P090 Protocol for the two-cohort, open-label, single-arm EMERALD study of emapalumab, an anti-interferon gamma monoclonal antibody, in patients with macrophage activation syndrome in rheumatic diseases
Authors: Brogan Paul , Grom Alexei , Kanceva Radmila , De Benedetti Fabrizio 
Published: April 2023

Background/Aims

Macrophage activation syndrome (MAS), a form of secondary haemophagocytic lymphohistiocytosis, is a severe, life-threatening complication of rheumatic diseases such as Still’s disease (systemic juvenile idiopathic arthritis or adult-onset Still’s disease) and systemic lupus erythematosus (SLE). Interferon gamma has been implicated in the underlying pathology of both conditions. Standard first-line treatment for MAS is high-dose glucocorticoids (GCs); however, additional treatments are used without a standardised approach in patients who are treatment-refractory. When 9 patients with an inadequate response to high-dose GCs were administered emapalumab in a pilot study (NCT03311854), interferon gamma was rapidly neutralised and MAS was controlled. Emapalumab also had a favourable safety profile. A new study (EMERALD) is currently enrolling patients with MAS in Still’s disease and SLE to further evaluate the efficacy and safety of emapalumab.

Methods

The open-label, single arm, multicentre, phase 2/3 interventional EMERALD study (NCT05001737) is enrolling paediatric and adult subjects with MAS and an inadequate response to high-dose GCs into two cohorts: MAS in Still’s disease (n = 25) and MAS in SLE (n = 16). Each cohort is a single-arm study comprising two phases: an optional run-in phase and an interventional phase. Key eligibility criteria vary by cohort and phase (Table). During the run-in phase, patients are treated with high-dose GCs and followed until MAS remission or inadequate response, or for a maximum of 12 weeks. Patients enrolled in the interventional phase are treated with intravenous emapalumab (initial dose 6 mg/kg, subsequent doses 3 mg/kg) for 4 weeks or until protocol-defined complete response (CR), then followed up for 1 year.

Results

The primary endpoint of the study is protocol-defined CR at Week 8 after first emapalumab administration. Secondary efficacy endpoints include GC tapering, survival, time to first CR, overall response (CR and partial response), time to first overall response, MAS recurrence, pharmacokinetic/pharmacodynamic profile of emapalumab and patient-reported outcomes. Safety endpoints include assessments of adverse events, abnormal laboratory parameters and anti-drug antibodies.

Conclusion

The ongoing EMERALD study is designed to address the unmet need for new efficacious and safe therapies for the treatment of MAS.

Disclosure

P. Brogan: Consultancies; P.B. has acted as a consultant for Sobi, Novartis, Roche and UCB. A. Grom: Consultancies; A.G. has acted as a consultant for Novartis, AB2 Bio, Novimmune and Sobi. R. Kanceva: Corporate appointments; R.K. is an employee of Sobi. F. De Benedetti: Consultancies; F.D.B. has acted as a consultant for AbbVie, Sobi, Pfizer, Roche, Sanofi, Novartis and Novimmune. Grants/research support; F.D.B has received research grants from AbbVie, Sobi, Pfizer, Roche, Sanofi, Novartis and Novimmune.