This is a three-period study, with an open-label, single-arm active treatment in Period 1 followed by a randomized-withdrawal, double-blinded, placebo-controlled design in Period 2, and an open label, long-term safety follow-up in Period 3. The total study duration is approximately 3 - 4 years.

During Period 2, subjects will be randomized to MAS825 or matching placebo in a 1:1 ratio.

This study includes:

• Screening Period of approximately 30 days.
• Baseline Period
• Period 1. Open-Label Treatment Period to identify responders to MAS825. Period 1 is divided into 3 sub-parts:
• Period 1a, a 4-week treatment phase to stabilize patients on MAS825 treatment.
• Period 1b, a 20-week phase to gradually taper the dose of concomitant glucocorticoid treatment and discontinue cyclosporin treatment while on continued MAS825 treatment.
• Period 1c, a 4-week phase to maintain patients on stable low doses of glucocorticoids while on continued MAS825 treatment.
• Period 2. Randomized Withdrawal Period consists of a 24-week randomized treatment withdrawal period to primarily assess the efficacy of MAS825 compared to placebo.
• Period 3. Long-Term Safety, Open-Label Treatment consists of a 3-year long term-safety, open-label treatment with MAS825 following withdrawal or completion of Period 2.
• End of Study / Safety Follow-up: will be performed 16 weeks after the last dose.

Inclusion Criteria:

1. Male and female patients aged ≤ 17 years weighing at least 3 kg
2. Written informed consent by parent(s)/legal guardian(s) for the pediatric patients and assent by the pediatric patient (depending on local requirements) must be obtained before any study-specific assessment is performed.
3. Patients with genetic diagnosis of NLRC4-GOF
4. Clinical history and investigations consistent with autoinflammation with infantile enterocolitis (AIFEC/NLRC4-GOF)
5. At first treatment, evidence of active disease

Exclusion Criteria:

1. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes or to any of the excipients.
2. Signs and symptoms, in the judgment of the investigator, of clinically significant systemic recurrent and/or evidence of active bacterial, fungal, parasitic or viral infections.

   - COVID-19 specific: If in line with health and governmental authority guidance, it is highly recommended that testing to exclude COVID-19 using PCR or comparable approved methodology be completed within 1 week prior to first dosing.

3. Any conditions or significant medical problems, which in the opinion of the investigator places the patient at unacceptable risk for MAS825 therapy
4. Previous treatment with anti-rejection and/or immunomodulatory drugs within the past 28 days or 5 half-lives (whichever is the longer) for immunomodulatory therapeutic antibodies (or as listed in the prohibited medications section) prior to MAS825 treatment with thewith the exceptions of glucocorticoids, cyclosporin and targeted binding or blocking therapies.
5. A positive HIV test result at Screening. Evidence of prior testing within 3 months is sufficient.A positive HIV test result at Screening. Evidence of prior testing within 3 months is sufficient.
6. A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result. Evidence of prior testing within 3 months is sufficient.
7. Presence of tuberculosis infection as defined by a positive TB test at Screening. Evidence of prior testing within 3 months is sufficient.
8. Live vaccinations within 1 month prior to MAS825 treatment, during the trial, and up to 3 months following the last dose.
9. Female patients of child-bearing potential (or Tanner stage 2 or above) who are or might become sexually active, Female patients of child-bearing potential (or Tanner stage 2 or above) who are or might become sexually active, agree to use highly effective contraceptive methods to prevent pregnancy while on MAS825 therapy

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com