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

Sarcoidosis Clinical Trial

— TAWIS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05689879
• Other study ID #: P160922
• Status: Recruiting
• Phase: Phase 3
• Start date: March 23, 2023
• Est. completion date: March 2027

Study information

• Verified date: April 2023
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Fleur COHEN AUBART, PHD
• Phone: + 33 1 42 17 82 42
• Email: fleur.cohen[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: March 2027
• Est. primary completion date: March 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Sarcoidosis

Intervention

Drug:
• STOP arm
TNF-alpha antagonists withdrawal

Locations

Country	Name	City	State
France	Hôpital de la Pitié-Salpêtrière	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	12 months
Secondary	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.	12 months
Secondary	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.	12 months
Secondary	To determine which are the predictors of relapses	Percentage of patients with a previous heart involvement at inclusion	12 months
Secondary	To determine which are the predictives of relapses	Percentage of patients with nervous system involvement at inclusion	12 months
Secondary	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	12 months
Secondary	To determine which are the prediction of relapses	Serum ACE (angiotensin converting enzyme) level at inclusion	12 months
Secondary	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).	12 mois
Secondary	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) .	12 mois
Secondary	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) .	12 mois