A study to investigate a new medication, NI-0501, in children with the disease systemic Juvenile Idiopathic Arthritis (sJIA) developing Macrophage Activation Syndrome/secondary Hemophagocytic Lymphohistiocytosis (MAS/sHLH)

• Register: EUCTR
• Last refreshed on: 19 March 2018
• Main ID: EUCTR2016-004223-23-IT
• Date of registration: 25/01/2017
• Prospective Registration: Yes
• Primary sponsor: Novimmune SA
• Public title: A study to investigate a new medication, NI-0501, in children with the disease systemic Juvenile Idiopathic Arthritis (sJIA) developing Macrophage Activation Syndrome/secondary Hemophagocytic Lymphohistiocytosis (MAS/sHLH)
• Scientific title: A pilot, open-label, single arm, multicenter study to evaluate safety, tolerability, pharmacokinetics and efficacy of intravenous administrations of NI-0501, an anti-interferon gamma (anti-IFN?) monoclonal antibody, in patients with systemic Juvenile Idiopathic Arthritis (sJIA) developing Macrophage Activation Syndrome/secondary HLH (MAS/sHLH)
• Date of first enrolment: 14/04/2017
• Target sample size: 5
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-004223-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

France, Germany, Italy, Netherlands, Spain, United Kingdom

Contacts

• Name: Clinical Science
• Affiliation: Novimmune SA

• Name: Clinical Science
• Affiliation: Novimmune SA

Key inclusion & exclusion criteria

Inclusion criteria:
•Patients of both genders, aged <18 years
•Confirmed sJIA or high presumption of sJIA.
•Diagnosis of active MAS confirmed by the treating rheumatologist
•Patient presenting an inadequate response to high dose i.v. glucocorticoid treatment
•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
Are the trial subjects under 18? yes
Number of subjects for this age range: 5
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
•Diagnosis of suspected or confirmed primary HLH or HLH consequent to a neoplastic disease.
•Patients treated with Tocilizumab, Canakinumab or TNF inhibitors within 5 times of their defined half-life.
•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.
•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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Macrophage activation syndrome / Secondary hemophagocytic lymphohistiocytosis (MAS/sHLH) in patients with Systemic Juvenile Idiopathic Arthritis (sJIA)
MedDRA version: 19.1 Level: LLT Classification code 10053867 Term: Macrophage activation syndrome System Organ Class: 100000004851

Intervention(s)

Product Code: NI-0501
Pharmaceutical Form: Concentrate for solution for infusion

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: At multiple timepoints over 8 weeks

Secondary Objective: Not applicable

Main Objective: • To describe the pharmacokinetic profile of NI-0501 in sJIA patients with MAS
•To confirm the proposed dosing regimen of NI-0501
•To evaluate the safety and tolerability profile of intravenous administrations of NI-0501
•To preliminary assess the efficacy of NI-0501
•To assess the levels of relevant biomarkers
•To assess the immunogenicity of NI-0501

Primary end point(s): Safety and tolerability:
•Incidence, severity, causality and outcomes of AEs (serious and non-serious), with particular attention being paid to infections.
•Evolution of laboratory parameters, in particular CBC, LFTs, inflammatory markers (ferritin and CRP) and coagulation parameters.
•Number of patients withdrawn from the study due to safety reasons.

Pharmacokinetics and pharmacodynamics:
•PK profile of NI-0501.
•Levels of circulating free IFN? at predose, and total IFN? after initiation of NI-0501.
•Levels of the main IFN?-induced chemokines and other potential disease biomarkers.
•Levels (if any) of circulating antibodies against NI-0501 to determine immunogenicity.

Secondary Outcome(s)

Secondary end point(s): Efficacy:
•Number of patients achieving MAS remission by Week 8 after initiation of NI-0501 treatment.
•Time to MAS remission.
•Number of patients for whom at any time during the study glucocorticoids can be tapered i) to the same (or lower) dose being administered before the occurrence of MAS ((in those patients who are already treated for sJIA) or ii) by 50% (or less) of the dose administered at NI-0501 treatment start (in those patients who present with MAS at sJIA onset).
•Time to glucocorticoids tapering (as above described).
•Survival time.
•Number of patients withdrawn from the study due to lack of efficacy.

Timepoint(s) of evaluation of this end point: At multiple timepoints over 8 weeks

Secondary ID(s)

NI-0501-06

Source(s) of Monetary Support

Novimmune SA