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

NCT05689879 | Active Not Recruiting Phase 3

• 1 other identifier: P160922
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Sarcoidosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• To compare the percentage of patients with minor relapses in the 2 groups

  12 months

• To compare the rates of adverse events

  12 months

• To determine which are the predictors of relapses

  12 months

• To determine which are the predictives of relapses

  12 months

• To determine which are the relapsing predictors

  12 months

Study Arms (2)

REMAIN arm

NO INTERVENTION

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

STOP arm

OTHER

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

Drug: STOP arm

Interventions

STOP arm DRUG

TNF-alpha antagonists withdrawal

Also known as: TNF-alpha antagonists withdrawal

STOP arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age superior or equal to 18 years
• Clinical and radiological presentation consistent with sarcoidosis
• Presence of non-caseating granulomas in at least one organ
• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hôpital de la Pitié-Salpêtrière

Paris, 75013, France

Location

MeSH Terms

Conditions

Sarcoidosis

Condition Hierarchy (Ancestors)

Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Delayed; Hypersensitivity; Immune System Diseases

Study Officials

• Fleur COHEN AUBART, PHD

  Internal Medicine Department 2 - Hôpital Pitié-Salpêtrière

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: No masking
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Infliximab stop Methotrexate (without exceed 25mg/kg/week) or azathioprine

Study Record Dates

• First Submitted: May 2, 2022
• First Posted: January 19, 2023
• Study Start: March 23, 2023
• Primary Completion (Estimated): January 12, 2027
• Study Completion (Estimated): January 12, 2027
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)