E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Haemophagocytic lymphohistiocytosis |
|
E.1.1.1 | Medical condition in easily understood language |
A rare, life-threatening condition affecting predominantly children. The disease is characterized by uncontrolled inflammation. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10071583 |
E.1.2 | Term | Haemophagocytic lymphohistiocytosis |
E.1.2 | System Organ Class | 100000004851 |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To monitor the long-term safety profile of NI-0501
|
|
E.2.2 | Secondary objectives of the trial |
• 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.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Having received at least one dose of NI-0501 during a previous NI-0501 study or under a CU treatment protocol
2. Informed Consent by the patient or the patient’s legal representative(s), as applicable, with the assent of patients who are legally capable of providing it
3. Having agreed to continue using adequate methods of birth control until 6 months after the last administered dose of NI-0501, whenever relevant. Males with partners(s) of child-bearing potential must agree to take appropriate precautions to avoid fathering a child until 6 months after receiving last dose of NI-0501.
|
|
E.4 | Principal exclusion criteria |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Safety will be assessed as follows:
o Incidence, seriousness, intensity, relationship to NI-0501 and outcome of adverse events (AEs)
o Evolution over time of vital signs, physical examination and laboratory values
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Efficacy (as relevant, depending on the different patients’ characteristics):
o Duration of Response after completion of NI-0501 treatment (assessed according to the definitions set in the parent study)
o Survival time up to one year post-HSCT (including survival to HSCT and survival post-HSCT) or one year after last NI-0501 infusion (if transplant is not performed)
o Post-HSCT outcome indices, e.g. engraftment rate, donor chimerism, incidence of acute and chronic Graft versus Host Disease (GvHD) (it applies to patients who receive HSCT)
o Monitoring of background disease activity (it applies to patients with secondary forms of HLH)
Pharmacokinetics: NI-0501 elimination profile
Pharmacodynamics: IFNγ total
Immunogenicity: presence of ADAs
Exploratory PD parameters/endpoints: e.g. additional markers of disease activity
sCD25, CXCL9, CXCL10
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
France |
Italy |
Netherlands |
Spain |
Sweden |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 9 |