MAS NLRC4-GOF: MASter-1 Study to Evaluate the Efficacy and Safety of MAS825 in NLRC4-GOF Patients

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04641442
• Collaborator: (none)
• Enrollment: 8
• Locations: 15
• Arms: 2
• Anticipated Duration (Months): 76.2
• Patients Per Site: 0.5
• Patients Per Site Per Month: 0

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
NLRC4-GOF, AIFEC (Autoinflammation With Infantile Enterocolitis)	Biological: MAS825; Biological: Placebo	Phase 2

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.

During Period 2, subjects will be randomized to MAS825 or matching placebo in a 1:1 ratio.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 8 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: 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 End of StudyThis 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 End of Study
• 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-blinded, Placebo-controlled Design in Period 2 to Evaluate the Clinical Efficacy, Safety, and Tolerability of MAS825 in NLRC4-GOF Patients
• Actual Study Start Date: Dec 18, 2020
• Anticipated Primary Completion Date: Feb 2, 2024
• Anticipated Study Completion Date: Apr 25, 2027

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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 [Period 2]

   To determine the efficacy of MAS825 in prevention of flares in NLRC4-GOF patients

Secondary Outcome Measures

1. Number and severity of safety assessments and adverse events [Screening through EOS (End of Study)]

   To evaluate the safety and tolerability in patients with NLRC4-GOF

2. Confirmation of serological markers of MAS825 [Until End of Study]

   Evaluate the serological markers of MAS825

3. PGA and inflammatory markers at Day 29, end of Period 1 and 2 [Day 29, end of Period 1, end of Period 2]

   Evaluate efficacy of MAS825 to improve clinical status of NLRC4-GOF patients

4. Serological remission via inflammatory markers [Day 29, end of Period 1, and end of Period 2]

   Evaluate efficacy of MAS825 to achieve serological remission

5. Glucocorticoid therapy <0.2mg/kg by end of period 1 [End of Period 1]

   Evaluate the effect of MAS825 on concomitant glucocorticoid administration

6. Time to first flare during period 2 [Period 2]

   Evaluate effect of MAS825 on the time to first flare in patients with NLRC4-GOF

7. Physician Severity Assessment of Disease Signs and Symptoms scale [Screening through EOS]

   Evaluate the efficacy of MAS825 to improve signs and symptoms of NLRC4-GOF

8. Patient' / Parent's global assessment of disease activity (PPGA) scale [Screening through EOS]

   Evaluate effect of MAS825 on patient reported outcomes in patients with NLRC4-GOF over time

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

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).

3. Patients with genetic diagnosis of NLRC4-GOF

4. Clinical history and investigations consistent with autoinflammation with infantile enterocolitis (AIFEC/NLRC4-GOF)

5. At first treatment, evidence of active disease

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 systemic recurrent and/or evidence of active bacterial, fungal, parasitic or viral infections.

• 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.

1. Any conditions or significant medical problems, which in the opinion of the investigator places the patient at unacceptable risk for MAS825 therapy

2. 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.

3. A positive HIV test result at Screening. Evidence of prior testing within 3 months is sufficient.A positive HIV test result at Screening. Evidence of prior testing within 3 months is sufficient.

4. A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result. Evidence of prior testing within 3 months is sufficient.

5. Presence of tuberculosis infection as defined by a positive TB test at Screening. Evidence of prior testing within 3 months is sufficient.

6. Live vaccinations within 1 month prior to MAS825 treatment, during the trial, and up to 3 months following the last dose.

7. Female patients of child-bearing potential (or Tanner stage 2 or above) who are or might become sexually active, 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Cincinnati	Ohio	United States	45229
2	Novartis Investigative Site	Philadelphia	Pennsylvania	United States	19104-4399
3	Novartis Investigative Site	Seattle	Washington	United States	98105
4	Novartis Investigative Site	Praha	CZ	Czechia	121 00
5	Novartis Investigative Site	Bordeaux Cedex		France	33076
6	Novartis Investigative Site	Bron Cedex		France	69677
7	Novartis Investigative Site	Paris cedex 15		France	75015
8	Novartis Investigative Site	Paris		France	75020
9	Novartis Investigative Site	Roma	RM	Italy	00165
10	Novartis Investigative Site	Obu	Aichi	Japan	474 8710
11	Novartis Investigative Site	Barcelona	Catalunya	Spain	08036
12	Novartis Investigative Site	Caceres	Extremadura	Spain	10003
13	Novartis Investigative Site	Istanbul	TUR	Turkey	34098
14	Novartis Investigative Site	Ankara		Turkey	06100
15	Novartis Investigative Site	Istanbul		Turkey	34766

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04641442
• Other Study ID Numbers: CMAS825D12201
• First Posted: Nov 23, 2020
• Last Update Posted: Jul 22, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: NLRC4-GOF, AIFEC, enterocolitis, autoinflammation, MAS, NLRC4 (SCAN4)
• Additional relevant MeSH terms: Enterocolitis

Study Results

No Results Posted as of Jul 22, 2022