Clinical Trials Register

Summary
EudraCT Number:	2021-001577-24
Sponsor's Protocol Code Number:	NI-0501-14
National Competent Authority:	Sweden - MPA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-11-22
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

Sweden - MPA

A.2

EudraCT number

2021-001577-24

A.3

Full title of the trial

A two-cohort, open-label, single arm, multicenter study to evaluate efficacy, safety and tolerability, pharmacokinetics and pharmacodynamics, of emapalumab in children and adults with macrophage activation syndrome (MAS) in Still’s disease (including systemic juvenile idiopathic arthritis and Adult onset Still’s disease) or with MAS in Systemic lupus erythematous

A.3.1

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

A study to evaluate efficacy, safety and tolerability, pharmacokinetics and pharmacodynamics, of emapalumab in children and adults with macrophage activation syndrome (MAS)

A.3.2

Name or abbreviated title of the trial where available

NI-0501-14

A.4.1

Sponsor's protocol code number

NI-0501-14

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/109/2020

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Swedish Orphan Biovitrum AG (Sobi 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	Swedish Orphan Biovitrum AG (Sobi 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	Swedish Orphan Biovitrum AG (Sobi AG)
B.5.2	Functional name of contact point	Clinical Development Swedish Orphan
B.5.3	Address:
B.5.3.1	Street Address	Riehenring 182
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4058
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	19193387864
B.5.6	E-mail	brian.jamieson@sobi.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	Yes
D.2.5.1	Orphan drug designation number	EU/3/10/749
D.3 Description of the IMP
D.3.1	Product name	Emapalumab
D.3.2	Product code	NI-0501
D.3.4	Pharmaceutical form	Concentrate for solution for 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	Emapalumab
D.3.9.2	Current sponsor code	NI-0501
D.3.9.4	EV Substance Code	SUB188645
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	5
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.IMP: 2
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	Yes
D.2.5.1	Orphan drug designation number	EU/3/10/749
D.3 Description of the IMP
D.3.1	Product name	Emapalumab
D.3.2	Product code	NI-0501
D.3.4	Pharmaceutical form	Concentrate for solution for 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	Emapalumab
D.3.9.2	Current sponsor code	NI-0501
D.3.9.4	EV Substance Code	SUB188645
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	25
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Macrophage activation syndrome (MAS) in the context of Systemic juvenile inflammatory arthritis (sJIA) and Adult onset Still’s disease (AOSD).
MAS in the context of pediatric and adult Systemic lupus erythematosus (SLE).

E.1.1.1

Medical condition in easily understood language

Children and adults with macrophage activation syndrome (MAS)

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10071583
E.1.2	Term	Haemophagocytic lymphohistiocytosis
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 demonstrate efficacy of emapalumab in the treatment of patients in:
- Cohort 1: MAS in the context of systemic juvenile idiopathic arthritis and adult onset Still’s disease (AOSD).
- Cohort 2: MAS in the context of pediatric and adult systemic lupus erythematosus (SLE).

E.2.2

Secondary objectives of the trial

 To demonstrate efficacy of emapalumab with respect to tapering of glucocorticoids (GCs).
 To evaluate the time to onset of response to emapalumab treatment.
 To evaluate efficacy of emapalumab with respect to overall response.
 To evaluate the sustained efficacy of emapalumab treatment.
 To evaluate the patient´s survival after treatment of emapalumab.
 To evaluate the safety and tolerability of emapalumab.
 To evaluate subject reported outcome of MAS in patients treated with emapalumab.
 To determine the pharmacokinetic (PK) profile of emapalumab.
 To determine the pharmacodynamic (PD) profile of emapalumab.
 To determine the immunogenicity of emapalumab

