Texas Children's Cancer and Hematology Center Study to Evaluate the Efficacy, Safety and Tolerability of MAS825 in Patients With Monogenic IL-18 Driven Autoinflammatory Diseases, Including NLRC4-GOF, XIAP Deficiency, or CDC42 Mutations (MASter-1) 

Diseases

This study is a Phase 2 trial designed to evaluate the clinical efficacy, safety, and tolerability of MAS825 in patients with NLRC4-GOF, XIAP deficiency, or CDC42 mutations.

Description

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.

Patients who enter Period 2 will be randomized to MAS825 or matching placebo in a 1:1 ratio.

Cohort 1 patients will complete all periods of the study, which will take approximately 4 years.

Cohort 2: Patients who are receiving MAS825 in a Novartis Managed Access Program with a diagnosis of NLRC4-GOF, XIAP deficiency, or CDC42 mutation who meet criteria will be eligible to directly enter into Period 3 for open-label long-term safety follow-up. Cohort 2 patients will be in the study for approximately 3 years.

Eligibility Criteria

• Must weigh at least 3 kg
• Ages Eligible for Study: Children, Adult, Older Adult
• Sexes Eligible for Study: All
• Cohort 1 specific inclusion criteria:
  • Patients with a genetic diagnosis of either NLRC4-GOF, XIAP deficiency, or CDC42 mutation
  • Clinical history and investigations consistent with autoinflammation and infantile enterocolitis (AIFEC/NLRC4-GOF), XIAP or CDC42. XIAP patients must have persistent disease or be resistant to escalating therapy.
  • At first treatment, evidence of active disease as assessed by inflammatory markers and PGA
• Cohort 2 specific inclusion criteria:
  • Patients with a genetic diagnosis of NLRC4-GOF, XIAP deficiency, or CDC42 mutations who are being treated with MAS825 in a Novartis Managed Access Program (MAP).

Detailed inclusion and exclusion criteria as listed on clinicaltrials.gov