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

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Completed

CT.gov ID

NCT03704610

Collaborator

(none)

Enrollment

Locations

Arms

30.1

Actual Duration (Months)

3.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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 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.

Condition or Disease	Intervention/Treatment	Phase
Extrathoracic Sarcoidosis	Drug: Infliximab Drug: Placebo	Phase 3

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

Study Type:

Interventional

Actual Enrollment :

31 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Masking Description:

Only the two first infusions will be blinded. Treatment will be prepared by local pharmacies. The pharmacist will receive a fax with the treatment to prepare (infliximab or placebo). The placebo will be an injectable solution of 0.9% sodium chloride equivalent to the one used for infliximab reconstitution. Both treatments will be presented in an infusion bag. After reconstitution and dilution, infliximab solution is clear and limpid, similar to 0.9% sodium chloride solution. At week 6, after evaluation of ePOST score, unblinding process will be done. All the patients will receive infliximab treatment.

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 28, 2019

Actual Primary Completion Date :

Jun 21, 2021

Actual Study Completion Date :

Sep 28, 2021

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

Percentage of patients [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

Secondary Outcome Measures

Percentage of patients [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Hopital Avicenne - service de pnaumologie	Bobigny	France	93000
2	Hopital Henri Mondor- service de Médecine Interne	Créteil	France	94000
3	Hopital Claude Huriez- service de Médecine Interne	Lille	France	59000
4	Hopital de la Croix Rousse- service de Médecine Interne	Lyon	France	69000
5	Hopital de la Timone- service de Médecine Internne	Marseille	France	13000
6	CHU Hotel Dieu - service de Médecine Interne	Nantes	France	44000
7	GH la Pitié Salpêtrière. Service de Médecine interne	Paris	France	75013
8	Hopital BICHAT - Médecine Interne	Paris	France	75018
9	Hopital Bichat- service de pneumologie	Paris	France	75018
10	Nouvel Hopital Civil- service de Médecine Interne	Strasbourg	France	67000

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators

Study Director: Fleur COHEN AUBART, MCU-PH, APHP - Hôpital Pitié-Salpêtriere, Paris,France

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Assistance Publique - Hôpitaux de Paris

ClinicalTrials.gov Identifier:

NCT03704610

Other Study ID Numbers:

P141205J
2017-001809-32

First Posted:

Oct 15, 2018

Last Update Posted:

Nov 16, 2021

Last Verified:

Nov 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Assistance Publique - Hôpitaux de Paris

sarcoidosis

extra-thoracic

infliximab

Additional relevant MeSH terms:

Sarcoidosis

Infliximab

Study Results

No Results Posted as of Nov 16, 2021