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Run-in phase in all cohorts
1. Informed consent provided by the subject or by the subject's legally authorized representative(s) with the assent of subjects who are legally capable of providing it, as required by local law.
2. Male and female subjects aged between 6 months and 80 years of age at the time of diagnosis of MAS.
3. MAS defined as per the criteria defined below for each cohort and requiring treatment with GCs as per standard of care.
Interventional phase in all cohorts
1. Informed consent provided by the subject or by the subject’s legally authorized representative(s) with the assent of subjects who are legally capable of providing it, as as required by local law.
2. Male and female subjects aged between 6 months and 80 years of age at the time of diagnosis of active MAS.
3. Subjects who have shown an inadequate response to high dose intravenous (i.v.) GCs administered for at least 3 days according to local standard clinical practice, including but not limited to pulses of 30 mg/kg methylprednisolone (mPDN)on 3 consecutive days. High i.v. GCs dose is recommended not to be lower than 2 mg/kg/ day PDN equivalent (or at least 60 mg/day in pediatric subjects of 30 kg or more, and at least 1g/day in adult MAS subjects). In case of rapid worsening of the subject’s condition and/or laboratory parameters, as per Investigator judgment, inclusion may occur within less than 3 days from starting high dose GCs.
4. Diagnosis of active MAS confirmed by the treating rheumatologist, having ascertained the followings:
a. Febrile subjects presenting with ferritin > 684 ng/mL.
b. and any 2 of:
i. Platelet count ≤ 181 x109/L
ii. AST-level > 48 U/L
iii. Triglycerides > 156 mg/dL
iv. Fibrinogen level ≤ 360 mg/dL
5. Female patients of child-bearing potential (sexually or non-sexually active). Female patients who are sexually active must be willing to use highly effective methods of contraception from study drug initiation to 6 months after the last dose of study drug.
Specific inclusion criteria to Cohort 1 and Cohort 2
6. Cohort 1:
a. Confirmed sJIA diagnosis. For subjects presenting with MAS in the context of the onset of sJIA, high presumption of sJIA will suffice for eligibility.
b. Confirmed diagnosis of AOSD as per Yamaguchi criteria (Yamaguchi et al. 1992).
7. Cohort 2:
a. Confirmed diagnosis of SLE as per Systemic Lupus International Collaborating Clinics (SLICC) 2012 criteria.

E.4

Principal exclusion criteria

1. Primary hemophagocytic lymphohistiocytosis (p-HLH) documented by either the presence of a known causative genetic mutation or abnormal perforin expression and CD107a degranulation assay as described with primary hemophagocytic lymphohistiocytosis or by the presence of family history.
2. Confirmed malignancy. Note: subjects with a suspected malignancy should have mononuclaear cells typed by flow cytometry and/or tissue biopsy, as applicable, to rule out malignancy.
3. Treatment with canakinumab, JAK inhibitors, TNF inhibitors and tocilizumab at the time of emapalumab initiation.
4. Ongoing treatment with anakinra at a dose above 4 mg/kg at time of emapalumab initiation.
5. Patients treated with etoposide for MAS in the last 1 month.
6. Presence of any medical or psychological condition or laboratory result that in the opinion of the Investigator can interfere with the patient's ability to comply with the protocol requirements or makes the patient not appropriate for inclusion to the study and treatment with emapalumab.
7. Foreseeable inability to cooperate with given instructions or study procedures.
8. Clinically active mycobacteria (typical and atypical), Histoplasma Capsulatum, or Salmonella infections.
9. Evidence of leishmania infections.
10. Evidence of latent tuberculosis.
11. History of hypersensitivity or allergy to any component of the study drug.
12. Receipt of a Bacillus Calmette-Guerin (BCG) vaccine within 12 weeks prior to screening.
13. Receipt of a live or attenuated live (other than BCG) vaccine within 4 weeks prior to screening.
14. Pregnancy or lactating female patients.

E.5 End points

E.5.1

Primary end point(s)

Proportion of subjects with complete response (CR) at Week 8 after first administration of emapalumab.

E.5.1.1

Timepoint(s) of evaluation of this end point

week 8

E.5.2

Secondary end point(s)

 GCs tapering to a dose below 50 % of prednisolone (PDN) equivalent at the time of emapalumab start or to the same (or lower) dose being administered before the occurrence of MAS (in subjects already treated for the underlying condition) whichever occurs first at any time during the study.
 GCs tapering to ≤1mg/kg/day of PDN equivalent at any time during the study.
 Time to achieve GCs tapering as described above .
 Time to first CR.
 Proportion of subjects with overall response as defined by CR or PR (partial response).
 Time to first overall response as defined by CR or PR.
 MAS recurrence at any time after achievement of CR.
 Withdrawal from the study due to lack of response as per Investigator decision.
 Survival time.

E.5.2.1

Timepoint(s) of evaluation of this end point

duration of study

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

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

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)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Information not present in EudraCT

E.8.2.2

Placebo

Information not present in EudraCT

E.8.2.3

Other

Information not present in EudraCT

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

China

Japan

Russian Federation

United Kingdom

United States

Belgium

Czechia

France

Germany

Italy

Netherlands

Poland

Spain

Sweden

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)

F.1.1.3

Newborns (0-27 days)

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)

Yes

F.1.3.1

Number of subjects for this age range:

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

paediatric patients

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)

return to standard of care

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

2022-01-07

Ethics Committee Opinion of the trial application

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

P. End of Trial
P.	End of Trial Status	Completed

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