Back to resultsEvaluation of TNF-alpha Antagonists (Infliximab) Withdrawal in Sarcoidosis (TAWIS)
Primary Purpose
Sarcoidosis
Status
Recruiting
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
STOP arm
Sponsored by
About this trial
This is an interventional treatment trial for Sarcoidosis
Eligibility Criteria
Inclusion Criteria: Age superior or equal to 18 years Clinical and radiological presentation consistent with sarcoidosis Presence of non-caseating granulomas in at least one organ Exclusion or other causes of granulomas Infliximab treatment for at least 6 months Steroid dosage < or equal to 10 mg/day for at least 6 months No activity of the disease (ePOST score 0) for at least 6 months Normal ACE (angiotensin converting enzyme) and serum calcemia level Signed informed consent Affiliated to the National French social security system As infliximab is the most used TNF-alpha antagonists, we decided to include only patients treated with infliximab to increase the homogeneity. Exclusion Criteria: Pregnancy or breast-feeding Positive IGRA (Interferon Gamma Release Assays) test without previous antituberculous antibiotherapy Active infection Patients with moderate to severe heart failure (NYHA class III/ IV) Severe liver function disorders Alcoholism Severe kidney function disorders Pre-existing blood dyscrasias History of cancer in the 5 years before enrolment (except for cutaneous non melanoma cancers) Concurrent vaccination with live vaccines during therapy Inability to understand information about protocol Adult subject under legal protection or unable ton consent Absence of effective contraceptive method for men and women for duration of the study and 6 months after the end of participation Concomitant participation to another biomedical research (only Category 1 trial according to the french law)
Sites / Locations
- Hôpital de la Pitié-SalpêtrièreRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
No Intervention
Other
Arm Label
REMAIN arm
STOP arm
Arm Description
Infliximab 3 to 5 mg/kg every 4-8 weeks, methotrexate 7.5-10 mg/week (or azathioprine 1 mg/Kg/day), steroids < or = 10 mg/day
Methotrexate 0.3 mg/kg/week (or azathioprine 2 mg/kg/day (or 1 mg/kg/day if intermediary metabolism TMPT) (the dose of methotrexate will not exceed 25mg/kg/week wathever the weight of the patient), steroids < or = 10 mg/d
Outcomes
Primary Outcome Measures
To compare 2 strategies of remission maintenance in patients who are in remission after infliximab administration
Percentage of patients with major relapse (reappearance or worsening of the disease with a ePOST score >0 and involvement of at least one major organ, a life-threatening situation, or both or relapse non responsive to mild treatment intensification) between enrolment and month 12.
Major organs are nervous system, heart, kidneys, muscles and lungs. Mild treatment intensification is defined by increasing the dosage of steroids at more than 20 milligrams/day.
The primary criterion will be assessed at each visit, in case of relapse and at the end of follow-up (M12).
Secondary Outcome Measures
To compare the percentage of patients with minor relapses in the 2 groups
Percentage of patients with minor relapse (reappearance or worsening of the disease with a ePOST score > 0 not corresponding to the definition of major relapse) at months 12.
To compare the rates of adverse events
All adverse events occurred between enrolment and Month 12, will be noted with special attention to infection, haematological toxicities and cancers.
To determine which are the predictors of relapses
Percentage of patients with a previous heart involvement at inclusion
To determine which are the predictives of relapses
Percentage of patients with nervous system involvement at inclusion
To determine which are the relapsing predictors
Percentage of patients with hypermetabolism elsewhere consistent with sarcoidosis localization in positron emission tomography scan (PET scan) at inclusion
To determine which are the prediction of relapses
Serum ACE (angiotensin converting enzyme) level at inclusion
To compare results of Short Form (36) Health Survey in the 2 groups
Quality of life will be assessed by SF-36 (Short Form (36) Health Survey) at inclusion, Month 6 and Month 12 (score from 0 to 100, the higher score is the better).
