A Clinical Study of Tranilast in the Treatment of Cryopyrin-Associated Periodic Syndrome (CAPS)

Study Overview
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Brief Summary
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This is a prospective cohort study to observe the efficacy and safety of tranilast in CAPS patients. The investigators would analyze the changes in Auto-Inflammatory Diseases Activity Index (AIDAI) before and after treatment as well as changes in inflammatory markers, patients' and physician's global assessment of disease activity to determine the efficacy and safety of tranilast.

Detailed Description
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Seventy-one patients with CAPS will be recruited. After signing the informed consent, they will be administrated with tranilast (For juvenile patients, 5mg/kg.d with a maximum dose of 0.3g per day; For adult patients, the dose is 0.1g each time, three times a day). These patients will be followed up for 6 months. AIDAI is recorded by patients' or their parents one month before the start of treatment, and at the 1st, 3rd and 6th month after the treatment. Inflammatory markers, and patients' and physician's global assessment of disease activity will be assessed during the 1st, 3rd and 6th month follow-up. Side effects will be monitored and recorded as well. Experimental data before and after the administration of tranilast will be analyzed and be statistically processed, to figure out whether tranilast is effective and safe for CAPS patients.

Official Title
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Efficacy and Safety of Tranilast in Patients With Cryopyrin-Associated Periodic Syndrome (CAPS): A Single-Arm Prospective Cohort Study

Conditions
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Cryopyrin-Associated Periodic Syndromes

Intervention / Treatment
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* Drug: Tranilast


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients must meet the following diagnostic criteria of CAPS and have pathogenic mutation(s) in NLRP3 gene. Raised inflammatory markers (CRP/SAA) (mandatory criteria) ≥2 of 6 CAPS typical signs/symptoms: Urticaria-like rash; Cold/stress triggered episodes; Sensorineural hearing loss; Musculoskeletal symptoms (arthralgia/arthritis/myalgia); Chronic aseptic meningitis; Skeletal abnormalities (epiphyseal overgrowth/frontal bossing). Exclusion Criteria: Patients will not be included if meets any of the following criteria: Being treated with IL-1 inhibitor, other biological agents and immunosuppressants Pregnant and lactating women Serious organ function failure, expected life time less than 6 months
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: a single-arm prospective cohort study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tranilast<br>5mg/kg.d for juvenile patients with a maximum dose of 0.3g per day; 0.1g each time, three times a day for adults patients | Drug: Tranilast<br>* 5mg/kg.d for juvenile patients with a maximum dose of 0.3g per day; 0.1g each time, three times a day for adults patients<br>* Other names: Rizaben;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Auto-Inflammatory Diseases Activity Index score after 6-month treatment over baseline | Patients or their parents completed a 1-month (31 days) prospective diary with 12 yes/no items( Fever ≥38°C, Overall symptoms, Abdominal pain, Nausea/vomiting, Diarrhoea, Headaches, Chest pain, Painful nodes, Arthralgia or myalgia, Swelling of the joints, Eye manifestations, Skin rash) at the previous 1 month before treatment, and the 6th month after treatment . Each item of this diary was dichotomised as no (0)=absence of symptom or yes (1)=presence of symptom. The calculation of the Auto-Inflammatory Diseases Activity Index score is straightforward, consisting of the sum of all 12 items (0-372 in a month of 31 days). Higher values represent higher disease activity. | The previous 1 month before treatment and the 6th month after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Auto-Inflammatory Diseases Activity Index score at the 1st and 3rd month over baseline | Patients or their parents completed a 1-month (31 days) prospective diary with 12 yes/no items( Fever ≥38°C, Overall symptoms, Abdominal pain, Nausea/vomiting, Diarrhoea, Headaches, Chest pain, Painful nodes, Arthralgia or myalgia, Swelling of the joints, Eye manifestations, Skin rash) at the previous 1 month before treatment, and the 1st and 3rd month after treatment . Each item of this diary was dichotomised as no (0)=absence of symptom or yes (1)=presence of symptom. The calculation of the Auto-Inflammatory Diseases Activity Index score is straightforward, consisting of the sum of all 12 items (0-372 in a month of 31 days). Higher values represent higher disease activity. | The previous 1 month before treatment and the 1st and 3rd month after treatment | 
| Changes in inflammatory markers, including C-reactin protein, erythrocyte sedimentation rate, serum amyloid protein, interleukin-1β and interleukin-18， at 1, 3 and 6 months over baseline | C-reactin protein, erythrocyte sedimentation rate, serum amyloid protein, interleukin-1β and interleukin-18 are measured at baseline，1, 3 and 6 months after treatment. | Baseline and at 1, 3 and 6 months after treatment | 
| Changes in physician global assessment of disease activity on a 0-10 visual analog scale (VAS) at 1, 3 and 6 months over baseline | Visual analogue scale (VAS) for overall disease activity were completed by the physician at each visit (Baseline and 1, 3 and 6 months after treatment). | Baseline and 1, 3 and 6 months after treatment | 
| Changes in parent/patient global assessment of well-being on a 0-10 visual analogue score (VAS) at 1, 3 and 6 months over baseline | Visual analogue scale (VAS) for overall disease activity were completed by the parent/patient at each visit (Baseline and 1, 3 and 6 months after treatment). | Baseline and 1, 3 and 6 months after treatment | 
| Changes in CSF white blood cell count for CINCA patients | For CINCA patients, Lumbar punctures (LPs) were performed at baseline and 6 months after treatment. | Baseline and 6 months after treatment. | 
| Changes in MRI of the brain and inner ear for CINCA patients | For CINCA patients, MRIs with gadoliniumenhanced fluid-attenuated inversion recovery (FLAIR) sequences of the brain and inner ear were performed and scored at baseline and 6 months after treatment. | Baseline and 6 months after treatment. | 
| Changes in audiology data for CINCA patients | For CINCA patients, Hearing assessment included audiological evaluations. Outcomes in each ear were categorised as 'stable' or 'worsened', according to a modification of the American Speech and Hearing Association (ASHA) criteria, comparing the results at 6 months after treatment over baseline. | Baseline and 6 months after treatment. | 
| Number of participants with adverse effect | Treatment-related adverse effect, including abnormal liver function, hematuria and decreased white blood cells | Up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cryopyrin-Associated Periodic Syndromes, Tranilast, Efficacy, Safety