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

NCT03704610 | Completed Phase 3

• 2 other identifiers: P141205J2017-001809-32
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 10

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.

Conditions

Extrathoracic Sarcoidosis

Keywords

sarcoidosis; extra-thoracic; infliximab

Outcome Measures

Primary Outcomes (1)

• 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

  week 6

Secondary Outcomes (11)

• Percentage of patients

  week 16 for experimental arm ; week 22 for control arm

• Mean variation in severity assessment score measured by extrapulmonary Physician Organ Severity Tool (ePOST)

  Week 6

• Pulmonary sarcoidosis involvement

  Week 6

• Pulmonary sarcoidosis involvement 2 weeks after the 5th injection

  week 16 for experimental arm ; week 22 for control arm

• Severity assessment score measured by ePOST 2 weeks after the 5th injection

  week 16 for experimental arm ; week 22 for control arm

Study Arms (2)

INFLIXIMAB

EXPERIMENTAL

Infliximab 5 mg/kg D1-D15, then infliximab every 4 weeks W6-W10-W14

Drug: Infliximab

Placebo

OTHER

placebo injection D1-D15 then infliximab 5 mg/kg W6-W8-W12-W16-W20

Drug: Placebo

Interventions

Infliximab DRUG

An initial period with 2 injections with infliximab allowing the determination of the primary criteria Then an extension with infliximab with 3 supplementary perfusions

INFLIXIMAB

Placebo DRUG

An initial period with 2 injections with placebo allowing the determination of the primary criteria Then an extension with infliximab with 5 supplementary perfusions

Placebo

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• Pregnancy or breast feeding or women in age of pregnancy without efficient contraception
• Patients with multiple sclerosis
• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (10)

Hopital Avicenne - service de pnaumologie

Bobigny, 93000, France

Location

Hopital Henri Mondor- service de Médecine Interne

Créteil, 94000, France

Location

Hopital Claude Huriez- service de Médecine Interne

Lille, 59000, France

Location

Hopital de la Croix Rousse- service de Médecine Interne

Lyon, 69000, France

Location

Hopital de la Timone- service de Médecine Internne

Marseille, 13000, France

Location

CHU Hotel Dieu - service de Médecine Interne

Nantes, 44000, France

Location

GH la Pitié Salpêtrière. Service de Médecine interne

Paris, 75013, France

Location

Hopital BICHAT - Médecine Interne

Paris, 75018, France

Location

Hopital Bichat- service de pneumologie

Paris, 75018, France

Location

Nouvel Hopital Civil- service de Médecine Interne

Strasbourg, 67000, France

Location

MeSH Terms

Conditions

Sarcoidosis

Interventions

Infliximab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Fleur COHEN AUBART, MCU-PH

  APHP - Hôpital Pitié-Salpêtriere, Paris,France

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2018
• First Posted: October 15, 2018
• Study Start: March 28, 2019
• Primary Completion: June 21, 2021
• Study Completion: September 28, 2021
• Last Updated: February 7, 2024

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• 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
• Access Criteria: Researchers who provide a methodologically sound proposal.

Locations

FR (10)