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

NCT04641442 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CMAS825D12201
• Study Type: interventional
• Target: 17
• Locations: 7 countries
• Sites: 21

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.

Conditions

NLRC4-GOF, AIFEC (Autoinflammation With Infantile Enterocolitis), XIAP Deficiency, CDC42 Mutations

Keywords

NLRC4-GOF; AIFEC; enterocolitis; autoinflammation; MAS; NLRC4 (SCAN4); XIAP deficiency; CDC42 mutations

Outcome Measures

Primary Outcomes (1)

• 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

  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

  Period 2

Secondary Outcomes (8)

• All cohorts: Number and severity of safety assessments and adverse events

  Screening through EOS (End of Study)

• 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

Study Arms (2)

MAS825

EXPERIMENTAL

Experimental drug

Biological: MAS825

Placebo

PLACEBO COMPARATOR

matching placebo

Biological: Placebo

Interventions

MAS825 BIOLOGICAL

Experimental drug

MAS825

Placebo BIOLOGICAL

matching placebo

Placebo

Eligibility Criteria

• Age: 0 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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
• 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).

You may not qualify if:

• 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.
• 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
• Patients weighing \>160 kg at Screening.
• For CDC42 mutation patients: Takenouchi-Kosaki syndrome - CDC42 mutations associated with a diverse syndrome characterized by variable development delays, cardiac, brain and hematological abnormalities.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (21)

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

Cincinnati Childrens Hospital

Cincinnati, Ohio, 45229, United States

Location

Childrens Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104-4399, United States

Location

Children´s Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Texas Childrens Hospital

Houston, Texas, 77030, United States

Location

Texas Children´s Hospital

Houston, Texas, 77030, United States

Location

Seattle Childrens Hospital

Seattle, Washington, 98105, United States

Location

Seattle Children´s Hospital

Seattle, Washington, 98105, United States

Location

Centrum detske revmatologie a autoinflamatornich onemocneni

Prague, CZ, 121 00, Czechia

Location

Novartis Investigative Site

Prague, 128 08, Czechia

Location

Novartis Investigative Site

Prague, 150 06, Czechia

Location

Ustav Imunologie 2 LF UK a FN Motol

Prague, 150 06, Czechia

Location

Novartis Investigative Site

Paris, 75970, France

Location

Bambino Gesu Hospital

Roma, RM, 00165, Italy

Location

Novartis Investigative Site

Roma, RM, 00165, Italy

Location

Novartis Investigative Site

Chiba, 266-0007, Japan

Location

Hospital Clinic Barcelona

Barcelona, Catalonia, 08036, Spain

Location

Novartis Investigative Site

Madrid, 28046, Spain

Location

Novartis Investigative Site

London, NW3 2QG, United Kingdom

Location

Great Ormond Street Hospital

London, WC1N 3JH, United Kingdom

Location

Novartis Investigative Site

London, WC1N 3JH, United Kingdom

Location

MeSH Terms

Conditions

Lymphoproliferative Syndrome, X-Linked, 2; Enterocolitis

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Subject, investigator, and sponsor blinding via manual randomization during Period 2, Randomized Withdrawal Period
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This study includes: * Screening * Period 1: Open-Label Treatment Period to identify responders to MAS825 * Period 2: Randomized Withdrawal Period consists of a randomized treatment withdrawal period to primarily assess the efficacy of MAS825 compared to placebo. * Period 3: Open-Label, Long-Term Safety follow-up * Period 3s: Open-Label, transition to new route of administration and safety follow-up * End of Study Patients will participate in all 3 periods of the study if they have never been treated with MAS825 before. Patients who are enrolled from the Managed Access program will participate in Period 3 and Period 3s only after completing screening and baseline assessments.

Study Record Dates

• First Submitted: November 20, 2020
• First Posted: November 23, 2020
• Study Start: December 18, 2020
• Primary Completion: October 14, 2025
• Study Completion (Estimated): April 7, 2032
• Last Updated: March 3, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

IT (2); JP (1); FR (1); CZ (4); ES (2); GB (3); US (8)