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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Cryopyrin-Associated Periodic Syndromes
• Intervention / Treatment: Drug: Tranilast

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 Type: Interventional
• Enrollment (Anticipated): 71
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hongmei Song, Doctor; Phone Number: +86-10-69156271; Email: songhm1021@hotmail.com
• Study Contact Backup: Name: Linqing Zhong; Phone Number: +86-13011825185; Email: zhonglinqing_pumch@126.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Recruiting
      • Peking Union Medical College Hospital
      • Contact: Hongmei Song, Doctor; Phone Number: +86-10-69156271; Email: songhm1021@hotmail.com
      • Contact: Linqing Zhong; Phone Number: +86-13011825185; Email: zhonglinqing_pumch@126.com
      • Principal Investigator: Hongmei Song, Doctor
      • Sub-Investigator: Linqing Zhong

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All patients must meet the following diagnostic criteria of CAPS and have pathogenic mutation(s) in NLRP3 gene.

  1. Raised inflammatory markers (CRP/SAA) (mandatory criteria)

  2. ≥2 of 6 CAPS typical signs/symptoms:

     1. Urticaria-like rash;
     2. Cold/stress triggered episodes;
     3. Sensorineural hearing loss;
     4. Musculoskeletal symptoms (arthralgia/arthritis/myalgia);
     5. Chronic aseptic meningitis;
     6. Skeletal abnormalities (epiphyseal overgrowth/frontal bossing).

Exclusion Criteria:

• Patients will not be included if meets any of the following criteria:

  1. Being treated with IL-1 inhibitor, other biological agents and immunosuppressants
  2. Pregnant and lactating women
  3. Serious organ function failure, expected life time less than 6 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Investigators: Principal Investigator: Hongmei Song, Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 23, 2019
• Primary Completion (ANTICIPATED): April 1, 2024
• Study Completion (ANTICIPATED): October 1, 2024

Study Registration Dates

• First Submitted: April 14, 2019
• First Submitted That Met QC Criteria: April 19, 2019
• First Posted (ACTUAL): April 22, 2019

Study Record Updates

• Last Update Posted (ACTUAL): June 4, 2019
• Last Update Submitted That Met QC Criteria: June 1, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Safety; Efficacy; Tranilast; Cryopyrin-Associated Periodic Syndromes
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Disease; Genetic Diseases, Inborn; Hereditary Autoinflammatory Diseases; Skin Diseases, Genetic; Syndrome; Cryopyrin-Associated Periodic Syndromes; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Platelet Aggregation Inhibitors; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Anti-Allergic Agents; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Tranilast
• Other Study ID Numbers: ZS-1921

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No