Compare results of Nottingham scale of each groups
Quality of life will be assessed by Nottingham scale at inclusion, Month 6 and Month 12 (score from 0 to 38, the higher score is the worse) .
To compare results of Fatigue Assessment Scale in the 2 groups
Quality of life will be assessed by Fatigue Assessment Scale (FAS, Patel 2000) at inclusion, Month 6 and Month 12 (score from 10 to 50, the higher score is the worse) .
Full Information
NCT ID
NCT05689879
First Posted
May 2, 2022
Last Updated
April 13, 2023
Sponsor
Assistance Publique - Hôpitaux de Paris
1. Study Identification
Unique Protocol Identification Number
NCT05689879
Brief Title
Evaluation of TNF-alpha Antagonists (Infliximab) Withdrawal in Sarcoidosis
Acronym
TAWIS
Official Title
Evaluation of TNF-alpha Antagonists (Infliximab) Withdrawal in Sarcoidosis : a Prospective, Randomized, Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 23, 2023 (Actual)
Primary Completion Date
March 2026 (Anticipated)
Study Completion Date
March 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
In severe refractory sarcoidosis not responding to conventional immunosuppressive treatment, the third-line tumor necrosis factor (TNF)-alpha inhibitor infliximab is an alternative. Treatment duration is not known, although it has been suggested that relapse rates after withdrawal could be high. We hypothesize that a prolonged course of TNF-alpha would be better for maintaining remission in sarcoidosis.
The population consists of histologically-proven adults sarcoidosis patients who were treated with infliximab and are in remission for at least 6 months with less than or equal to 10 milligrams of steroids (prednisone).
The present study is a phase 3, prospective, randomized, parallel groups, comparative, open-labelled 2 arms study superiority trial comparing a STOP to a REMAIN strategy. Patients will be randomized in the 2 groups in a 1:1 ratio.
Detailed Description
The screening visit takes place between 60 days and until the baseline visit. The investigator will first check that the patient meets the inclusion criteria and does not present exclusion criteria. Before enrolment and randomization, all patients will receive comprehensive information and provide written consent.
Visit schedule:
Baseline visit
Follow-up Visits In the REMAIN arm: visits will be performed each 4-8 weeks depending on the infliximab interval. In the STOP arm, visits will be performed every 8 weeks, and in case of relapse (until M12+/- 2 weeks).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sarcoidosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Infliximab stop Methotrexate (without exceed 25mg/kg/week) or azathioprine
Masking
None (Open Label)
Masking Description
No masking
Allocation
Randomized
Enrollment
90 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
REMAIN arm
Arm Type
No Intervention
Arm Description
Infliximab 3 to 5 mg/kg every 4-8 weeks, methotrexate 7.5-10 mg/week (or azathioprine 1 mg/Kg/day), steroids < or = 10 mg/day
Arm Title
STOP arm
Arm Type
Other
Arm Description
Methotrexate 0.3 mg/kg/week (or azathioprine 2 mg/kg/day (or 1 mg/kg/day if intermediary metabolism TMPT) (the dose of methotrexate will not exceed 25mg/kg/week wathever the weight of the patient), steroids < or = 10 mg/d
Intervention Type
Drug
Intervention Name(s)
STOP arm
Other Intervention Name(s)
TNF-alpha antagonists withdrawal
Intervention Description
TNF-alpha antagonists withdrawal
Primary Outcome Measure Information:
Title
To compare 2 strategies of remission maintenance in patients who are in remission after infliximab administration
Description
Percentage of patients with major relapse (reappearance or worsening of the disease with a ePOST score >0 and involvement of at least one major organ, a life-threatening situation, or both or relapse non responsive to mild treatment intensification) between enrolment and month 12.
Major organs are nervous system, heart, kidneys, muscles and lungs. Mild treatment intensification is defined by increasing the dosage of steroids at more than 20 milligrams/day.
The primary criterion will be assessed at each visit, in case of relapse and at the end of follow-up (M12).
