International, multicenter, long-term, follow-up study that will enrol HLH participants who have received emapalumab in previous clinical trials, in the context of the clinical development program for emapalumab or under compassionate use (CU).
The aim of this study is to monitor the long-term safety profile of emapalumab in participants who have previously received at least one dose of emapalumab, including survival time after the administration of emapalumab. Moreover, the elimination profile of emapalumab and the immunogenicity will also be assessed. Furthermore, safety, tolerability, efficacy, and pharmacokinetic (PK) profile of emapalumab will be closely monitored in the event that some participants, upon request of the treating physician, will receive emapalumab treatment in the follow-up study.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
58
Treatment with emapalumab is not planned for all enrolled participants. For participants who will continue receiving emapalumab in the context of this study (NI-0501-05), the dose and timing will be either carried forward from the last administered emapalumab dose as part of the parent study in which the participant was enrolled, or an adjusted dose will be administered, if necessary.
Spectrum Health Helen Devos Children's Hospital
Grand Rapids, Michigan, United States
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
Number of Participants With Adverse Event (AE)
Adverse events were defined as any undesirable experience occurring in a participant during the study, whether or not considered related to emapalumab.
Time frame: From the date of enrollment in this study up to 1 year either after HSCT or after the last administration of emapalumab (maximum duration: 639 days)
Cumulative Duration of Response (Enrolled-04 Cohort)
Cumulative duration of response: total number of days in response from 1st achievement of overall response until HSCT or last treatment date if the participant did not undergo HSCT. Overall response: achievement of either Complete (CR) or Partial Response (PR), or HLH Improvement (HI). CR: no fever, normal spleen size, no cytopenia (absolute neutrophil count \[ANC\] ≥1.0 x 10\^9/L and platelet count ≥ 100 x 10\^9/L), no hyperferritinemia (serum ferritin \<2000 μg/L), no coagulopathy (normal D-dimer and/or fibrinogen \>150 mg/dL), no neurological and cerebrospinal fluid \[CSF\] abnormalities attributed to HLH, no sustained worsening of soluble cluster of differentiation (CD) 25. PR: at least 3 HLH clinical and laboratory criteria (including central nervous system \[CNS\] abnormalities) met the CR criteria, no progression of other aspects of HLH disease pathology. HI: improvement (\>50% change from baseline) of at least 3 HLH clinical and laboratory abnormalities (including CNS involvement).
Time frame: From 1st achievement of overall response until HSCT or last treatment date if participant did not undergo HSCT (maximum 250 days)
Duration of First Response (Enrolled-06 Cohort)
Duration of first response was defined as the number of days between first date of response and first date of loss of response or death. Response was defined as macrophage activation syndrome (MAS) remission, which was resolution of clinical signs and symptoms according to the Investigator (MAS clinical signs and symptoms score ≤ 1) and normalization of laboratory parameters relevant to MAS as follows: white blood cells (WBC) and platelet count above the upper limit of normal (LLN), Lactate dehydrogenase \< 1.5 × lower limit of normal (ULN), aspartate aminotransferase/alanine aminotransferase \<1.5 × ULN, fibrinogen \> 100 mg/dL, ferritin level decreased by at least 80% from values at screening or baseline (whichever was higher) or \< 2000 ng/mL, whichever was lower.
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Cincinnati Children's Hospital - Division of Immunobiology
Cincinnati, Ohio, United States
Cincinnati Children's Hospital
Cincinnati, Ohio, United States
Texas Children's Cancer Center
Houston, Texas, United States
Hôpital Necker-Enfants Malades
Paris, France
Fondazione MBBM c/o Ospedale San Gerardo Clinica Pediatrica
Monza, Italy
Azienda Ospedaliera Padova
Padua, Italy
Ospedale Pediatrico Bambino Gesu - UO Reumatologia
Rome, Italy
Ospedale Pediatrico Bambino Gesu
Rome, Italy
...and 6 more locations
Time frame: From first date of response and first date of loss of response or death (maximum 416 days)
Overall Survival (Enrolled-04 Cohort)
Overall survival was defined as time from the date of the last emapalumab dose to the date of death. Participants without an event were censored at the time of last contact or 12 months after last dose (whichever came first). As some participants had their last emapalumab dose in the parent study (NI-0501-04), data from both NI-0501-05 and NI-0501-04 studies were considered for the assessment of overall survival. Kaplan-Meier methodology was used for estimation.
Time frame: From the date of last of emapalumab dose to the date of death or last contact or 12 months after last dose, whichever came first (maximum 366 days)
Overall Survival (Enrolled-06 Cohort)
Overall survival was defined as time from the date of last emapalumab dose to the date of death. Participants without an event were censored at the time of last contact or 12 months after last dose (whichever came first). As participants in the Enrolled-06 Cohort did not receive emapalumab in the current study, data from both NI-0501-05 and NI-0501-06 studies were considered for the assessment of overall survival. Kaplan-Meier methodology was used for estimation.
Time frame: From the date of last of emapalumab dose to the date of death or last contact or 12 months after last dose, whichever came first (maximum 366 days)
Percentage of Participants Who Achieved Engraftment (Enrolled-04 Cohort)
For participants who underwent HSCT either in parent study (NI-0501-04) or current study (NI-0501-05), engraftment rate was based on the number of participants experiencing primary or secondary graft failure (blood stem cell transplant failure, engraft failure, or transplant dysfunction), as reported as an adverse event.
Time frame: From HSCT up to 12 months
Percentage of Participants Who Achieved Donor Chimerism (Enrolled-04 Cohort)
For participants who underwent HSCT, achievement of donor chimerism was considered based on donor chimerism in peripheral blood completed, that is, donor cells \>95%.
Time frame: From HSCT to 12 months
Percentage of Participants With Graft-versus-host-disease (Enrolled-04 Cohort)
Occurrence of graft-versus-host-disease, reported in Study NI-0501-05 as an AE.
Time frame: From HSCT to 12 months
MAS Activity Level as Assessed by Visual Analogue Scale (Enrolled-06 Cohort)
MAS activity was monitored using a visual analogue scale ranging from 0 to 10 with a higher score indicted higher disease activity.
Time frame: Baseline (first NI-0501-05 visit), Day 100, Month 12/End of Study
Circulating Emapalumab Level (Enrolled-04 Cohort)
Circulating Emapalumab level in Enrolled-04 Cohort who continued to receive treatment with emapalumab in the current study (NI-0501-05).
Time frame: First infusion day (infusion duration: 1-2 hours) in Study NI-0501-05, last infusion day (infusion Day 188), 12 months post-transplant
Circulating Emapalumab Level (Enrolled-06 Cohort)
Time frame: Baseline (first NI-0501-05 visit), Day 100, Month 6
Total Human Interferon Gamma Levels (Enrolled-04 Cohort)
Time frame: First infusion day (infusion duration: 1-2 hours) in Study NI-0501-05, Day 100 post-transplant, 12 months post-transplant
Total Human Interferon Gamma Levels (Enrolled-06 Cohort)
Time frame: Baseline (first NI-0501-05 visit), Day 100, Month 12/End of Study
Number of Participants With Anti-drug Antibody
Time frame: From enrolment up to 12 months post-transplant or last emapalumab infusion (maximum 639 days)