Efficacy of Remission-induction Regimen With Infliximab for Severe Extrathoracic Sarcoidosis (EFIRTES) (EFIRTES)

February 5, 2024 updated by: Assistance Publique - Hôpitaux de Paris

Efficacy of Remission-induction Regimen With Infliximab for Severe Extrathoracic Sarcoidosis (EFIRTES STUDY)

The present study was designed to assess the efficacy of infliximab in a 2-period study :

  • An initial period with comparison of infliximab versus placebo and allowing the determination of the primary criteria
  • Then an extension period in which the 2 arms will receive infliximab (in the placebo group : 5 perfusions and in the experimental group 3 supplemental perfusions). Finally, the 2 groups will receive 5 injections of infliximab There is little evidence in the literature of when and how infliximab should be administered in sarcoidosis. We hypothesized, from our personal experience in 30 cases (18 of which were reported in a retrospective trial (14), that infliximab would have a very quick activity. So it appeared reasonable to evaluate the primary criterion at 6 weeks after initiation of the treatment.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Sarcoidosis is a multisystemic granulomatous disease of unknown cause . Sarcoidosis is chronic and progressive in 25 % of the patients. Although mediastinal lymph nodes and lung are the most frequently sites affected, extrathoracic localizations may occur. In particular, cardiac or neurological localizations are frequently associated with a chronic disease, with subsequent morbidity and mortality. Such patients require long term therapy to avoid organ dysfunction which may occur with fibrosis.

If cyclophosphamide remains the "historical" treatment to treat resistant sarcoidosis, it can present serious adverse effects such as infections and gonadic toxicity which may be a problem in young people. As infliximab has demonstrated a real efficacy in resistant sarcoidosis, we challenged that it could be a valuable option for resistant extra-thoracic sarcoidosis.

The population studied will be the patients with clinical and radiological presentation concordant with sarcoidosis

This study is a phase 3, randomized, controlled, parallel group trial, designed to assess the efficacy of infliximab in a 2-period study :

In the first part, patients will be randomly assigned in a 1:1 ratio to receive either infliximab or placebo. Both patients and investigators will be blind regarding study treatment. Concomitantly, patients will be treated with usual care (i.e. steroids at the dose of 0.5 mg/kg/d with a program of tapering dose).

In the second open-labelled part, all the patients will receive infliximab treatment, steroids tapering regimen and low-dose methotrexate left to the investigator choice or, in case of contra-indication, azathioprine.

Finally, the 2 groups will receive 5 injections of infliximab

Infliximab will be used at a dose of 5 mg/kg at D1,D15 then every 4 weeks because in our experience, extrathoracic severe localization require such dosage and may be resistant to the low dosage (3 mg/kg). This dosage is also the dose usually recommended for extra-thoracic localizations.

Disease activity and ePOST score will be evaluated at the inclusion, W6 and after 5 injections (2 weeks after W20 for placebo group or W14 for experimental group). Severity assessment score (ePOST score) will be assessed by the physician in charge of the patient. This score reflects the sarcoidosis activity in 17 organs and has been validated in previous studies.

Remission at week 6 will be defined as: Percentage of patients who have a severity assessment score (ePOST score) inferior to 1 in all organs and absence of hypercalcemia at W6, whatever the corticosteroid dosage received.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
31

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • France
      • Bobigny, France, 93000
        • Hopital Avicenne - service de pnaumologie
      • Créteil, France, 94000
        • Hopital Henri Mondor- service de Médecine Interne
      • Lille, France, 59000
        • Hopital Claude Huriez- service de Médecine Interne
      • Lyon, France, 69000
        • Hopital de la Croix Rousse- service de Médecine Interne
      • Marseille, France, 13000
        • Hopital de la Timone- service de Médecine Internne
      • Nantes, France, 44000
        • CHU Hotel Dieu - service de Médecine Interne
      • Paris, France, 75013
        • GH la Pitié Salpêtrière. Service de Médecine interne
      • Paris, France, 75018
        • Hopital BICHAT - Médecine Interne
      • Paris, France, 75018
        • Hopital Bichat- service de pneumologie
      • Strasbourg, France, 67000
        • Nouvel Hopital Civil- service de Médecine Interne

