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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02069899
Recruitment Status : Completed
First Posted : February 24, 2014
Results First Posted : June 28, 2022
Last Update Posted : June 28, 2022
Sponsor:
Collaborator:
Seventh Framework Programme
Information provided by (Responsible Party):
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).

Condition or disease Intervention/treatment Phase
Hemophagocytic Lymphohistiocytosis Drug: Emapalumab Phase 2 Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 58 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
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
Actual Study Start Date : August 4, 2014
Actual Primary Completion Date : May 18, 2021
Actual Study Completion Date : May 18, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Enrolled-04 Cohort

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.

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.
Other Name: NI-0501

No Intervention: Enrolled-06 Cohort

All participants who received at least 1 dose of emapalumab and were monitored for at least 4 weeks after the last drug administration in Study NI-0501-06 (NCT03311854) will be invited to participate for long-term follow-up for 1 year after the last administration of emapalumab.

Participants will not receive emapalumab in the current study (NI-0501-05, NCT02069899).

Enrolled-CU Cohort

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.

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.
Other Name: NI-0501




Primary Outcome Measures :
  1. Number of Participants With Adverse Event (AE) [ 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) ]
    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 :
  1. Cumulative Duration of Response (Enrolled-04 Cohort) [ Time Frame: 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).


  2. Duration of First Response (Enrolled-06 Cohort) [ Time Frame: 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.

  3. Overall Survival (Enrolled-04 Cohort) [ 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 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.


  4. Overall Survival (Enrolled-06 Cohort) [ 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 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.


  5. Percentage of Participants Who Achieved Engraftment (Enrolled-04 Cohort) [ Time Frame: 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.

  6. Percentage of Participants Who Achieved Donor Chimerism (Enrolled-04 Cohort) [ Time Frame: 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%.

  7. Percentage of Participants With Graft-versus-host-disease (Enrolled-04 Cohort) [ Time Frame: From HSCT to 12 months ]
    Occurrence of graft-versus-host-disease, reported in Study NI-0501-05 as an AE.

  8. MAS Activity Level as Assessed by Visual Analogue Scale (Enrolled-06 Cohort) [ Time Frame: 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.

  9. Circulating Emapalumab Level (Enrolled-04 Cohort) [ 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 in Enrolled-04 Cohort who continued to receive treatment with emapalumab in the current study (NI-0501-05).

  10. Circulating Emapalumab Level (Enrolled-06 Cohort) [ Time Frame: Baseline (first NI-0501-05 visit), Day 100, Month 6 ]
  11. 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 ]
  12. Total Human Interferon Gamma Levels (Enrolled-06 Cohort) [ Time Frame: Baseline (first NI-0501-05 visit), Day 100, Month 12/End of Study ]
  13. Number of Participants With Anti-drug Antibody [ Time Frame: From enrolment up to 12 months post-transplant or last emapalumab infusion (maximum 639 days) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02069899


Locations
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United States, Michigan
Spectrum Health Helen Devos Children's Hospital
Grand Rapids, Michigan, United States, 49503
United States, North Carolina
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
Cincinnati Children's Hospital - Division of Immunobiology
Cincinnati, Ohio, United States, 45229-3039
Cincinnati Children's Hospital
Cincinnati, Ohio, United States, 45229
United States, Texas
Texas Children's Cancer Center
Houston, Texas, United States, 77030
France
Hôpital Necker-Enfants Malades
Paris, France, 75743
Italy
Fondazione MBBM c/o Ospedale San Gerardo Clinica Pediatrica
Monza, Italy, 20900
Azienda Ospedaliera Padova
Padova, Italy, 35128
Ospedale Pediatrico Bambino Gesu - UO Reumatologia
Rome, Italy, 00165
Ospedale Pediatrico Bambino Gesu
Rome, Italy, 00165
Ospedale della Donna e del Bambino - U.O.C. Oncoematologia Pediatrica
Verona, Italy, 37126
Spain
Hospital Universitario Vall d'Hebron Servei de Hematologia i Oncologia
Barcelona, Spain, 08035
Sant Joan de Déu Hospital - Pediatric Rheumatology Department
Barcelona, Spain, 08950
Hospital Universitario Niño Jesús Servicio de Hemato-Oncología Pediátrica
Madrid, Spain, 28009
United Kingdom
UCL Institute of Child Health Great Ormond Street Hospital
London, United Kingdom, WC1N1EH
Great Ormond Street Hospital - Department of Haematology
London, United Kingdom, WC1N3JH
Sponsors and Collaborators
Swedish Orphan Biovitrum
Seventh Framework Programme
  Study Documents (Full-Text)

Documents provided by Swedish Orphan Biovitrum:
Study Protocol  [PDF] October 31, 2019
Statistical Analysis Plan  [PDF] March 26, 2021

Publications of Results:
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 Lymphohistiocytosis Treated with Emapalumab.Transplant Cell Ther. 2021; 27(Supplement 3): S118.
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

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Responsible Party: Swedish Orphan Biovitrum
ClinicalTrials.gov Identifier: NCT02069899    
Other Study ID Numbers: NI-0501-05
First Posted: February 24, 2014    Key Record Dates
Results First Posted: June 28, 2022
Last Update Posted: June 28, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Keywords provided by Swedish Orphan Biovitrum:
Hemophagocytic lymphohistiocytosis (HLH) previously treated with NI-0501
Emapalumab
Additional relevant MeSH terms:
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Lymphohistiocytosis, Hemophagocytic
Histiocytosis, Non-Langerhans-Cell
Histiocytosis
Lymphatic Diseases