A multicentre study for the long-term follow-up of HLH patients who received treatment with NI-0501, an anti-interferon gamma monoclonal antibody

Macrophage Activation Syndrome (MAS) is a secondary form of HLH often observed
in patients
suffering from a rheumatic disease, such as systemic Juvenile Idiopathic
Arthritis (sJIA) and Systemic
Lupus Erythematosus (SLE). MAS, like HLH, is characterized by sustained immune
cell activation and an associated cytokine storm of pro-inflammatory cytokines
with overproduction of IFNγ and other cytokines.

NI-0501 has been selected because it inactivates a protein called interferon
gamma (IFNγ) which is believed to be responsible for the inflammation and
tissue damage in MAS patients. Therefore, by neutralizing IFNγ, the
inflammation present in the body may be halted, stopping organ damage and
restoring a healthier condition.

Beyond the demonstration of the safety, tolerability and efficacy of NI-0501 as
induction treatment
for HLH and as treatment for MAS, there is a need to establish the mid- and
long-term safety of NI-
0501 treatment and its influence on survival of patients.

Currently, 2 interventional studies are ongoing: an open-label Phase 2/3 study
in patients with pHLH
(protocol NI-0501-04) and a pilot study in MAS in sJIA patients (protocol
NI-0501-06).
In addition, NI-0501 has been administered under a compassionate use treatment
protocol to HLH
patients that exhausted all available therapeutic options.
Study NI-0501-05 allows a systematic collection of long-term data in patients
previously exposed to
NI-0501 during the course of the studies mentioned above (and potentially other
studies not yet
ongoing) or who have received NI-0501 in compassionate use.

This is an international multicentre long-term follow-up study of HLH patients
who have received at
least one dose of NI-0501 in the context of a previous NI-0501 clinical study
in which no long-term
follow-up is already planned.

Study Objectives:
* To monitor the long-term safety profile of NI-0501
* To assess HLH patients* survival after NI-0501 treatment
* To assess duration of response to NI-0501 treatment (i.e. maintenance of HLH
control)
* To assess post-HSCT outcome measures, if applicable
* To assess background disease activity, in patients with secondary forms of HLH
* To study the elimination profile of NI-0501
* To evaluate the pharmacodynamic (PD) effects (levels of circulating Total
IFNγ, CXCL9, CXCL10)
* To assess the profile of relevant HLH biomarkers, e.g., sCD25
* To assess the immunogenicity of NI-0501.

long-term follow-up of HLH patients who
received treatment with NI-0501

To date, NI-0501 has been given to 14 healthy adult volunteers and more than 50
patients with HLH. No safety concerns have so far been identified and no long
term effect has been attributed to NI-0501. Certain risks related to it may
still present as long as NI-0501 is detectable. Subjects participating in this
long-term follow-up study will ensure that the medical condition and any
effects of NI-0501 are monitored longer. and that his/her study doctor can take
appropriate actions if needed. Data collected could help other patients with
the same type of disease in the near future.