At a glance
ClinicalIndex Comparison Record- ✓Genetic diagnosis of NLRC4-MAS mutation or XIAP deficiency (BIRC4 gene mutation) confirmed by central genetics laboratory
- ✓Evidence of inflammatory activity: ferritin ≥500 ng/mL OR persistent CRP elevation ≥2x ULN with mAIDAI ≥4
- ✓XIAP-deficient patients with prior bone marrow transplantation allowed if evidence of graft failure or XIAP-related disease recurrence with mixed chimerism
- ✓May be on corticosteroids, NSAIDs, DMARDs, or IL-1 blockade with insufficient response, or on no such treatments
- ✕Life-threatening comorbidities not associated with NLRC4-MAS or XIAP deficiency
- ✕HIV, Hepatitis B, or Hepatitis C seropositivity or prior history
- ✕Active infections, pulmonary tuberculosis (with or without adequate prior therapy)
- ✕Life-threatening infections
Standardized by ClinicalIndex from the ClinicalTrials.gov record · verify against the source.
Multicenter, Double-blind, Placebo-controlled, Randomized Withdrawal Trial With Tadekinig Alfa (r-hIL-18BP) in Patients With IL-18 Driven Monogenic Autoinflammatory Conditions: NLRC4 Mutation and XIAP Deficiency
In Brief
A Phase 3 clinical trial evaluating Tadekinig alfa and 0.9% sodium chloride for NLRC4-MAS and XIAP Deficiency. Completed, enrolled 15 participants across 9 sites in 3 countries.
Detailed Summary
This is a Phase 3 study to assess the safety and efficacy of Tadekinig alfa in patients with monogenic, interleukin-18 (IL 18) driven autoinflammation due to Nucleotide-binding oligomerization domain, leucine-rich repeat and caspase recruiting domain (CARD domain) containing 4 (NLRC4) - Macrophage activation syndrome (MAS) mutation (NLRC4-MAS mutation) or X-linked inhibitor of apoptosis (XIAP) deficiency. Because of the likelihood for pathogenic IL-18 in certain monogenic diseases, patients known to harbor deleterious mutations in NLRC4-MAS or XIAP and who have a history of ongoing inflammation will be enrolled if they have ferritin ≥ 500 ng/mL or persistent C reactive protein (CRP) elevation ≥ 2 times the upper limit of normal (ULN) and the patients should have a Modified Autoinflammatory Disease Activity Index (mAIDAI) ≥ 4.
Study Details
Timeline
Interventions
Tadekinig alfa is a soluble glycoprotein of 164 amino acids produced from Chinese Hamster Ovary cell line. Tadekinig alfa is supplied as a colorless to slightly yellow, sterile solution for injection in glass vials containing sodium chloride, and 0.02M sodium phosphate buffer as excipients. It is available in a concentration of 20mg/0.5mL.
To ensure that the treatment remains blinded for the entire study period, the placebo solutions will be supplied in identical vials and similar labelling as the active drug and will be indistinguishable in terms of their texture, color, and smell.