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

NCT05001737 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: NI-0501-142021-001577-24
• Study Type: interventional
• Target: 33
• Locations: 13 countries
• Sites: 44

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Proportion of Subjects With Complete Response (CR) at Week 8 After First Administration of Emapalumab

  Resolution of clinical signs and symptoms present at baseline: The macrophage activation syndrome (MAS) clinical activity will be measured on a visual analog scale (VAS) 10 cm. Resolution of clinical signs and symptoms present at baseline: The MAS clinical activity will be measured on a visual analog scale (VAS) 10 cm. Clinical signs will be considered as resolved if VAS is below or equal to 1/10. And Normalization of laboratory parameters relevant to MAS, as follows: WBC above LLN, platelet count above LLN, LDH below 1.5 ULN, ALT below 1.5 ULN, AST below 1.5 ULN, fibrinogen higher than 100 mg/dL, ferritin levels decreased by at least 80 % from values at screening or baseline (whichever is higher) or below 2000 ng/ml, whichever is lower

  8 weeks

Secondary Outcomes (9)

• Number of Patients With Glucocorticoids (GC)s 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 Whichever Occurs First

  At any time within the first 8 weeks from start of emapalumab treatment

• Number of Patients With GCs Tapering to ≤1mg/kg/Day of PDN Equivalent at Any Time Until End of Study (EOS).

  At any time in the study, up to 1 year

• Time to Achieve GCs Tapering

  At any time in the study, up to 1 year

• Time to First Complete Response (CR)

  At any time in the study, up to 1 year

• Proportion of Subjects With Overall Response as Defined by CR or Partial Response (PR)

  At week 8

Other Outcomes (10)

• Adverse Events (AEs) (Serious and Non-serious).

  At any time in the study, up to 1 year

• Study Interruption Due to Safety Reasons

  At any time in the study, up to 1 year

• Laboratory Parameters

  At any time in the study, up to 1 year

Study Arms (1)

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

EXPERIMENTAL

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

Drug: Emapalumab

Interventions

Emapalumab DRUG

Emapalumab iv infusion

Also known as: NI-0501, emapalumab-lzsg, ATC code: L04AA39 (WHO)

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

Eligibility Criteria

• Age: 6 Months - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Male and female subjects aged between 6 months and 80 years of age at the time of diagnosis of MAS.
• MAS defined as per the criteria defined below for each cohort and requiring treatment with GCs.
• Interventional phase in all cohorts
• 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.
• Male and female subjects aged between 6 months and 80 years of age at the time of diagnosis of active MAS.
• 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
• 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.
• Cohort 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.
• Confirmed diagnosis of AOSD as per Yamaguchi criteria.
• Cohort 2:
• Confirmed diagnosis of SLE as per SLICC'12 criteria.

You may not qualify if:

• 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.
• 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.
• Treatment with canakinumab, JAK inhibitors, TNF inhibitors and tocilizumab at the time of emapalumab initiation.
• Ongoing treatment with anakinra at a dose above 4 mg/kg at time of emapalumab initiation.
• Subjects treated with etoposide for MAS in the last 1 month.
• Clinically active mycobacteria (typical and atypical), Histoplasma Capsulatum, or Salmonella infections.
• Evidence of leishmania infections.
• Evidence of latent tuberculosis.
• History of hypersensitivity or allergy to any component of the study drug.
• Receipt of a Bacillus Calmette-Guerin (BCG) vaccine within 12 weeks prior to screening.
• Receipt of a live or attenuated live (other than BCG) vaccine within 4 weeks prior to screening.
• Pregnancy or lactating female subjects.

Sponsors & Collaborators

• Swedish Orphan Biovitrum: lead

Study Sites (44)

UAB Hospital

Birmingham, Alabama, 35233, United States

Location

UCLA Health

Los Angeles, California, 90095, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30329, United States

Location

University of Minnesota Masonic Children's Hospital

Minneapolis, Minnesota, 55455, United States

Location

Akron Children's Hospital

Akron, Ohio, 44308, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Nationwide Children's Hospital, Abigail Wexner Research Institute

Columbus, Ohio, 43205, United States

Location

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Universitair Ziekenhuis Leuven

Leuven, Belgium

Location

Alberta Children's Hospital

Calgary, Canada

Location

University of Calgary

Calgary, Canada

Location

Centre Hospitalier de l'Université de Montréal

Montreal, Canada

Location

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Canada

Location

Hospital for sick children

Toronto, Canada

Location

Beijing Children's Hospital

Beijing, China

Location

Beijing Friendship Hospital

Beijing, China

Location

Children's Hospital of Fudan University

Shanghai, China

Location

Fakultní nemocnice Olomouc

Olomouc, Czechia

Location

Vseobecna Fakultni Nemocnice v Praze

Prague, Czechia

Location

Hôpital Claude Huriez

Lille, France

Location

Hôpital De La Conception

Marseille, France

Location

Hôpital Necker-Enfants Malades

Paris, France

Location

Hôpital Universitaire Pitié Salpêtrière

Paris, France

Location

Charité Universitätsmedizin

Berlin, Germany

Location

Universitätsklinikum Heidelberg

Heidelberg, Germany

Location

IRCCS G. Gaslini

Genova, Italy

Location

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, Italy

Location

Ospedale Pediatrico Bambino Gesù

Roma, Italy

Location

IRCCS - Materno-Infantile Burlo Garofolo

Trieste, Italy

Location

St. Marianna University School of Medicine Hospital

Kawasaki, Japan

Location

Osaka Medical and Pharmaceutical University Hospital

Takatsuki, Japan

Location

Tokyo Medical and Dental University Hospital

Tokyo, Japan

Location

Yokohama City University Hospital

Yokohama, Japan

Location

UMC Utrecht

Utrecht, Netherlands

Location

Szpital Specjalistyczny im. J. Dietla w Krakowie

Krakow, Poland

Location

Wojewódzki Specjalistyczny Szpital Dziecięcy im. św. Ludwika w Krakowie

Krakow, Poland

Location

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

Poznan, Poland

Location

Hospital Sant Joan de Déu

Barcelona, Spain

Location

Hospital Universitario La Paz

La Paz, Spain

Location

Hospital Universitario

La Paz, Spain

Location

Hospital Universitari i Politècnic La Fe

Valencia, Spain

Location

Great Ormond Street Hospital

London, United Kingdom

Location

Imperial College Healthcare NHS Trust

London, United Kingdom

Location

MeSH Terms

Conditions

Macrophage Activation Syndrome; Arthritis, Juvenile; Lupus Erythematosus, Systemic

Interventions

Emapalumab; World Health Organization

Condition Hierarchy (Ancestors)

Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases

Intervention Hierarchy (Ancestors)

United Nations; International Agencies; Organizations; Health Care Economics and Organizations

Limitations and Caveats

Enrollment in Cohort 2 was discontinued by the Sponsor after 8 (of 16 planned) patients were enrolled in June 2024 due to enrollment challenges in this patient population.

Results Point of Contact

• Title: Medical Info
• Organization: Swedish Orphan Biovitrum (Sobi)

medical.info@sobi.com

+1 774 548 5650

Study Officials

• Brian Jamieson, MD

  Swedish Orphan Biovitrum

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Masking Details: Open label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 2 cohorts

Study Record Dates

• First Submitted: June 16, 2021
• First Posted: August 12, 2021
• Study Start: December 15, 2021
• Primary Completion: June 30, 2024
• Study Completion: June 4, 2025
• Last Updated: February 19, 2026
• Results First Posted: February 19, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1); ES (4); US (9); PL (3); FR (4); CN (3); CZ (2); JP (4); GB (2); CA (5); IT (4); NL (1); DE (2)