만성 염증성 CPPD 질환에서의 토실리주맙 (TociCCAre)
표준 치료에 반응하지 않는 만성 다발성 칼슘 피로인산 침착 질환에서 토실리주맙 대 위약의 무작위 배정, 이중 맹검, 다기관 임상시험
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.
연구 개요
상태
상태
정황
정황
개입 / 치료
개입 / 치료
상세 설명
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.
연구 유형
연구 유형
등록 (추정된)
등록
단계
단계
- 2 단계
연락처 및 위치
연구 연락처
연구 연락처
- 이름: Augustin Latourte, Associate Professor
- 전화번호: +33 1 49 95 62 90
- 이메일: augustin.latourte@aphp.fr
연구 장소
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Dijon, 프랑스, 21000
- CHU de Dijon
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연락하다:
- RAMON André, Dr
- 전화번호: 0380293745
- 이메일: andre.ramon@chu-dijon.fr
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Nantes, 프랑스, 44000
- CHU de Nantes
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연락하다:
- LE GOFF Benoit, Dr
- 전화번호: 0240083333
- 이메일: benoit.legoff@chu-nantes.fr
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Paris, 프랑스, 75020
- Hôpital Tenon
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연락하다:
- LETAVERNIER Emmanuel, Pr
- 전화번호: 0156016773
- 이메일: emmanuel.letavernier@aphp.fr
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Paris, 프랑스, 75020
- Hôpital de la Croix Saint-Simon
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연락하다:
- CHAZERAIN Pascal, Dr
- 전화번호: 0144641782
- 이메일: PChazerain@hopital-dcss.org
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Paris, 프랑스, 93370
- Groupe Hospitalier Intercommunal Le Raincy-Montfermeil
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연락하다:
- DELLAL Azzedine, Dr
- 전화번호: 0141708766
- 이메일: azeddine.dellal@ght-gpne.fr
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Paris, 프랑스, 94270
- Hôpital Le Kremlin Bicêtre
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Paris, 프랑스, 75018
- Hôpital Bichat Claude-Bernard
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연락하다:
- OTTAVIANI Sébastien
- 전화번호: 0140258739
- 이메일: sebastien.ottaviani@aphp.fr
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Pontoise, 프랑스, 95300
- Hôpital NOVO
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연락하다:
- Omar AL TABAA, Docteur
- 전화번호: 01 30 75 40 40
- 이메일: omar.altabaa@ght-novo.fr
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Rennes, 프랑스, 35200
- CHU de Rennes
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연락하다:
- CHOTARD Emilie, Dr
- 전화번호: 0299267140
- 이메일: Emilie.CHOTARD@chu-rennes.fr
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Saint-Etienne, 프랑스, 42100
- CHU de Saint-Étienne
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연락하다:
- MAROTTE Hubert, Pr
- 전화번호: 0477127643
- 이메일: hubert.marotte@chu-st-etienne.fr
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Lille
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Lomme, Lille, 프랑스, 59462
- Groupe Hospitalier de l'Institut Catholique de Lille
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연락하다:
- PASCART Tristan, Dr
- 전화번호: 0320225059
- 이메일: pascart.tristan@ghicl.net
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Paris
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Corbeil-Essonnes, Paris, 프랑스, 91100
- Centre Hospitalier Sud-Francilien
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연락하다:
- HILLIQUIN Pascal, Dr
- 전화번호: 0161693128
- 이메일: pascal.hilliquin@chsf.fr
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Paris Paris
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Paris, Paris Paris, 프랑스, 75010
- Lariboisière hospital
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참여기준
자격 기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
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
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 하나의
팔의 수
무기와 개입
참가자 그룹 / 팔참가자 그룹 / 팔 |
개입 / 치료개입 / 치료 |
|---|---|
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위약 비교기: 위약
|
Saline placebo, IV infusion / month for 3 months |
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실험적: 토실리주맙
|
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. |
연구는 무엇을 측정합니까?
주요 결과 측정
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Change in overall pain VAS
기간: 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
|
2차 결과 측정
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Change in the number of swollen and tender joints
기간: 6 months
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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
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Overall effect on pain
기간: 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
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Response to treatment / relapse
기간: 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
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Flares (ESR)
기간: 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)
기간: 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
|
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Flares (IL-6)
기간: 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)
기간: 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)
기간: 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)
기간: 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
기간: 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:
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
|
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Patient Safety - Number of patients with abnormal laboratory tests results - Mean Neutrophil Count
기간: 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
기간: 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
기간: 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
기간: 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
|
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연구 기록 날짜
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연구 시작
기본 완료 (추정된)
기본 완료
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연구 기록 업데이트
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기타 연구 ID 번호
기타 연구 ID 번호
- APHP220790
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