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Clinical and radiological presentation confirming sarcoidosis
  • Presence of non caseating granuloma in at least one organ
  • Presence of at least one extrathoracic localization, including hypercalcemia
  • Exclusion of other causes of granuloma
  • Presence of serious organ involvement or relapse/apparition of a new localization despite a first-line immunosuppressive drug
  • Age superior or equal to 18 years

Exclusion Criteria:

  • Pregnancy or breast feeding or women in age of pregnancy without efficient contraception
  • Patients with multiple sclerosis
  • Patients with prior history of any cancer in the 5 years before inclusion (except for cutaneous basocellular cancers),
  • Patients with a history of hypersensitivity to infliximab to other murine proteins, or to any of the excipients
  • Patients with untreated tuberculosis or current other severe infections such as sepsis, abscesses, and opportunistic infections• Patients with moderate or severe heart failure (NYHA class III/IV)
  • Concurrent vaccination with live vaccines during therapy
  • Inability to understand information about the protocol
  • Adult subject under legal protection or unable to consent.
  • No informed consent
  • Absence of affiliation to National French social security system
  • Patients with severe renal failure, severe hepatic impairment, hepatocellular insufficiency, chronic respiratory insufficiency, risk of angle closure glaucoma, risk of urinary retention related to urethroprostatic disorders, certain evolving viral diseases (including hepatitis, herpes, varicella, zoster), psychotic states still not controlled by treatment

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: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: INFLIXIMAB
Infliximab 5 mg/kg D1-D15, then infliximab every 4 weeks W6-W10-W14
Drug: Infliximab
An initial period with 2 injections with infliximab allowing the determination of the primary criteria Then an extension with infliximab with 3 supplementary perfusions
Other: Placebo
placebo injection D1-D15 then infliximab 5 mg/kg W6-W8-W12-W16-W20
Drug: Placebo
An initial period with 2 injections with placebo allowing the determination of the primary criteria Then an extension with infliximab with 5 supplementary perfusions

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percentage of patients
Time Frame: week 6
who have a severity assessment score (ePOST score) inferior to 1 in all organs and absence of hypercalcemia at W6, whatever the corticosteroid dosage received
week 6

