NI-0501-04

Principal Investigator: Mark Fluchel
Keywords: Pharmacokinetics , NI0501 , Hemophagocytic , Lymphohistioytosis Department: Pediatric Administration
IRB Number: 00081572 Co Investigator:  
Specialty: Clinical Immunology/Immunodeficiency
Sub Specialties:
Recruitment Status: Recruiting

Contact Information

Deveree Partridge
deveree.partridge@hsc.utah.edu
801-662-4710

Brief Summary

  • To determine the safety and tolerability profile of multiple intravenous (IV) administrations of NI-0501.
  • To determine NI-0501 efficacy and benefit/risk profile in HLH patients.
  • To describe the pharmacokinetics (PK) profile of NI-0501 in HLH patients.
  • To define an appropriate NI-0501 therapeutic dose regimen for HLH.
  • To assess the immunogenicity of NI-0501.

Inclusion Criteria

1. Primary HLH patients of both genders, up to and including 18 yearsi at diagnosis of HLH. The diagnosis of HLH must be made on the basis of the following criteria (as per HLH-2004 protocol):
a. A molecular diagnosis or familial history consistent with primary HLH
OR
b. Five out of the eight criteria below are fulfilled:
- Fever
- Splenomegaly
- Cytopenias affecting 2 of 3 lineages in the peripheral blood (hemoglobin < 90 g/L; platelets < 100 x 109/L; neutrophils < 1 x 109/L)
- Hypertriglyceridemia (fasting triglycerides ≥ 3 mmol/L or ≥ 265 mg/dL) and/or hypofibrinogenemia (≤ 1.5 g/L)
- Hemophagocytosis in bone marrow, spleen or lymph nodes, with no evidence of malignancy
- Low or absent natural killer (NK)-cell activity
- Ferritin ≥ 500 μg/L
- Soluble CD25 (sCD25; i.e. soluble IL-2 receptor) ≥ 2400 U/mL.
 
2. Presence of active disease in patients as assessed by the treating physician.
 
3. Patients having already received HLH conventional therapy must fulfill one of the following criteria as assessed by the treating physician and approved by the Scientific Steering Committee (SSC):
- Having not responded
- Having not achieved a satisfactory response
- Having not maintained a satisfactory response
- Showing intolerance to conventional treatment of HLH.
At the time of enrollment, eligible patients might still be receiving treatment (induction or maintenance) or might have already discontinued it.
 
4. Informed consent signed by the patient (if ≥ 18 years old), or by the patient‟s legally authorized representative(s) with the assent of patients who are legally capable of providing it.
 
5. Having received guidance on contraception for both male and female patients sexually active and having reached puberty.
Females of child-bearing potential, having a negative pregnancy test at screening, and unless true abstinence is in line with the preferred and usual lifestyle of the patient, must agree to use adequate method(s) of birth control from screening until 6 months after receiving last dose of the study drug. Males with partners(s) of child-bearing potential must agree to take appropriate precautions to avoid fathering a child from screening until 6 months after receiving last dose of the study drug.

Exclusion Criteria

1. Diagnosis of secondary HLH consequent to a proven rheumatic or neoplastic disease.
 
2. Body weight < 3 kg.
 
3. Patients treated with:
  • any T-cell depleting agents (such as anti-thymocyte globulin [ATG], anti-CD52) during the previous 2 weeks prior to screening
  • any other biologic drug within 5 times their defined half-life period (except for rituximab in case of documented EBV infection). A list of some of the most commonly used biologic half-lives will be included in the Development Risk Management Plan.
4. Active mycobacteria, Histoplasma Capsulatum, Shigella, Salmonella, Campylobacter or Leishmania infections.
 
5. Evidence of past history of tuberculosis or of latent tuberculosis.
 
6. Positive serology for HIV antibodies, hepatitis B surface antigen or hepatitis C antibodies.
 
7. Presence of malignancy.
 
8. Patients who have another concomitant disease or malformation severely affecting cardiovascular, pulmonary, liver or renal function.
 
9. History of hypersensitivity or allergy to any component of the study regimen.
 
10. Vaccination with a live or attenuated live (including BCG) vaccine within the previous 12 weeks prior to screening.
 
11. Pregnant or lactating female patients.