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

Sponsor

Peking Union Medical College Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT03923140

Collaborator

(none)

Enrollment

Location

Arm

64.3

Anticipated Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Cryopyrin-Associated Periodic Syndromes	Drug: Tranilast	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

71 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

a single-arm prospective cohort studya single-arm prospective cohort study

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

May 23, 2019

Anticipated Primary Completion Date :

Apr 1, 2024

Anticipated Study Completion Date :

Oct 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tranilast 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 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 Other Names: Rizaben

Arm

Intervention/Treatment

Experimental: Tranilast

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

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

Other Names:

Rizaben

Outcome Measures

Primary Outcome Measures

Changes in Auto-Inflammatory Diseases Activity Index score after 6-month treatment over baseline [The previous 1 month before treatment and the 6th month after treatment]
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.

Secondary Outcome Measures

Changes in Auto-Inflammatory Diseases Activity Index score at the 1st and 3rd month over baseline [The previous 1 month before treatment and the 1st and 3rd month after treatment]
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.
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 [Baseline and at 1, 3 and 6 months after treatment]
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.
Changes in physician global assessment of disease activity on a 0-10 visual analog scale (VAS) at 1, 3 and 6 months over baseline [Baseline and 1, 3 and 6 months after treatment]
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).
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 [Baseline and 1, 3 and 6 months after treatment]
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).
Changes in CSF white blood cell count for CINCA patients [Baseline and 6 months after treatment.]
For CINCA patients, Lumbar punctures (LPs) were performed at baseline and 6 months after treatment.
Changes in MRI of the brain and inner ear for CINCA patients [Baseline and 6 months after treatment.]
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.
Changes in audiology data for CINCA patients [Baseline and 6 months after treatment.]
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.
Number of participants with adverse effect [Up to 6 months]
Treatment-related adverse effect, including abnormal liver function, hematuria and decreased white blood cells

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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