Evaluation of TNF-alpha Antagonists (Infliximab) Withdrawal in Sarcoidosis (TAWIS)

April 13, 2023 updated by: Assistance Publique - Hôpitaux de Paris

Evaluation of TNF-alpha Antagonists (Infliximab) Withdrawal in Sarcoidosis : a Prospective, Randomized, Controlled Trial

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Anticipated)

90

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Paris, France, 75013
        • Recruiting
        • Hôpital de la Pitié-Salpétrière
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: REMAIN arm
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
Other: STOP arm
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
TNF-alpha antagonists withdrawal
Other Names:
  • TNF-alpha antagonists withdrawal

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To compare 2 strategies of remission maintenance in patients who are in remission after infliximab administration
Time Frame: 12 months

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).

12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To compare the percentage of patients with minor relapses in the 2 groups
Time Frame: 12 months
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.
12 months
To compare the rates of adverse events
Time Frame: 12 months
All adverse events occurred between enrolment and Month 12, will be noted with special attention to infection, haematological toxicities and cancers.
12 months
To determine which are the predictors of relapses
Time Frame: 12 months
Percentage of patients with a previous heart involvement at inclusion
12 months
To determine which are the predictives of relapses
Time Frame: 12 months
Percentage of patients with nervous system involvement at inclusion
12 months
To determine which are the relapsing predictors
Time Frame: 12 months
Percentage of patients with hypermetabolism elsewhere consistent with sarcoidosis localization in positron emission tomography scan (PET scan) at inclusion
12 months
To determine which are the prediction of relapses
Time Frame: 12 months
Serum ACE (angiotensin converting enzyme) level at inclusion
12 months
To compare results of Short Form (36) Health Survey in the 2 groups
Time Frame: 12 mois
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).
12 mois
Compare results of Nottingham scale of each groups
Time Frame: 12 mois
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) .
12 mois
To compare results of Fatigue Assessment Scale in the 2 groups
Time Frame: 12 mois
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) .
12 mois

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 23, 2023

Primary Completion (Anticipated)

March 1, 2026

Study Completion (Anticipated)

March 1, 2027

Study Registration Dates

First Submitted

May 2, 2022

First Submitted That Met QC Criteria

January 16, 2023

First Posted (Actual)

January 19, 2023

Study Record Updates

Last Update Posted (Actual)

April 18, 2023

Last Update Submitted That Met QC Criteria

April 13, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Other Study ID Numbers

  • P160922

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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