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

Primary Purpose

Cryopyrin-Associated Periodic Syndromes

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Tranilast
Sponsored by
Peking Union Medical College Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cryopyrin-Associated Periodic Syndromes focused on measuring Cryopyrin-Associated Periodic Syndromes, Tranilast, Efficacy, Safety

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Peking Union Medical College HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Tranilast

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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).
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).
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.
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.
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.
Number of participants with adverse effect
Treatment-related adverse effect, including abnormal liver function, hematuria and decreased white blood cells

Full Information

First Posted
April 14, 2019
Last Updated
June 1, 2019
Sponsor
Peking Union Medical College Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03923140
Brief Title
A Clinical Study of Tranilast in the Treatment of Cryopyrin-Associated Periodic Syndrome (CAPS)
Official Title
Efficacy and Safety of Tranilast in Patients With Cryopyrin-Associated Periodic Syndrome (CAPS): A Single-Arm Prospective Cohort Study
Study Type
Interventional

2. Study Status

Record Verification Date
June 2019
Overall Recruitment Status
Recruiting
Study Start Date
May 23, 2019 (Actual)
Primary Completion Date
April 2024 (Anticipated)
Study Completion Date
October 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Peking Union Medical College Hospital

4. Oversight

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

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cryopyrin-Associated Periodic Syndromes
Keywords
Cryopyrin-Associated Periodic Syndromes, Tranilast, Efficacy, Safety

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
a single-arm prospective cohort study
Masking
None (Open Label)
Allocation
N/A
Enrollment
71 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Tranilast
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Tranilast
Other Intervention Name(s)
Rizaben
Intervention Description
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
Primary Outcome Measure Information:
Title
Changes in Auto-Inflammatory Diseases Activity Index score after 6-month treatment over baseline
Description
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.
Time Frame
The previous 1 month before treatment and the 6th month after treatment
Secondary Outcome Measure Information:
Title
Changes in Auto-Inflammatory Diseases Activity Index score at the 1st and 3rd month over baseline
Description
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.
Time Frame
The previous 1 month before treatment and the 1st and 3rd month after treatment
Title
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
Description
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.
Time Frame
Baseline and at 1, 3 and 6 months after treatment
Title
Changes in physician global assessment of disease activity on a 0-10 visual analog scale (VAS) at 1, 3 and 6 months over baseline
Description
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).
Time Frame
Baseline and 1, 3 and 6 months after treatment
Title
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
Description
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).
Time Frame
Baseline and 1, 3 and 6 months after treatment
Title
Changes in CSF white blood cell count for CINCA patients
Description
For CINCA patients, Lumbar punctures (LPs) were performed at baseline and 6 months after treatment.
Time Frame
Baseline and 6 months after treatment.
Title
Changes in MRI of the brain and inner ear for CINCA patients
Description
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.
Time Frame
Baseline and 6 months after treatment.
Title
Changes in audiology data for CINCA patients
Description
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.
Time Frame
Baseline and 6 months after treatment.
Title
Number of participants with adverse effect
Description
Treatment-related adverse effect, including abnormal liver function, hematuria and decreased white blood cells
Time Frame
Up to 6 months

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hongmei Song, Doctor
Phone
+86-10-69156271
Email
songhm1021@hotmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Linqing Zhong
Phone
+86-13011825185
Email
zhonglinqing_pumch@126.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hongmei Song
Organizational Affiliation
Peking Union Medical College Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Peking Union Medical College Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100730
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hongmei Song, Doctor
Phone
+86-10-69156271
Email
songhm1021@hotmail.com
First Name & Middle Initial & Last Name & Degree
Linqing Zhong
Phone
+86-13011825185
Email
zhonglinqing_pumch@126.com
First Name & Middle Initial & Last Name & Degree
Hongmei Song, Doctor
First Name & Middle Initial & Last Name & Degree
Linqing Zhong

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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