Extrathoracic SarcoidosisPhase 3EFIRTESNCT03704610
Efficacy of Remission-induction Regimen With Infliximab for Severe Extrathoracic Sarcoidosis (EFIRTES)
A Phase 3 study testing Infliximab in people with Extrathoracic Sarcoidosis, run by Assistance Publique - Hôpitaux de Paris at 10 sites in France.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Extrathoracic Sarcoidosis
- What is being tested?
- Infliximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 31 participants
- Where
- 10 sitesFrance
- Study dates
- 28 Mar 2019to 28 Sep 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
France10 sites
Hopital Avicenne - service de pnaumologie
Bobigny, 93000
Hopital Henri Mondor- service de Médecine Interne
Créteil, 94000
Hopital Claude Huriez- service de Médecine Interne
Lille, 59000
Hopital de la Croix Rousse- service de Médecine Interne
Lyon, 69000
Hopital de la Timone- service de Médecine Internne
Marseille, 13000
CHU Hotel Dieu - service de Médecine Interne
Nantes, 44000
GH la Pitié Salpêtrière. Service de Médecine interne
Paris, 75013
Hopital BICHAT - Médecine Interne
Paris, 75018
Hopital Bichat- service de pneumologie
Paris, 75018
Nouvel Hopital Civil- service de Médecine Interne
Strasbourg, 67000
About this study
Official title: 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.
Read the 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.
- Conditions
- Extrathoracic Sarcoidosis
- Being tested
- Infliximab, Placebo
- Keywords
- sarcoidosis, extra-thoracic, infliximab
- Medical subject headings
- Sarcoidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
InfliximabDrug
An initial period with 2 injections with infliximab allowing the determination of the primary criteria Then an extension with infliximab with 3 supplementary perfusions
PlaceboDrug
An initial period with 2 injections with placebo allowing the determination of the primary criteria Then an extension with infliximab with 5 supplementary perfusions
| Study group | Role | What they receive |
|---|---|---|
| INFLIXIMAB | Experimental | Infliximab 5 mg/kg D1-D15, then infliximab every 4 weeks W6-W10-W14 Receives: Drug: Infliximab |
| Placebo | Other | placebo injection D1-D15 then infliximab 5 mg/kg W6-W8-W12-W16-W20 Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: week 6
Secondary outcomes (11)
Percentage of patients
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
Measured: week 16 for experimental arm ; week 22 for control arm
Mean variation in severity assessment score measured by extrapulmonary Physician Organ Severity Tool (ePOST)
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.
Measured: Week 6
Pulmonary sarcoidosis involvement
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.
Measured: Week 6
Pulmonary sarcoidosis involvement 2 weeks after the 5th injection
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.
Measured: week 16 for experimental arm ; week 22 for control arm
Severity assessment score measured by ePOST 2 weeks after the 5th injection
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
Measured: 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
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.
Measured: week 16 for experimental arm ; week 22 for control arm
Mean variation of quality of life measured by SF-36
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.
Measured: Week 6
Mean variation of fatigue, measured by the Fatigue Scale (FAS)
The total score ranges from 10 to 50. A total FAS score < 22 indicates no fatigue, a score ≥ 22 indicates fatigue
Measured: Week 6
Mean variation of quality of life measured by SF-36
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.
Measured: week 16 for experimental arm ; week 22 for control arm
Mean variation of fatigue, measured by the Fatigue Scale (FAS)
The total score ranges from 10 to 50. A total FAS score < 22 indicates no fatigue, a score ≥ 22 indicates fatigue
Measured: week 16 for experimental arm ; week 22 for control arm
Rate of relapses
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.
Measured: week 16 for experimental arm ; week 22 for control arm
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2018
- Study start28 Mar 2019
- Primary completion21 Jun 2021
- Study completion28 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Extrathoracic SarcoidosisStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Fleur COHEN AUBART, MCU-PH, Study director, APHP - Hôpital Pitié-Salpêtriere, Paris,France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03704610
- Sponsor's protocol ID
- P141205J
- Other IDs
- 2017-001809-32, 2017
- Acronym
- EFIRTES
- Status last verified
- Oct 2023
- First submitted
- 10 Oct 2018
- Last updated
- 7 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Remission-induction Regimen With Infliximab for Severe Extrathoracic Sarcoidosis (EFIRTES STUDY)
- ClinicalTrials.gov ID
- NCT03704610
- Acronym / sponsor ID
- EFIRTES / P141205J
- Conditions
- Extrathoracic Sarcoidosis
- Keywords
- sarcoidosis, extra-thoracic, infliximab
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 28 Mar 2019 (actual)
- Primary completion
- 21 Jun 2021 (actual)
- Study completion
- 28 Sep 2021 (actual)
- First posted
- 15 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| INFLIXIMAB | Experimental | Drug: InfliximabInfliximab 5 mg/kg D1-D15, then infliximab every 4 weeks W6-W10-W14 |
| Placebo | Other | Drug: Placeboplacebo injection D1-D15 then infliximab 5 mg/kg W6-W8-W12-W16-W20 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (13 listed)
- 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
- 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),
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| InfliximabAn initial period with 2 injections with infliximab allowing the determination of the primary criteria Then an extension with infliximab with 3 supplementary perfusions | Drug | INFLIXIMAB |
| PlaceboAn initial period with 2 injections with placebo allowing the determination of the primary criteria Then an extension with infliximab with 5 supplementary perfusions | Drug | Placebo |
Primary outcome
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
11 secondary outcomes
Percentage of patients
Time frame: 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
Pulmonary sarcoidosis involvement
Time frame: Week 6
Pulmonary sarcoidosis involvement 2 weeks after the 5th injection
Time frame: 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
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
Mean variation of quality of life measured by SF-36
Time frame: Week 6
Mean variation of fatigue, measured by the Fatigue Scale (FAS)
Time frame: Week 6
Mean variation of quality of life measured by SF-36
Time frame: 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
Rate of relapses
Time frame: week 16 for experimental arm ; week 22 for control arm
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2024.
- Individual participant dataSharing planned: Yes. 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
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Fleur COHEN AUBART, MCU-PH study director
APHP - Hôpital Pitié-Salpêtriere, Paris,France
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Infliximab in people with Extrathoracic Sarcoidosis, run by Assistance Publique - Hôpitaux de Paris at 10 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of patients (time frame: week 6). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Feb 2024.