Efficacy of Remission-induction Regimen With Infliximab for Severe Extrathoracic Sarcoidosis (EFIRTES STUDY)
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Enrollment
- 31
- Locations
- 10
- Primary Endpoint
- Percentage of patients
Study Overview
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.
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).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- 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.
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
INFLIXIMAB
Infliximab 5 mg/kg D1-D15, then infliximab every 4 weeks W6-W10-W14
Intervention: Infliximab (Drug)
Placebo
placebo injection D1-D15 then infliximab 5 mg/kg W6-W8-W12-W16-W20
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
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
Secondary Outcomes
- Mean variation in severity assessment score measured by extrapulmonary Physician Organ Severity Tool (ePOST)(Week 6)
- Pulmonary sarcoidosis involvement(Week 6)
- Percentage of patients(week 16 for experimental arm ; week 22 for control arm)
- Mean variation of quality of life measured by SF-36(week 16 for experimental arm ; week 22 for control arm)
- Rate of relapses(week 16 for experimental arm ; week 22 for control arm)
- 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)
- Mean variation in the severity assessment score measured by ePOST from 1st injection (W0 or W6) to 2 weeks after the 5th injection(week 16 for experimental arm ; week 22 for control arm)
- Mean variation of fatigue, measured by the Fatigue Scale (FAS)(week 16 for experimental arm ; week 22 for control arm)