Zakończenie podstawowe (Szacowany)

1 listopada 2026

Ukończenie studiów (Szacowany)

1 listopada 2029

Daty rejestracji na studia

Pierwszy przesłany

14 sierpnia 2025

Pierwszy przesłany, który spełnia kryteria kontroli jakości

19 listopada 2025

Pierwszy wysłany (Rzeczywisty)

28 listopada 2025

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Rzeczywisty)

10 listopada 2026

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

6 listopada 2026

Ostatnia weryfikacja

1 listopada 2026

Więcej informacji

Terminy związane z tym badaniem

Dodatkowe istotne warunki MeSH

Inne numery identyfikacyjne badania

  • APHP220790

Plan dla danych uczestnika indywidualnego (IPD)

Planujesz udostępniać dane poszczególnych uczestników (IPD)?

NIE

Informacje o lekach i urządzeniach, dokumenty badawcze

Bada produkt leczniczy regulowany przez amerykańską FDA

Nie

Bada produkt urządzenia regulowany przez amerykańską FDA

Nie

produkt wyprodukowany i wyeksportowany z USA

Nie

Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .

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