Pivotal trial
Study design for MAS in Still's disease
Studied in patients with high unmet need
Data evaluating the efficacy and safety of Gamifant were pooled across 2 open-label, single-arm, multicenter studies of 39 patients who had hemophagocytic lymphohistiocytosis (HLH)/macrophage activation syndrome (MAS) in Still’s disease, including systemic juvenile idiopathic arthritis (sJIA), with an inadequate response to high-dose glucocorticoid (GC) treatment.1
Study information1,2
Trial design | Two open-label, single-arm, multicenter, phase 2/3 studies |
Study duration | Up to 8 weeks |
No. of patients | 39 (31 female, 8 male) |
Age | |
Median | 12 years (range: 9 months-64 years) |
Breakdown (n) | <2 years (3) |
Key efficacy measure1
The key efficacy measure of the pivotal trials was complete response at week 8.
Complete response at week 81
CR | An 8-component composite endpoint that included normalization of 7 laboratory parameters and clinical MAS remission measured by the clinician’s assessment (visual analog scale [VAS] ≤1/10 cm).1 |
PR | A VAS <4/10 cm and normalization of at least 3 of the abnormal baseline laboratory parameters relevant to MAS.1 |
OR | Achievement of a complete or partial response.1 |
The composite endpoint included assessment of a broad range of active MAS manifestations1
In the pooled analysis, the efficacy of Gamifant was evaluated based on an 8-component composite endpoint complete response (CR) at week 8.1
- WBC > LLN
- Platelet count > LLN
- LDH <1.5 x ULN
- ALT <1.5 x ULN
- AST <1.5 x ULN
- Fibrinogen >100 mg/dL
- Ferritin reduced by ≥80% from baseline or <2000 ng/mL, whichever is lower
Clinician's assessment:
- Clinical MAS remission (VAS ≤1/10 cm)
ALT=alanine aminotransferase; AST=aspartate aminotransferase; LDH=lactate dehydrogenase; LLN=lower limit of normal; ULN=upper limit of normal; WBC=white blood cell.
MAS clinical activity at week 8: Clinical MAS remission was assessed using a visual analog scale (VAS) where 0 cm referred to no clinical signs or symptoms of MAS and 10 cm referred to the worst possible clinical signs and symptoms of MAS.1
The clinical signs and symptoms evaluated by the treating physician to assess MAS activity included:
- Fever >100.4°F
- Skin rash
- Hemorrhagic manifestations
- Skin bleeding (petechiae, ecchymosis, or purpura)
- Mucosal bleeding (gut or respiratory)
- CNS involvement
- Headache, irritability, seizures, confusion, lethargy, coma
- CSF abnormalities
- Respiratory function (need for oxygen support or mechanical ventilation)
- Cardiac function
- Pericarditis
- Inotropic support
- Kidney ultrafiltration/dialysis
CNS=central nervous system; CSF=cerebrospinal fluid.