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)
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|ClinicalTrials.gov Identifier: NCT03311854|
Recruitment Status : Completed
First Posted : October 17, 2017
Results First Posted : January 26, 2022
Last Update Posted : May 17, 2022
|Condition or disease||Intervention/treatment||Phase|
|Macrophage Activation Syndrome Lymphohistiocytosis, Hemophagocytic Arthritis, Juvenile Adult Onset Still Disease||Drug: Emapalumab||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||14 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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)|
|Actual Study Start Date :||February 20, 2018|
|Actual Primary Completion Date :||May 19, 2020|
|Actual Study Completion Date :||May 19, 2020|
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 Name: Gamifant
- Incidence, Severity, Causality, and Outcomes of AEs (Serious and Nonserious) [ Time Frame: 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:
- Lactate dehydrogenase (LDH)
- Alanine aminotransferase (ALT)
- Aspartate aminotransferase (AST)
- C-reactive protein
- Activated partial thromboplastin time (aPTT)
- Prothrombin time
- Number of Participants Withdrawn Due to Safety Reasons [ Time Frame: Up to Week 8 ]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)
Normalization of laboratory parameters relevant to MAS, as follows:
- WBC count and platelet count above the LLN.
- LDH below 1.5 × the ULN.
- ALT and AST both below 1.5 × the ULN.
- Fibrinogen higher than 100 mg/dL.
- Ferritin levels decreased by at least 80 % from values at screening or baseline (whichever was higher) or below 2000 ng/mL, whichever was lower.
- Time to First MAS Remission [ Time Frame: 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).
- 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.
- Survival Time [ Time Frame: Up to Week 8 ]Number of participants alive at the end of the study
- 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
- 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.
- Pharmacodynamic Parameters [ Time Frame: Up to Week 8 ]Levels of total INF-gamma, CXCL9 and CXCL10
- 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).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03311854
|United States, Ohio|
|Cincinnati Children'S Hospital|
|Cincinnati, Ohio, United States, 45229|
|Hôpital Necker-Enfants Malades, Unité d'Immunologie-hématologie et Rhumatologie pédiatriques|
|Paris, France, 75743|
|IRCCS Ospedale Pediatrico, Bambino Gesù|
|Rome, Italy, 00165|
|Hospital Sant Joan de Deu|
|Barcelona, Spain, 08950|
|Great Ormond Street Hospital for Children|
|London, United Kingdom, WC1N 3JH|