Clinical Trials Register

Summary
EudraCT Number:	2020-003596-17
Sponsor's Protocol Code Number:	CMAS825D12201
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2021-01-27
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Czechia - SUKL

A.2

EudraCT number

2020-003596-17

A.3

Full title of the trial

A three-period multicenter study, with a randomized-withdrawal, double-blinded, 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.

Multicentrické, dvojitě zaslepené a placebem kontrolované klinické hodnocení zahrnující tři období s randomizovaným přerušením léčby ke stanovení účinnosti, bezpečnosti a snášenlivosti MAS825 u pacientů s monogenními IL-18 řízenými autoinflamatorními nemocemi včetně NLRC4-GOF, XIAP deficience nebo mutací CDC42

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

A.4.1

Sponsor's protocol code number

CMAS825D12201

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT04641442

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Novartis Pharma AG
B.1.3.4	Country	Switzerland
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Novartis Pharma AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis s.r.o.
B.5.2	Functional name of contact point	Informační služba - klin. hodnocení
B.5.3	Address:
B.5.3.1	Street Address	Na Pankráci 1724/129
B.5.3.2	Town/ city	Praha 4
B.5.3.3	Post code	140 00
B.5.3.4	Country	Czechia
B.5.4	Telephone number	+420 2 25775 111
B.5.5	Fax number	+420 2 25775 205
B.5.6	E-mail	dotazy.klinickehodnoceni@novartis.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	MAS825
D.3.2	Product code	MAS825
D.3.4	Pharmaceutical form	Concentrate for solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	n/a
D.3.9.2	Current sponsor code	MAS825
D.3.9.4	EV Substance Code	SUB217990
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection/infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

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.

E.1.1.1

Medical condition in easily understood language

Autoinflammation

E.1.1.2

Therapeutic area

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

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	23.1
E.1.2	Level	PT
E.1.2	Classification code	10084306
E.1.2	Term	Autoinflammation with infantile enterocolitis
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	22.0
E.1.2	Level	PT
E.1.2	Classification code	10078961
E.1.2	Term	Immune-mediated enterocolitis
E.1.2	System Organ Class	10017947 - Gastrointestinal disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	SOC
E.1.2	Classification code	10021428
E.1.2	Term	Immune system disorders
E.1.2	System Organ Class	10021428 - Immune system disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

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

E.2.2

Secondary objectives of the trial

- To evaluate the safety and tolerability of MAS825
- Evaluate the serological markers of MAS825
- Evaluate efficacy of MAS825 to improve clinical status of patients
- Evaluate efficacy of MAS825 to achieve serological remission
- Evaluate the effect of MAS825 on concomitant glucocorticoid administration
- Evaluate effect of MAS825 on the time to first flare
- Evaluate the efficacy of MAS825 to improve signs and symptoms
- Evaluate effect of MAS825 on patient reported outcomes in patients over time

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

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

E.4

Principal 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, excluding chronic Epstein-Barr Virus (EBV).
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 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.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. 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.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.Patients weighing >160 kg at Screening.
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.

E.5 End points

E.5.1

Primary end point(s)

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

E.5.1.1

Timepoint(s) of evaluation of this end point

Period 2

E.5.2

Secondary end point(s)

- Number and severity of safety assessments and adverse events
- Confirmation of serological markers of MAS825
- PGA and inflammatory markers at Day 29, end of Period 1 and 2
- Serological remission via inflammatory markers
- Glucocorticoid therapy <0.2mg/kg by end of period 1
- Time to first flare during period 2
- Physician Severity Assessment of Disease Signs and Symptoms scale
- Patient' / Parent's global assessment of disease activity (PPGA) scale

E.5.2.1

Timepoint(s) of evaluation of this end point

Multiple time points up to End of Study visit

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Tolerability, immunogenicity

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Sequential; randomized withdrawal

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Canada

Japan

United States

Czechia

France

Italy

Spain

Türkiye

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

Yes

F.1.1.2.1

Number of subjects for this age range:

F.1.1.3

Newborns (0-27 days)

Yes

F.1.1.3.1

Number of subjects for this age range:

F.1.1.4

Infants and toddlers (28 days-23 months)

Yes

F.1.1.4.1

Number of subjects for this age range:

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Please see Protocol Section 6.1.4

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-05-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-02-18

P. End of Trial
P.	End of Trial Status	Ongoing

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