Study to Investigate Safety, Efficacy of an Anti-IFNγ mAb in Children With Primary Haemophagocytic Lymphohistiocytosis

A Phase 2/3 Open-label Single Arm Multicentre Study to Assess Safety Tolerability Pharmacokinetics and Efficacy of i.v. Administrations of NI-0501 an Anti-IFNγ mAb in Paediatric Patients With Primary Haemophagocytic Lymphohistiocytosis

The purpose of this study is to assess the safety, tolerability and efficacy of a new drug aimed at controlling disease activity in patients diagnosed with primary haemophagocytic lymphohistiocytosis. The new drug can be administered as the first-line therapy, to patients not previously treated with the current standard of care, or can be given to patients who have either failed or were unable to tolerate the current standard of care. Administration will be on top of a glucocorticosteroid, which is usually part of the current recommended treatment.

The purpose of this study is to assess the safety, tolerability and efficacy of a new drug aimed at controlling disease activity in patients diagnosed with primary haemophagocytic lymphohistiocytosis. The new drug can be administered as the first-line therapy, to patients not previously treated with the current standard of care, or can be given to patients who have either failed or were unable to tolerate the current standard of care. Administration will be on top of a glucocorticosteroid, which is usually part of the current recommended treatment.

All participants in the NI-0501-04 study (NCT01818492) were invited to participate in the long-term follow-up study NI-0501-05 (NCT02069899). For the primary completion date, mentioned here, we refer to the NI-0501-04 study, even though in accordance with the NI-0501-04 study objectives, namely the assessment of long-term efficacy and safety endpoints, the study analyses also included data collected in the long-term follow-up study NI-0501-05. Hence these data are reported together. Study NI-0501-05 accepts patients from NI-0501-04 and NI-0501-06. Data collection for the patients from NI-0501-04 is completed.

The primary efficacy and safety analyses are based on the regulatory cut-off date of 20 July 2017. Refer to the publication in N Engl J Med 2020 May 7; 382 (19):1811-1822. Follow-on analyses have been conducted on all patients enrolled in the study, i.e. including the patients enrolled after the cut-off date of 20 July 2017. The results reported here refer to the totality of the 45 patients enrolled.

Inclusion Criteria:

• Gender: male and female
• Age: up to and including 18 years at diagnosis of Haemophagocytic Lymphohistiocytosis
• Primary HLH patients
• Patient (if ≥ 18 years old), or patient's legal representative(s) must have signed informed consent

Exclusion Criteria:

• Diagnosis of secondary Haemophagocytic Lymphohistiocytosis consequent to a proven rheumatic or neoplastic disease.
• Body weight < 3 kg.
• Patients treated with biologics within a specific timeframe
• Active Mycobacteria, Histoplasma Capsulatum, Shigella, Salmonella, Campylobacter and Leishmania infections.
• Presence of malignancy.
• Concomitant disease or malformation severely affecting the cardiovascular, pulmonary, liver or renal function