Therapeutic Use of Tadekinig Alfa in NLRC4 Mutation and XIAP Deficiency

The study is designed with single-arm, open-label phase (SAOL) of Tadekinig alfa treatment
duration for 18-week followed by an 8-week Randomized Withdrawal (RW) period for efficacy and
safety evaluation, with no interruption between the two phases of treatment. The screening
period will occur before the SAOL phase and before the first dose of Investigational
Medicinal Product (IMP)

INCLUSION CRITERIA

1. Patients ≤ 17 years of age

2. Patients with genetic diagnosis of NLRC4-MAS mutation or XIAP deficiency (caused by
BIRC4 gene mutation)

3. Ferritin ≥ 500 ng/mL or persistent elevation of CRP ≥ 2x ULN and mAIDAI ≥4

4. Patients receiving stable doses of corticosteroids, non-steroidal anti-inflammatory
drugs (NSAIDs) or disease modifying anti rheumatic drugs (DMARDs), and/or IL-1
blockade for at least 2 weeks prior to enrollment are allowed into the study. Patients
not receiving any of these treatments before start of therapy are also allowed

5. Women of childbearing potential with negative urine pregnancy test (UPT) at all visits

EXCLUSION CRITERIA

1. Patients > 17 years of age

2. Positive test for or prior history of HIV, Hepatitis B or Hepatitis C (serology)

3. Presence of active infections or a history of pulmonary TB infection with or without
documented adequate therapy

4. Presence of life threatening infections

5. Oncologic causes of symptoms; current or previous history of malignancy

6. Presence of CNS manifestations

7. Patients suffering from familial hemophagocytic lymphohistiocytosis (f HLH)

8. Patients who are pregnant or nursing, women of childbearing potential who are
unwilling to use highly effective birth control methods

9. Concomitant use of immunosuppression therapies excluded by the protocol.

10. Patients and/or parents (or legal representative, if applicable) not willing to sign
assent/informed consent