Time Frame
12 months
Secondary Outcome Measure Information:
Title
To compare the percentage of patients with minor relapses in the 2 groups
Description
Percentage of patients with minor relapse (reappearance or worsening of the disease with a ePOST score > 0 not corresponding to the definition of major relapse) at months 12.
Time Frame
12 months
Title
To compare the rates of adverse events
Description
All adverse events occurred between enrolment and Month 12, will be noted with special attention to infection, haematological toxicities and cancers.
Time Frame
12 months
Title
To determine which are the predictors of relapses
Description
Percentage of patients with a previous heart involvement at inclusion
Time Frame
12 months
Title
To determine which are the predictives of relapses
Description
Percentage of patients with nervous system involvement at inclusion
Time Frame
12 months
Title
To determine which are the relapsing predictors
Description
Percentage of patients with hypermetabolism elsewhere consistent with sarcoidosis localization in positron emission tomography scan (PET scan) at inclusion
Time Frame
12 months
Title
To determine which are the prediction of relapses
Description
Serum ACE (angiotensin converting enzyme) level at inclusion
Time Frame
12 months
Title
To compare results of Short Form (36) Health Survey in the 2 groups
Description
Quality of life will be assessed by SF-36 (Short Form (36) Health Survey) at inclusion, Month 6 and Month 12 (score from 0 to 100, the higher score is the better).
Time Frame
12 mois
Title
Compare results of Nottingham scale of each groups
Description
Quality of life will be assessed by Nottingham scale at inclusion, Month 6 and Month 12 (score from 0 to 38, the higher score is the worse) .
Time Frame
12 mois
Title
To compare results of Fatigue Assessment Scale in the 2 groups
Description
Quality of life will be assessed by Fatigue Assessment Scale (FAS, Patel 2000) at inclusion, Month 6 and Month 12 (score from 10 to 50, the higher score is the worse) .
Time Frame
12 mois
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age superior or equal to 18 years
Clinical and radiological presentation consistent with sarcoidosis
Presence of non-caseating granulomas in at least one organ
Exclusion or other causes of granulomas
Infliximab treatment for at least 6 months
Steroid dosage < or equal to 10 mg/day for at least 6 months
No activity of the disease (ePOST score 0) for at least 6 months
Normal ACE (angiotensin converting enzyme) and serum calcemia level
Signed informed consent
Affiliated to the National French social security system
As infliximab is the most used TNF-alpha antagonists, we decided to include only patients treated with infliximab to increase the homogeneity.
Exclusion Criteria:
Pregnancy or breast-feeding
Positive IGRA (Interferon Gamma Release Assays) test without previous antituberculous antibiotherapy
Active infection
Patients with moderate to severe heart failure (NYHA class III/ IV)
Severe liver function disorders
Alcoholism
Severe kidney function disorders
Pre-existing blood dyscrasias
History of cancer in the 5 years before enrolment (except for cutaneous non melanoma cancers)
Concurrent vaccination with live vaccines during therapy
Inability to understand information about protocol
Adult subject under legal protection or unable ton consent
Absence of effective contraceptive method for men and women for duration of the study and 6 months after the end of participation
Concomitant participation to another biomedical research (only Category 1 trial according to the french law)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Fleur COHEN AUBART, PHD
Phone
+ 33 1 42 17 82 42
Email
fleur.cohen@aphp.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fleur COHEN AUBART, PHD
Organizational Affiliation
Internal Medicine Department 2 - Hôpital Pitié-Salpêtrière
Official's Role
Study Director
Facility Information:
Facility Name
Hôpital de la Pitié-Salpêtrière
City
Paris
ZIP/Postal Code
75013
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fleur Dr COHEN-AUBART
Phone
142178242
Ext
+33
Email
fleur.cohen@aphp.fr
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Evaluation of TNF-alpha Antagonists (Infliximab) Withdrawal in Sarcoidosis
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