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)

• Register: ClinicalTrials.gov
• Last refreshed on: 30 May 2022
• Main ID: NCT03311854
• Date of registration: 21/08/2017
• Prospective Registration: Yes
• Primary sponsor: Swedish Orphan Biovitrum
• Public title: 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)
• Scientific 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-IFN?) 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)
• Date of first enrolment: February 20, 2018
• Target sample size: 14
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03311854
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

France, Italy, Netherlands, Spain, United Kingdom, United States

Key inclusion & exclusion criteria

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.



Age minimum: N/A
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Arthritis, Juvenile

Lymphohistiocytosis, Hemophagocytic

Adult Onset Still Disease

Macrophage Activation Syndrome

Intervention(s)

Drug: Emapalumab

Primary Outcome(s)

Number of Participants Withdrawn Due to Safety Reasons [Time Frame: Up to Week 8]

Number of Participants Withdrawn From the Study Due to Lack of Efficacy [Time Frame: Up to Week 8]

Pharmacodynamic Parameters [Time Frame: Up to Week 8]

Number of Participants Achieving MAS Remission at Week 8 After Initiation of Emapalumab Treatment [Time Frame: Week 8]

Evolution of Laboratory Parameters [Time Frame: Up to Week 8]

Incidence, Severity, Causality, and Outcomes of AEs (Serious and Nonserious) [Time Frame: 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.]

Number of Participants for Whom Glucocorticoids Could be Permanently Tapered at Any Time During the Study [Time Frame: 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]

Time to First MAS Remission [Time Frame: Up to Week 8]

Survival Time [Time Frame: Up to Week 8]

Time to Achievement of Permanent Glucocorticoids Tapering [Time Frame: Up to Week 8]

Secondary ID(s)

NI-0501-06

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 26/01/2022
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03311854