Evaluate Efficacy, Safety and Tolerability, PK and PD of Emapalumab in Children and Adults With MAS in Still's or SLE

NCT ID: NCT05001737

Last Updated: 2025-06-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-12-15
• Study Completion Date: 2025-06-04

Brief Summary

The purpose of this study is to assess the safety, tolerability and efficacy of emapalumab in children and adults with macrophage activation syndrome (sHLH/MAS) in Still's disease (including systemic juvenile idiopathic arthritis and adult onset Still's disease) or with sHLH/MAS in systemic lupus erythematous, resenting an inadequate response to high dose glucocorticoid treatment.

Detailed Description

Study NI-0501-14 is a two-cohort trial that enrolls subjects who are diagnosed with sHLH/MAS (MAS being a form of secondary HLH) and who are presenting an inadequate response to high doses of GCs. These subjects will be enrolled in 2 cohorts as per their background disease. The cohorts are defined as follows:

• Cohort 1: MAS in the context of sJIA and AOSD.
• Cohort 2: MAS in the context of pediatric and adult SLE.

The study has the objectives to investigate the efficacy, safety and tolerability, for 8 weeks, and PK and PD, QoL and immunogenicity in these 2 cohorts for up to 1 year after last dose of of emapalumab.

Macrophage Activation Syndrome (MAS) Secondary Hemophagocytic Lymphohistiocytosis (sHLH) systemic Juvenile Idiopathic Arthritis (sJIA) Adult-onset Still's Disease (AOSD) Systemic Lupus Erythematosus (SLE)

Conditions

Macrophage Activation Syndrome; Secondary Hemophagocytic Lymphohistiocytosis; Still Disease; Systemic Lupus Erythematosus; SJIA; AOSD; MAS

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1 (sJIA and AOSD) and Cohort 2 (SLE)

MAS in the context of systemic juvenile idiopathic arthritis and adult onset Still's disease (sJIA and AOSD) or SLE

Group Type: EXPERIMENTAL

Emapalumab

Intervention Type: DRUG

Emapalumab iv infusion

Interventions

Emapalumab

Emapalumab iv infusion

Intervention Type: DRUG

Other Intervention Names

NI-0501; emapalumab-lzsg; ATC code: L04AA39 (WHO)

Eligibility Criteria

Inclusion Criteria

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.

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 PDN 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 subjects of child-bearing potential willing to use highly effective methods of contraception from study drug initiation to 6 months after the last dose of study drug.

6. Cohort 1:

1. Confirmed sJIA diagnosis. For subjects presenting with MAS in the context of the onset of sJIA, high presumption of sJIA will suffice for eligibility.

2. Confirmed diagnosis of AOSD as per Yamaguchi criteria.

7. Cohort 2:

1. Confirmed diagnosis of SLE as per SLICC'12 criteria.

Exclusion Criteria

1. Primary 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 mononuclear 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. Subjects treated with etoposide for MAS in the last 1 month.

6. Clinically active mycobacteria (typical and atypical), Histoplasma Capsulatum, or Salmonella infections.

7. Evidence of leishmania infections.

8. Evidence of latent tuberculosis.

9. History of hypersensitivity or allergy to any component of the study drug.

10. Receipt of a Bacillus Calmette-Guerin (BCG) vaccine within 12 weeks prior to screening.

11. Receipt of a live or attenuated live (other than BCG) vaccine within 4 weeks prior to screening.

12. Pregnancy or lactating female subjects.

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Swedish Orphan Biovitrum

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Brian Jamieson, MD

Role: STUDY_DIRECTOR

Swedish Orphan Biovitrum

Locations

UAB Hospital

Birmingham, Alabama, United States

UCLA Health

Los Angeles, California, United States

University of Florida

Gainesville, Florida, United States

Children's Healthcare of Atlanta

Atlanta, Georgia, United States

University of Minnesota Masonic Children's Hospital

Minneapolis, Minnesota, United States

Akron Children's Hospital

Akron, Ohio, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Nationwide Children's Hospital, Abigail Wexner Research Institute

Columbus, Ohio, United States

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Universitair Ziekenhuis Leuven

Leuven, , Belgium

Alberta Children's Hospital

Calgary, , Canada

University of Calgary

Calgary, , Canada

Centre Hospitalier de l'Université de Montréal

Montreal, , Canada

Centre Hospitalier Universitaire Sainte-Justine

Montreal, , Canada

Hospital for sick children

Toronto, , Canada

Beijing Children's Hospital

Beijing, , China

Beijing Friendship Hospital

Beijing, , China

Children's Hospital of Fudan University

Shanghai, , China

Fakultní nemocnice Olomouc

Olomouc, , Czechia

Vseobecna Fakultni Nemocnice v Praze

Prague, , Czechia

Hôpital Claude Huriez

Lille, , France

Hôpital De La Conception

Marseille, , France

Hôpital Necker-Enfants Malades

Paris, , France

Hôpital Universitaire Pitié Salpêtrière

Paris, , France

Charité Universitätsmedizin

Berlin, , Germany

Universitätsklinikum Heidelberg

Heidelberg, , Germany

IRCCS G. Gaslini

Genova, , Italy

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, , Italy

Ospedale Pediatrico Bambino Gesù

Roma, , Italy

IRCCS - Materno-Infantile Burlo Garofolo

Trieste, , Italy

St. Marianna University School of Medicine Hospital

Kawasaki, , Japan

Osaka Medical and Pharmaceutical University Hospital

Takatsuki, , Japan

Tokyo Medical and Dental University Hospital

Tokyo, , Japan

Yokohama City University Hospital

Yokohama, , Japan

UMC Utrecht

Utrecht, , Netherlands

Szpital Specjalistyczny im. J. Dietla w Krakowie

Krakow, , Poland

Wojewódzki Specjalistyczny Szpital Dziecięcy im. św. Ludwika w Krakowie

Krakow, , Poland

Ortopedyczno - Rehabilitacyjny Szpital Kliniczny im. Wiktora Degi Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu

Poznan, , Poland

Hospital Sant Joan de Déu

Barcelona, , Spain

Hospital Universitario La Paz

La Paz, , Spain

Hospital Universitario

La Paz, , Spain

Hospital Universitari i Politècnic La Fe

Valencia, , Spain

Great Ormond Street Hospital

London, , United Kingdom

Imperial College Healthcare NHS Trust

London, , United Kingdom

Countries

United States; Belgium; Canada; China; Czechia; France; Germany; Italy; Japan; Netherlands; Poland; Spain; United Kingdom

Other Identifiers

2021-001577-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NI-0501-14

Identifier Type: -

Identifier Source: org_study_id