Study to evaluate the efficacy and safety of MAS825 in patients with autoinflammatory diseases.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

29 Apr 2021 → ongoing

Decision date (initial)

2024-06-10

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Novartis Pharma AG

External identifiers

EU CT number

2023-504419-34-00

EudraCT number

2020-003596-17

ClinicalTrials.gov

NCT04641442

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacodynamic, Pharmacogenetic, Others, Efficacy, Safety, Therapy

To determine the efficacy of MAS825 in prevention of flares in patients with autoinflammatory diseases, including NLRC4-GOF, XIAP deficiency, or CDC42 mutations.

Secondary objectives 8

1. To evaluate the safety and tolerability of MAS825
2. Evaluate the serological markers of MAS825
3. Evaluate efficacy of MAS825 to improve clinical status of patients
4. Evaluate efficacy of MAS825 to achieve serological remission
5. Evaluate the effect of MAS825 on concomitant glucocorticoid administration
6. Evaluate effect of MAS825 on the time to first flare
7. Evaluate the efficacy of MAS825 to improve signs and symptoms
8. Evaluate effect of MAS825 on patient reported outcomes in patients over time

Conditions and MedDRA coding

Autoinflammatory diseases including NLRC4-Gain of Function (GOF) also known as AIFEC (autoinflammation with infantile enterocolitis), X-linked Inhibitor of Apoptosis Protein (XIAP) deficiency, or Cell division control protein 42 homolog (CDC42) mutation.

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, Spanish Agency For Medicines And Health Products

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. All cohorts: 1.Male and female patients weighing at least 3 kg
2. All cohorts: 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 or her legal/authorized representative (if allowed according to local requirements).
3. Cohort 1: 3.Patients with a genetic diagnosis of either NLRC4-GOF, XIAP deficiency, or CDC42 mutation.
4. Cohort 1: 4.Clinical history and investigations consistent with autoinflammation with infantile enterocolitis (AIFEC/NLRC4-GOF), XIAP or CDC42.
5. Cohort 1: 5.At first treatment, evidence of active disease
6. Cohort 2: 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.

Exclusion criteria 11

1. 1.History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes or to any of the excipients.
2. 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, excluding chronic Epstein-Barr Virus (EBV).
3. 3.Any conditions or significant medical problems, which in the opinion of the investigator places the patient at unacceptable risk for MAS825 therapy
4. 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 prior to MAS825 treatment with the exceptions of: - glucocorticoids - cyclosporin - targeted binding or blocking therapies, which must be discontinued prior to treatment with MAS825 - drugs listed as prohibited medication in the protocol, for which the washout periods should be followed as outlined in the protocol.
5. 5.A positive HIV test result at Screening. Evidence of prior testing within 3 months is sufficient.
6. 6.A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result. Evidence of prior testing within 3 months is sufficient.
7. 7.Presence of tuberculosis infection as defined by a positive TB test at Screening. Evidence of prior testing within 3 months is sufficient.
8. 8.Live vaccinations within 1 month prior to MAS825 treatment, during the trial, and up to 3 months following the last dose.
9. 9.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.
10. 10.Patients weighing >160 kg at Screening.
11. 11. For CDC42 mutation patients: Takenouchi-Kosaki syndrome – CDC42 mutations associated with a diverse syndrome characterized by variable development delays, cardiac, brain and hematological abnormalities.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

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

Secondary endpoints 7

1. - Confirmation of serological markers of MAS825
2. - PGA and inflammatory markers at Day 29, end of Period 1 and Period 2
3. - Serological remission via inflammatory markers
4. - Glucocorticoid therapy ≤0.2mg/kg/day by end of period 1
5. - Time to first flare during period 2
6. - Physician Severity Assessment of Disease Signs and Symptoms scale
7. - Patient' / Parent's global assessment of disease activity (PPGA) scale

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel Town

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 21

Locations

4 EU/EEA countries · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 55 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications