- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03311854
A Study to Investigate the Safety and Efficacy of Emapalumab, an Anti-IFN-gamma mAb in Patients With Systemic Juvenile Idiopathic Arthritis (sJIA) or Adult-onset Still's Disease (AOSD) Developing Macrophage Activation Syndrome/Secondary HLH (MAS/sHLH)
May 16, 2022 updated by: Swedish Orphan Biovitrum
A Pilot, Open-label, Single Arm, Multicenter Study to Evaluate Safety, Tolerability, Pharmacokinetics and Efficacy of Intravenous Administrations of Emapalumab, an Anti-interferon Gamma (Anti-IFNγ) Monoclonal Antibody, in Patients With Systemic Juvenile Idiopathic Arthritis (sJIA) or Adult-onset Still's Disease (AOSD) Developing Macrophage Activation Syndrome/Secondary HLH (MAS/sHLH)
Macrophage Activation Syndrome (MAS) is a rare, life-threatening condition characterized by uncontrolled hyperinflammation which may develop on the background of systemic Juvenile Idiopathic Arthritis (sJIA) or Adult-onset Still's Disease (AOSD).
Emapalumab is a monoclonal antibody neutralizing interferon-gamma (IFN-gamma), a key cytokine which contributes to the inflammation and tissue damage seen in MAS.
The purpose of this study is to assess the safety, tolerability and efficacy of emapalumab in sJIA or AOSD participants developing MAS, presenting an inadequate response to high dose glucocorticoid treatment.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
14
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Paris, France, 75743
- Hôpital Necker-Enfants Malades, Unité d'Immunologie-hématologie et Rhumatologie pédiatriques
-
-
-
-
-
Rome, Italy, 00165
- IRCCS Ospedale Pediatrico, Bambino Gesù
-
-
-
-
-
Barcelona, Spain, 08950
- Hospital Sant Joan de Déu
-
-
-
-
-
London, United Kingdom, WC1N 3JH
- Great Ormond Street Hospital for Children
-
-
-
-
Ohio
-
Cincinnati, Ohio, United States, 45229
- Cincinnati CHildren's Hospital
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
1 second and older (Child, Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Patients of both genders
- For sJIA patients: Confirmed sJIA diagnosis. For patients presenting with MAS in the context of the onset of sJIA, high presumption of sJIA will suffice for eligibility. For AOSD patients: confirmed AOSD diagnosis as per Yamaguchi criteria.
- Diagnosis of active MAS.
- An inadequate response to high dose i.v. glucocorticoid treatment administered for at least 3 days as per local standard of care (including but not limited to pulses of 30 mg/kg PDN on 3 consecutive days). High dose i.v. glucocorticoid should not be lower than 2 mg/kg/day of PDN equivalent in 2 divided doses (or at least 60 mg/day in patients of 30 kg or more). In case of rapid worsening of the patient's condition and/or lab parameters, inclusion may occur within less than 3 days from starting high dose i.v. glucocorticoids.
- Tocilizumab, TNF inhibitors and canakinumab, if administered, have to be discontinued before emapalumab initiation.
- Having received guidance on contraception for both male and female patients sexually active and having reached puberty. Females of child-bearing potential require use of highly effective contraceptive measures. Males with partners(s) of child-bearing potential must agree to take appropriate precautions.
- Informed consent provided by the patient (as required by local law), or by the patient's legally authorized representative(s) with the assent of patients who are legally capable of providing it, as applicable.
Exclusion Criteria:
- Diagnosis of suspected or confirmed primary HLH or HLH consequent to a neoplastic disease.
- Active mycobacteria (typical and atypical), Histoplasma Capsulatum, Shigella, Salmonella, Campylobacter and Leishmania infections.
- Clinical suspicion of latent tuberculosis.
- Positive serology for HIV antibodies.
- Presence of malignancy.
- Patients who have another concomitant disease or malformation severely affecting the cardiovascular, pulmonary, CNS, liver or renal function that in the opinion of the Investigator may significantly affect likelihood to respond to treatment and/or assessment of emapalumab safety.
- History of hypersensitivity or allergy to any component of the study drug
- Receipt of a BCG vaccine within 12 weeks prior to screening.
- Receipt of live or attenuated live vaccines (other than BCG) within 6 weeks prior to screening.
- Pregnant or lactating female patients.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Emapalumab
|
Emapalumab was administered at an initial dose of 6 mg/kg by intravenous infusion.
Emapalumab treatment continued at a dose of 3 mg/kg, every 3 days until study day 15, and then twice-a-week for an additional 2 weeks, i.e., until study day 28.
The emapalumab regimen could be adapted (the frequency between infusions shortened, the dose increased, or the treatment prolonged beyond 4 weeks) upon assessment of a favourable benefit-risk profile.
There was a 4-week off-drug follow-up period (up to Week 8).
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence, Severity, Causality, and Outcomes of AEs (Serious and Nonserious)
Time Frame: Up to Week 8
|
Up to Week 8
|
|
Evolution of Laboratory Parameters
Time Frame: Up to Week 8
|
Shifts from baseline in the following MAS-relevant laboratory parameters are reported:
|
Up to Week 8
|
Number of Participants Withdrawn Due to Safety Reasons
Time Frame: Up to Week 8
|
Up to Week 8
|
|
Number of Participants Achieving MAS Remission at Week 8 After Initiation of Emapalumab Treatment
Time Frame: Week 8
|
Remission from MAS was evaluated according to the following criteria: Resolution of clinical signs and symptoms according to the investigator (MAS clinical signs and symptoms activity score ≤ 1) and Normalization of laboratory parameters relevant to MAS, as follows:
|
Week 8
|
Time to First MAS Remission
Time Frame: Up to Week 8
|
Up to Week 8
|
|
Number of Participants for Whom Glucocorticoids Could be Permanently Tapered at Any Time During the Study
Time Frame: Up to Week 8
|
Permanently tapering by at least 50% of the equivalent dose of prednisone.
This was defined as achieving reduction of 50% of the baseline dose [SD0] and maintaining the reduction until the end of study).
|
Up to Week 8
|
Time to Achievement of Permanent Glucocorticoids Tapering
Time Frame: Up to Week 8
|
Time to achievement of permanent glucocorticoid tapering by at least 50% of the equivalent dose of prednisone administered at emapalumab treatment start.
|
Up to Week 8
|
Survival Time
Time Frame: Up to Week 8
|
Number of participants alive at the end of the study
|
Up to Week 8
|
Number of Participants Withdrawn From the Study Due to Lack of Efficacy
Time Frame: Up to Week 8
|
Number of participants withdrawn from the study due to lack of efficacy
|
Up to Week 8
|
Levels of Emapalumab Concentration
Time Frame: Data from the following time points are presented: SD0 (pre- and post-dose), Week 4 Visit 2 (pre- and post-dose), and 4-week follow-up visit/EoS.
|
On all infusion days, PK samples were collected before the infusion start and between 15 and 30 minutes after infusion completion.
In addition, following the first emapalumab infusion, PK samples were collected approximately 24 and 48 hours post-infusion, and following the second emapalumab infusion, PK samples were collected approximately 48 hours post-infusion.
Upon treatment completion, PK samples were collected on all non-infusion visits until the 4-week follow-up visit/EOS.
|
Data from the following time points are presented: SD0 (pre- and post-dose), Week 4 Visit 2 (pre- and post-dose), and 4-week follow-up visit/EoS.
|
Pharmacodynamic Parameters
Time Frame: Up to Week 8
|
Levels of total INF-gamma, CXCL9 and CXCL10
|
Up to Week 8
|
Number of Participants Who Demonstrated a Presence of Circulating Antibodies Against Emapalumab to Determine Immunogenicity
Time Frame: Up to Week 8
|
The presence of circulating antibodies against emapalumab was inferred by positive results for anti-drug antibodies (ADAs).
|
Up to Week 8
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
February 20, 2018
Primary Completion (Actual)
May 19, 2020
Study Completion (Actual)
May 19, 2020
Study Registration Dates
First Submitted
August 21, 2017
First Submitted That Met QC Criteria
October 11, 2017
First Posted (Actual)
October 17, 2017
Study Record Updates
Last Update Posted (Actual)
May 17, 2022
Last Update Submitted That Met QC Criteria
May 16, 2022
Last Verified
May 1, 2022
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Autoimmune Diseases
- Disease
- Joint Diseases
- Musculoskeletal Diseases
- Rheumatic Diseases
- Connective Tissue Diseases
- Arthritis, Rheumatoid
- Histiocytosis, Non-Langerhans-Cell
- Histiocytosis
- Syndrome
- Arthritis
- Arthritis, Juvenile
- Still's Disease, Adult-Onset
- Lymphohistiocytosis, Hemophagocytic
- Macrophage Activation Syndrome
Other Study ID Numbers
- NI-0501-06
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Arthritis, Juvenile
-
University of AarhusAarhus University HospitalCompletedPolyarticular Juvenile Rheumatoid Arthritis | Systemic Juvenile Idiopathic Arthritis | Juvenile Idiopathic Arthritis, OligoarthritisDenmark
-
University of Sao Paulo General HospitalNot yet recruitingJuvenile Idiopathic Arthritis | Juvenile Rheumatoid Arthritis | Juvenile ArthritisBrazil
-
Institut National de la Santé Et de la Recherche...CompletedSystemic-Onset Juvenile Idiopathic ArthritisFrance
-
NovartisCompletedArthritis, Juvenile RheumatoidItaly
-
Novartis PharmaceuticalsCompletedSystemic Juvenile Idiopathic Arthritis (SJIA)Italy, Russian Federation, Turkey, Belgium, Spain, Germany, France, Israel, Canada, United States, Hungary, Austria, Brazil, Sweden, Netherlands, Poland
-
Tufts Medical CenterHoffmann-La RocheTerminatedArthritis, Juvenile Rheumatoid | Still's Disease, Juvenile OnsetUnited States
-
University of British ColumbiaUniversity of Manitoba; The Hospital for Sick Children; McGill University Health... and other collaboratorsRecruiting
-
AbbVieCompletedPolyarticular Juvenile Idiopathic Arthritis
-
GeneScience Pharmaceuticals Co., Ltd.Not yet recruitingActive Systemic Juvenile Idiopathic ArthritisChina
-
Assistance Publique - Hôpitaux de ParisRecruitingJuvenile Idiopathic Arthritis (JIA)France
Clinical Trials on Emapalumab
-
Swedish Orphan BiovitrumRecruitingSystemic Lupus Erythematosus | Macrophage Activation Syndrome | Still Disease | Secondary Hemophagocytic Lymphohistiocytosis | SJIA | AOSD | MASUnited States, Belgium, Italy, Netherlands, United Kingdom, China, France, Spain, Czechia, Canada, Sweden, Japan, Germany, Poland
-
M.D. Anderson Cancer CenterSobi, Inc.Not yet recruiting
-
Swedish Orphan BiovitrumCompletedStudy to Assess the Efficacy and Safety of Emapalumab in Primary Haemophagocytic LymphohistiocytosisPrimary Hemophagocytic LymphohistiocytosisSpain, United States, United Kingdom, Germany, Italy, Sweden, Canada, Switzerland
-
Swedish Orphan BiovitrumActive, not recruitingPrimary Hemophagocytic LymphohistiocytosisChina
-
Swedish Orphan BiovitrumSeventh Framework ProgrammeCompletedHemophagocytic LymphohistiocytosisUnited States, France, Italy, Spain, United Kingdom
-
Swedish Orphan BiovitrumLight Chain Bioscience - Novimmune SATerminatedHemophagocytic LymphohistiocytosesUnited States
-
Swedish Orphan BiovitrumPRA Health Sciences; Cromsource; BioMérieux; Q2 Solutions; Cytel Inc.; ABF Pharmaceutical...Terminated
-
Instituto Bioclon S.A. de C.V.University of ArizonaCompletedBlood Coagulation Disorders | Snake BiteUnited States
-
Swedish Orphan BiovitrumTerminated
-
Memorial Sloan Kettering Cancer CenterSobi, Inc.RecruitingImmune System Diseases | Autoimmune Lymphoproliferative | Primary Immune Regulatory DisorderUnited States