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

Hemophagocytic Lymphohistiocytosis Clinical Trial

Official title:

A Multicenter Study for the Long-term Follow-up of HLH Patients Who Received Treatment With NI-0501, an Anti-interferon Gamma Monoclonal Antibody

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02069899
• Other study ID #: NI-0501-05
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: August 4, 2014
• Est. completion date: May 18, 2021

Study information

• Verified date: May 2022
• Source: Swedish Orphan Biovitrum
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: May 18, 2021
• Est. primary completion date: May 18, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• None

Related Conditions & MeSH terms

• Hemophagocytic Lymphohistiocytosis
• Lymphohistiocytosis, Hemophagocytic

Intervention

Drug:
• Emapalumab
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.

Locations

Country	Name	City	State
France	Hôpital Necker-Enfants Malades	Paris
Italy	Fondazione MBBM c/o Ospedale San Gerardo Clinica Pediatrica	Monza
Italy	Azienda Ospedaliera Padova	Padova
Italy	Ospedale Pediatrico Bambino Gesu	Rome
Italy	Ospedale Pediatrico Bambino Gesu - UO Reumatologia	Rome
Italy	Ospedale della Donna e del Bambino - U.O.C. Oncoematologia Pediatrica	Verona
Spain	Hospital Universitario Vall d'Hebron Servei de Hematologia i Oncologia	Barcelona
Spain	Sant Joan de Déu Hospital - Pediatric Rheumatology Department	Barcelona
Spain	Hospital Universitario Niño Jesús Servicio de Hemato-Oncología Pediátrica	Madrid
United Kingdom	Great Ormond Street Hospital - Department of Haematology	London
United Kingdom	UCL Institute of Child Health Great Ormond Street Hospital	London
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Cincinnati Children's Hospital	Cincinnati	Ohio
United States	Cincinnati Children's Hospital - Division of Immunobiology	Cincinnati	Ohio
United States	Spectrum Health Helen Devos Children's Hospital	Grand Rapids	Michigan
United States	Texas Children's Cancer Center	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Swedish Orphan Biovitrum	Seventh Framework Programme

Countries where clinical trial is conducted

United States,  France,  Italy,  Spain,  United Kingdom, 

References & Publications (3)

Jordan MB, Locatelli F, Allen C, Cesaro S, Rizzari C, Rao A, Degar B, Garrington T, Sevilla J, Putti MC, Fagioli F, Ahlmann M, Dapena Diaz JL, Henry M, Grom A, De Benedetti F, de Min C. Post-Transplant Outcomes of Children with Primary Hemophagocytic Lymp

Laveille C, Jacqmin P, de Graaf K, de Min C. Population Pharmacokinetic Analysis of Emapalumab, a Fully Human, Anti-Interferon Gamma Monoclonal Antibody, in Children with Primary Hemophagocytic Lymphohistiocytosis. Blood 2020; 136 (Supplement 1): 20

Locatelli F, Jordan MB, Allen C, Cesaro S, Rizzari C, Rao A, Degar B, Garrington TP, Sevilla J, Putti MC, Fagioli F, Ahlmann M, Dapena Diaz JL, Henry M, De Benedetti F, Grom A, Lapeyre G, Jacqmin P, Ballabio M, de Min C. Emapalumab in Children with Primar — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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)
Secondary	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).	From 1st achievement of overall response until HSCT or last treatment date if participant did not undergo HSCT (maximum 250 days)
Secondary	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.	From first date of response and first date of loss of response or death (maximum 416 days)
Secondary	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.	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)
Secondary	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.	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)
Secondary	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.	From HSCT up to 12 months
Secondary	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%.	From HSCT to 12 months
Secondary	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.	From HSCT to 12 months
Secondary	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.	Baseline (first NI-0501-05 visit), Day 100, Month 12/End of Study
Secondary	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).	First infusion day (infusion duration: 1-2 hours) in Study NI-0501-05, last infusion day (infusion Day 188), 12 months post-transplant
Secondary	Circulating Emapalumab Level (Enrolled-06 Cohort)		Baseline (first NI-0501-05 visit), Day 100, Month 6
Secondary	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
Secondary	Total Human Interferon Gamma Levels (Enrolled-06 Cohort)		Baseline (first NI-0501-05 visit), Day 100, Month 12/End of Study
Secondary	Number of Participants With Anti-drug Antibody		From enrolment up to 12 months post-transplant or last emapalumab infusion (maximum 639 days)