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)
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT04641442 |
|
Recruitment Status :
Recruiting
First Posted : November 23, 2020
Last Update Posted : April 12, 2024
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| NLRC4-GOF, AIFEC (Autoinflammation With Infantile Enterocolitis), XIAP Deficiency, CDC42 Mutations | Biological: MAS825 Biological: Placebo | Phase 2 |
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 (Clinical Trial) |
| Estimated Enrollment : | 18 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | This study includes:
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 only after completing screening and baseline assessments. |
| Masking: | Triple (Participant, Care Provider, Investigator) |
| Masking Description: | Subject, investigator, and sponsor blinding via manual randomization during Period 2, Randomized Withdrawal Period |
| Primary Purpose: | Treatment |
| Official Title: | 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 |
| Actual Study Start Date : | December 18, 2020 |
| Estimated Primary Completion Date : | June 27, 2025 |
| Estimated Study Completion Date : | September 16, 2028 |
| Arm | Intervention/treatment |
|---|---|
|
Experimental: MAS825
Experimental drug
|
Biological: MAS825
Experimental drug |
|
Placebo Comparator: Placebo
matching placebo
|
Biological: Placebo
matching placebo |
- 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
- 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
- All cohorts: Confirmation of serological markers of MAS825 [ Time Frame: Day 1 through EOS ]Evaluate the serological markers of MAS825
- 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
- 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
- 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
- Cohort 1: Time to first flare [ Time Frame: Period 2 ]Evaluate effect of MAS825 on the time to first flare
- 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
- 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | Child, Adult, Older Adult |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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 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).
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.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04641442
| Contact: Novartis Pharmaceuticals | 1-888-669-6682 | novartis.email@novartis.com | |
| Contact: Novartis Pharmaceuticals | +41613241111 |
Show 24 study locations
| Responsible Party: | Novartis Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT04641442 |
| Other Study ID Numbers: |
CMAS825D12201 |
| First Posted: | November 23, 2020 Key Record Dates |
| Last Update Posted: | April 12, 2024 |
| Last Verified: | April 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| 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 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
|
NLRC4-GOF AIFEC enterocolitis autoinflammation |
MAS NLRC4 (SCAN4) XIAP deficiency CDC42 mutations |
|
Enterocolitis Lymphoproliferative Disorders Genetic Diseases, X-Linked Gastroenteritis Gastrointestinal Diseases Digestive System Diseases |
Intestinal Diseases Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Genetic Diseases, Inborn |