A Study for Long-term Follow-up of Hemophagocytic Lymphohistiocytosis (HLH) Participants Who Received Treatment With Emapalumab (NI-0501), an Anti-interferon Gamma Monoclonal Antibody
- Registration Number
- NCT02069899
- Lead Sponsor
- Swedish Orphan Biovitrum
- Brief Summary
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).
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 58
- Having received at least one dose of emapalumab.
- Having signed the Informed Consent by the participant or the participant's legal representative(s), as applicable, with the assent of participant who are legally capable of providing it.
- None
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Enrolled-04 Cohort Emapalumab Participants enrolled in Study NI-0501-04 (NCT01818492) will be invited to participate for long-term follow-up for 1 year either after haematopoietic stem cell transplantation (HSCT) or after the last administration of emapalumab. In Study NI-0501-04, participants received emapalumab for 4 to 8 weeks. After the treatment period, participants could have undergone HSCT. Participants for whom an appropriate donor was not identified by Week 8, or in a case where HSCT will be delayed for reasons unrelated to the administration of emapalumab, can continue receiving treatment with emapalumab beyond the foreseen 8 weeks in the current study (NI-0501-05, NCT02069899) at the request of the investigator, providing a favorable benefit/risk assessment of treatment is established. The dose and timing was either carried forward from the last administered emapalumab dose as part of the parent protocol or an adjusted dose was administered, if necessary. Enrolled-CU Cohort Emapalumab In exceptional cases, at the spontaneous request of a treating physician, CU treatment will be granted to the participants who had exhausted all possible treatment options and who could not be enrolled in a clinical study. All participants who receive at least 1 dose of emapalumab under CU will be invited to participate for long-term follow-up for 1 year either after HSCT or after the last administration of emapalumab. Participants can continue treatment in the context of the current Study (NI-0501-05, NCT02069899) while stem cell donor search is ongoing, or if the investigator assesses that continuation of treatment is beneficial.
- Primary Outcome Measures
Name Time Method Number of Participants With Adverse Event (AE) 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) Adverse events were defined as any undesirable experience occurring in a participant during the study, whether or not considered related to emapalumab.
- Secondary Outcome Measures
Name Time Method Circulating Emapalumab Level (Enrolled-06 Cohort) Baseline (first NI-0501-05 visit), Day 100, Month 6 Total Human Interferon Gamma Levels (Enrolled-04 Cohort) 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) Baseline (first NI-0501-05 visit), Day 100, Month 12/End of Study Percentage of Participants Who Achieved Engraftment (Enrolled-04 Cohort) From HSCT up to 12 months 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.
Percentage of Participants Who Achieved Donor Chimerism (Enrolled-04 Cohort) From HSCT to 12 months For participants who underwent HSCT, achievement of donor chimerism was considered based on donor chimerism in peripheral blood completed, that is, donor cells \>95%.
MAS Activity Level as Assessed by Visual Analogue Scale (Enrolled-06 Cohort) Baseline (first NI-0501-05 visit), Day 100, Month 12/End of Study MAS activity was monitored using a visual analogue scale ranging from 0 to 10 with a higher score indicted higher disease activity.
Circulating Emapalumab Level (Enrolled-04 Cohort) 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 in Enrolled-04 Cohort who continued to receive treatment with emapalumab in the current study (NI-0501-05).
Percentage of Participants With Graft-versus-host-disease (Enrolled-04 Cohort) From HSCT to 12 months Occurrence of graft-versus-host-disease, reported in Study NI-0501-05 as an AE.
Number of Participants With Anti-drug Antibody From enrolment up to 12 months post-transplant or last emapalumab infusion (maximum 639 days) Cumulative Duration of Response (Enrolled-04 Cohort) From 1st achievement of overall response until HSCT or last treatment date if participant did not undergo HSCT (maximum 250 days) 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).Duration of First Response (Enrolled-06 Cohort) From first date of response and first date of loss of response or death (maximum 416 days) 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.
Overall Survival (Enrolled-04 Cohort) 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 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.Overall Survival (Enrolled-06 Cohort) 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 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.
Trial Locations
- Locations (16)
Great Ormond Street Hospital - Department of Haematology
🇬🇧London, United Kingdom
Azienda Ospedaliera Padova
🇮🇹Padova, Italy
Ospedale della Donna e del Bambino - U.O.C. Oncoematologia Pediatrica
🇮🇹Verona, Italy
UCL Institute of Child Health Great Ormond Street Hospital
🇬🇧London, United Kingdom
Hôpital Necker-Enfants Malades
🇫🇷Paris, France
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
Texas Children's Cancer Center
🇺🇸Houston, Texas, United States
Fondazione MBBM c/o Ospedale San Gerardo Clinica Pediatrica
🇮🇹Monza, Italy
Cincinnati Children's Hospital - Division of Immunobiology
🇺🇸Cincinnati, Ohio, United States
Cincinnati Children's Hospital
🇺🇸Cincinnati, Ohio, United States
Ospedale Pediatrico Bambino Gesu - UO Reumatologia
🇮🇹Rome, Italy
Hospital Universitario Vall d'Hebron Servei de Hematologia i Oncologia
🇪🇸Barcelona, Spain
Ospedale Pediatrico Bambino Gesu
🇮🇹Rome, Italy
Sant Joan de Déu Hospital - Pediatric Rheumatology Department
🇪🇸Barcelona, Spain
Hospital Universitario Niño Jesús Servicio de Hemato-Oncología Pediátrica
🇪🇸Madrid, Spain