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percentage of patients
Time Frame: week 16 for experimental arm ; week 22 for control arm
who will have completed the steroid tapering regimen, will have a severity assessment score (ePOST score) < 1 in all organs, absence of hypercalcemia, had not have a relapse or any reason for treatment failure
week 16 for experimental arm ; week 22 for control arm
Mean variation in severity assessment score measured by extrapulmonary Physician Organ Severity Tool (ePOST)
Time Frame: Week 6
ePOST score will be assessed by the physician in charge of the patient. This score reflects the sarcoidosis activity in 17 organs and has been validated in previous studies : Skin, Peripheral lymph nodes, Eyes, Liver, Spleen, Central nervous system, Peripheral nervous system, Parotid/salivary glands, Bone marrow, Ear, Nose, Throat, Cardiac, Renal, Bone/joint, Muscle, Gastrointestinal. For each organ, a score will : 0 as Not affected, 1 as Slight, 2 as Mild, 3 as Moderate, 4 as Moderate to severe, 5 as Severe and 6 as Very severe. Total score is the sum of score in each organ.
Week 6
Pulmonary sarcoidosis involvement
Time Frame: Week 6
Pulmonary sarcoidosis involvement will be assessed by the physician in charge of the patient rated as: 0 as Not affected, 1 as Slight, 2 as Mild, 3 as Moderate, 4 as Moderate to severe, 5 as Severe and 6 as Very severe.
Week 6
Pulmonary sarcoidosis involvement 2 weeks after the 5th injection
Time Frame: week 16 for experimental arm ; week 22 for control arm
Pulmonary sarcoidosis involvement will be assessed by the physician in charge of the patient rated as: 0 as Not affected, 1 as Slight, 2 as Mild, 3 as Moderate, 4 as Moderate to severe, 5 as Severe and 6 as Very severe.
week 16 for experimental arm ; week 22 for control arm
Severity assessment score measured by ePOST 2 weeks after the 5th injection
Time Frame: week 16 for experimental arm ; week 22 for control arm
ePOST score will be assessed by the physician in charge of the patient. This score reflects the sarcoidosis activity in 17 organs and has been validated in previous studies : Skin, Peripheral lymph nodes, Eyes, Liver, Spleen, Central nervous system, Peripheral nervous system, Parotid/salivary glands, Bone marrow, Ear, Nose, Throat, Cardiac, Renal, Bone/joint, Muscle, Gastrointestinal. For each organ, a score will : 0 as Not affected, 1 as Slight, 2 as Mild, 3 as Moderate, 4 as Moderate to severe, 5 as Severe and 6 as Very severe. Total score is the sum of score in each organ
week 16 for experimental arm ; week 22 for control arm
Mean variation in the severity assessment score measured by ePOST from 1st injection (W0 or W6) to 2 weeks after the 5th injection
Time Frame: week 16 for experimental arm ; week 22 for control arm
ePOST score will be assessed by the physician in charge of the patient. This score reflects the sarcoidosis activity in 17 organs and has been validated in previous studies : Skin, Peripheral lymph nodes, Eyes, Liver, Spleen, Central nervous system, Peripheral nervous system, Parotid/salivary glands, Bone marrow, Ear, Nose, Throat, Cardiac, Renal, Bone/joint, Muscle, Gastrointestinal. For each organ, a score will : 0 as Not affected, 1 as Slight, 2 as Mild, 3 as Moderate, 4 as Moderate to severe, 5 as Severe and 6 as Very severe. Total score is the sum of score in each organ.
week 16 for experimental arm ; week 22 for control arm
Mean variation of quality of life measured by SF-36
Time Frame: Week 6
The SF-36 questionnaire is a quality of life questionnaire that includes 36 questions divided into 8 different categories (physical functioning, limitations due to physical condition, physical pain, perceived health, vitality, social functioning or well-being, limitations due to mental condition, mental health). It is self-administered and takes less than 10 minutes. Higher scores indicate better quality of life. Score from 0 to 100.
Week 6
Mean variation of fatigue, measured by the Fatigue Scale (FAS)
Time Frame: Week 6
The total score ranges from 10 to 50. A total FAS score < 22 indicates no fatigue, a score ≥ 22 indicates fatigue
Week 6
Mean variation of quality of life measured by SF-36
Time Frame: week 16 for experimental arm ; week 22 for control arm
The SF-36 questionnaire is a quality of life questionnaire that includes 36 questions divided into 8 different categories (physical functioning, limitations due to physical condition, physical pain, perceived health, vitality, social functioning or well-being, limitations due to mental condition, mental health). It is self-administered and takes less than 10 minutes. Higher scores indicate better quality of life. Score from 0 to 100.
week 16 for experimental arm ; week 22 for control arm
Mean variation of fatigue, measured by the Fatigue Scale (FAS)
Time Frame: week 16 for experimental arm ; week 22 for control arm
The total score ranges from 10 to 50. A total FAS score < 22 indicates no fatigue, a score ≥ 22 indicates fatigue
week 16 for experimental arm ; week 22 for control arm
Rate of relapses
Time Frame: week 16 for experimental arm ; week 22 for control arm
A relapse will be defined by the apparition of a new localization or a majoration of the severity assessment score from the previous assessment in at least one organ among the 17 studied in the ePOST score, after a previous 1 point or more decrease without hypercalcemia.
week 16 for experimental arm ; week 22 for control arm

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Assistance Publique - Hôpitaux de Paris

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Fleur COHEN AUBART, MCU-PH, APHP - Hôpital Pitié-Salpêtriere, Paris,France

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 28, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 21, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 28, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 10, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 12, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 15, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 7, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 5, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • P141205J
  • 2017-001809-32 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The procedures carried out with the French data privacy authority (CNIL, Commission nationale de l'informatique et des libertés) do not provide for the transmission of the database, nor do the information and consent documents signed by the patients.

Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations

IPD Sharing Time Frame

Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor

IPD Sharing Access Criteria

Researchers who provide a methodologically sound proposal.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

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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