A Three-period Multicenter Study, With a Randomized-withdrawal, Double-blind, Placebo-controlled Design to Evaluate the Clinical Efficacy, Safety and Tolerability of MAS825 in Patients With Monogenic IL-18 Driven Autoinflammatory Diseases, Including NLRC4-GOF, XIAP Deficiency, or CDC42 Mutations
Overview
- Phase
- Phase 2
- Intervention
- MAS825
- Conditions
- NLRC4-GOF, AIFEC (Autoinflammation With Infantile Enterocolitis), XIAP Deficiency, CDC42 Mutations
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 17
- Locations
- 24
- Primary Endpoint
- Cohort 1: Occurrence of disease flare in patients with MAS825 treated patients compared with placebo during Period 2 assessed by Physician's Global Assessment and inflammatory markers
- Status
- Active, not recruiting
- Last Updated
- 2 months ago
Overview
Brief Summary
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.
Detailed 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 and Period 3s. The total study duration is approximately 4 - 5 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 5 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 and Period 3s for open-label long-term safety follow-up. Cohort 2 patients will be in the study for approximately 4 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •For all Patients:
- •Male and female patients weighing at least 3 kg
- •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. For adult patients, written informed consent by patients capable of giving consent, or when the patient is not capable of giving consent, by his/her legal/authorized representative (if allowed according to local requirements).
- •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 CDC
- •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).
Exclusion Criteria
- •History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes or to any of the excipients.
- •Signs and symptoms, in the judgment of the investigator, of clinically significant active bacterial, fungal, parasitic or viral infections, excluding chronic Epstein-Barr Virus (EBV).
- •\- 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.
- •Any conditions or significant medical problems, which in the opinion of the investigator places the patient at unacceptable risk for MAS825 therapy
- •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 the exceptions of glucocorticoids, cyclosporin and targeted binding or blocking therapies.
- •A positive HIV test result at Screening. Evidence of prior testing within 3 months is sufficient.
- •A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result at Screening. Evidence of prior testing within 3 months is sufficient.
- •Presence of tuberculosis infection as defined by a positive TB test at Screening. Evidence of prior testing within 3 months is sufficient.
- •Live vaccinations within 1 month prior to MAS825 treatment, during the trial, and up to 3 months following the last dose.
- •Pregnant or nursing (lactating) females.
Arms & Interventions
MAS825
Experimental drug
Intervention: MAS825
Placebo
matching placebo
Intervention: Placebo
Outcomes
Primary Outcomes
Cohort 1: Occurrence of disease flare in patients with MAS825 treated patients compared with placebo during Period 2 assessed by Physician's Global Assessment and inflammatory markers
Time Frame: Period 2
To determine the efficacy of MAS825 in prevention of flares in patients with monogenic IL-18 driven autoinflammatory diseases, including NLRC4-GOF, XIAP deficiency or CDC42 mutations
Secondary Outcomes
- All cohorts: Number and severity of safety assessments and adverse events(Screening through EOS (End of Study))
- All cohorts: Physician Severity Assessment of Disease Signs and Symptoms scale(Screening through EOS)
- All cohorts: Patient / Parent global assessment of disease activity (PPGA) scale(Screening through EOS)
- All cohorts: Confirmation of serological markers of MAS825(Day 1 through EOS)
- Cohort 1: PGA and inflammatory markers(Day 29, end of Period 1, end of Period 2)
- Cohort 1: Serological remission via inflammatory markers(Day 29, end of Period 1, and end of Period 2)
- Cohort 1: Glucocorticoid therapy <0.2mg/kg by end of period 1(End of Period 1)
- Cohort 1: Time to first flare(Period 2)