A study to investigate the safety and efficacy of a new drug, NI-0501, in children with a disease that is called Haemophagocytic Lymphohistiocytosis which has reactivated or has not achieved a satisfactory response.
- Conditions
- Therapeutic area: Diseases [C] - Immune System Diseases [C20]Primary haemophagocytic lymphohistiocytosis which has reactivated or an unsatisfactory response has been achieved.MedDRA version: 17.1 Level: SOC Classification code 10010331 Term: Congenital, familial and genetic disorders System Organ Class: 10010331 - Congenital, familial and genetic disorders
- Registration Number
- EUCTR2012-003632-23-AT
- Lead Sponsor
- ovImmune SA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 10
1. Primary HLH patients of both genders, up to and including 18 years at diagnosis of HLH, who have been previously treated by conventional induction therapy
2. Patients must also,
a. Present Reactivation, or Worsening, or No Further Improvement of the disease (for at least 4 weeks from initiation of treatment) after having achieved at least Partial or Incomplete Response
OR
b. Show No Response for at least 2 weeks from initiation of treatment or Worsening of the disease
OR
c. Show Intolerance to conventional treatment of HLH, as judged by the treating physician
3. Diagnosis of primary HLH according to the following criteria (as per the 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.
In case the diagnosis of HLH is based on the 5 of the 8 above criteria (and not on a molecular finding or a familial history consistent with primary HLH), the patient is eligible to enter the study if there is
a. Reactivation, or Worsening, or No Further Improvement (for at least 4 weeks from initiation of treatment) of the disease after having achieved at least Partial or Incomplete Response. In this specific situation, Worsening and No Further Improvement must include abnormal sCD25 or ferritin > 2000 ng/ml
OR
b. No Response (for at least 2 weeks from initiation of treatment) or Worsening of the disease (without previous Partial or Incomplete Response). Soluble CD25 must be abnormal or ferritin > 2000 ng/ml and the evaluation and approval by the Scientific Steering Committee is mandatory (see definitions in Table 1)
OR
c. Intolerance to conventional treatment of HLH, as judged by the treating physician and approval by the Scientific Steering Committee is mandatory
4. Patients must have received treatment for HLH according to the conventional therapy at the site (e.g. corticosteroids alone or in combination with etoposide, CsA, methotrexate etc.). At the time of enrollment, eligible patients might still be receiving treatment (induction or maintenance) or might have already discontinued it.
5. Informed consent signed by the patient (if = 18 years old), or by the patient’s legal representative(s) with the assent of patients who are legally capable of providing it.
6. 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 p
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
• anti-CD20, as part of EBV infection treatment, within the previous week prior to screening
• any other biologic drug within 5 times their defined half-life period (a list of some of the most commonly used biologic half-lives will be included in the Study Specific Risk Management Plan)
4. Isolated or multiple acute organ failure(s) (heart, lung or kidney), requiring aggressive therapy such as high doses of inotropic drugs, circulatory assistance, hemofiltration or haemodialysis, artificial ventilation.
5. Active mycobacteria, Shigella, Campylobacter, Leishmania or Salmonella infections.
6. Evidence of past or active tuberculosis.
7. Positive serology for HIV antibodies, hepatitis B surface antigen or hepatitis C antibodies.
8. History of malignancy.
9. Patients who have another concomitant disease or malformation severely affecting cardiovascular, pulmonary, liver or renal function.
10. History of hypersensitivity or allergy to any component of the study regimen.
11. Vaccination with a live or attenuated live (including BCG) vaccine within the previous 12 weeks prior to screening.
12. Pregnant or lactating female patients.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method