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)

April 11, 2024 updated by: Novartis Pharmaceuticals

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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. 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.

Study Type

Interventional

Enrollment (Estimated)

18

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Novartis Pharmaceuticals
  • Phone Number: +41613241111

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • Recruiting
        • Novartis Investigative Site
    • Quebec
      • Montreal, Quebec, Canada, H3T 1C5
  • Czechia
      • Prague 5, Czechia, 150 06
        • Recruiting
        • Ustav Imunologie 2 LF UK a FN Motol
        • Contact:
    • CZ
      • Praha, CZ, Czechia, 121 00
        • Recruiting
        • Centrum detske revmatologie a autoinflamatornich onemocneni
        • Contact:
        • Principal Investigator:
          • Pavla Dolezalova
  • France
      • Bordeaux Cedex, France, 33076
        • Recruiting
        • Novartis Investigative Site
      • Bron Cedex, France, 69677
        • Recruiting
        • Novartis Investigative Site
      • Nice, France, 06202
        • Recruiting
        • Novartis Investigative Site
      • Paris, France, 75970
        • Recruiting
        • Novartis Investigative Site
      • Paris 15, France, 75015
        • Recruiting
        • Novartis Investigative Site
  • Italy
    • RM
      • Roma, RM, Italy, 00165
        • Recruiting
        • Bambino Gesu Hospital
        • Contact:
        • Principal Investigator:
          • Fabrizio De Benedetti
  • Japan
    • Aichi
      • Obu, Aichi, Japan, 474 8710
        • Withdrawn
        • Novartis Investigative Site
    • Chiba
      • Chiba-city, Chiba, Japan, 266-0007
        • Recruiting
        • Novartis Investigative Site
    • Tokyo
      • Bunkyo-ku, Tokyo, Japan, 113-8519
        • Recruiting
        • Novartis Investigative Site
  • Spain
      • Madrid, Spain, 28046
        • Recruiting
        • Novartis Investigative Site
    • Catalunya
      • Barcelona, Catalunya, Spain, 08036
        • Recruiting
        • Hospital Clinic Barcelona
        • Contact:
        • Principal Investigator:
          • Xavier Bosch
    • Extremadura
      • Caceres, Extremadura, Spain, 10003
        • Recruiting
        • Hospital San Pedro de Alcántara
        • Contact:
        • Principal Investigator:
          • Luis Miguel Fernandez Pereira
  • Turkey
      • Ankara, Turkey, 06100
        • Recruiting
        • Novartis Investigative Site
      • Istanbul, Turkey, 34766
        • Recruiting
        • Novartis Investigative Site
    • TUR
      • Istanbul, TUR, Turkey, 34098
        • Recruiting
        • Novartis Investigative Site
  • United Kingdom
      • London, United Kingdom, WC1N 3JH
  • United States
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Recruiting
        • Cincinnati Children's Hospital
        • Contact:
        • Principal Investigator:
          • Alexei Grom
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • Children´s Hospital of Philadelphia
        • Contact:
    • Texas
      • Houston, Texas, United States, 77030
    • Washington
      • Seattle, Washington, United States, 98105

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

For all Patients:

  1. Male and female patients 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. 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:

  3. Patients with a genetic diagnosis of either NLRC4-GOF, XIAP deficiency, or CDC42 mutation
  4. 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.

  5. At first treatment, evidence of active disease as assessed by inflammatory markers and PGA

    Cohort 2 specific inclusion criteria:

  6. 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:

  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 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.

  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 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.
  6. A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result at Screening. 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. Pregnant or nursing (lactating) females.
  10. 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
  11. Patients weighing >160 kg at Screening.
  12. For CDC42 mutation patients: Takenouchi-Kosaki syndrome - CDC42 mutations associated with a diverse syndrome characterized by variable development delays, cardiac, brain and hematological abnormalities.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
matching placebo
Biological: Placebo
matching placebo
Experimental: MAS825
Experimental drug
Biological: MAS825
Experimental drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Period 2

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
All cohorts: Number and severity of safety assessments and adverse events
Time Frame: Screening through EOS (End of Study)
To evaluate the safety and tolerability of MAS825
Screening through EOS (End of Study)
All cohorts: Confirmation of serological markers of MAS825
Time Frame: Day 1 through EOS
Evaluate the serological markers of MAS825
Day 1 through EOS
Cohort 1: PGA and inflammatory markers
Time Frame: Day 29, end of Period 1, end of Period 2
Evaluate the efficacy of MAS825 to improve the clinical status of patients with NLRC4-GOF, XIAP deficiency or CDC42 mutations
Day 29, end of Period 1, end of Period 2
Cohort 1: Serological remission via inflammatory markers
Time Frame: Day 29, end of Period 1, and end of Period 2
Evaluate efficacy of MAS825 to achieve serological remission
Day 29, end of Period 1, and end of Period 2
Cohort 1: Glucocorticoid therapy <0.2mg/kg by end of period 1
Time Frame: End of Period 1
Evaluate the effect of MAS825 on concomitant glucocorticoid administration
End of Period 1
Cohort 1: Time to first flare
Time Frame: Period 2
Evaluate effect of MAS825 on the time to first flare
Period 2
All cohorts: Physician Severity Assessment of Disease Signs and Symptoms scale
Time Frame: Screening through EOS
Evaluate the efficacy of MAS825 to improve signs and symptoms of the disease
Screening through EOS
All cohorts: Patient / Parent global assessment of disease activity (PPGA) scale
Time Frame: Screening through EOS
Evaluate effect of MAS825 on patient reported outcomes over time
Screening through EOS

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 18, 2020

Primary Completion (Estimated)

June 27, 2025

Study Completion (Estimated)

September 16, 2028

Study Registration Dates

First Submitted

November 20, 2020

First Submitted That Met QC Criteria

November 20, 2020

First Posted (Actual)

November 23, 2020

Study Record Updates

Last Update Posted (Actual)

April 12, 2024

Last Update Submitted That Met QC Criteria

April 11, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CMAS825D12201

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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