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Hemophagocytic LymphohistiocytosisPhase 2/3NCT02069899

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

A Phase 2/3 study testing Emapalumab in people with Hemophagocytic Lymphohistiocytosis, run by Swedish Orphan Biovitrum at 16 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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). Read more about this study

Who is it for?
Any age
Conditions the study is for
Hemophagocytic Lymphohistiocytosis
What is being tested?
Emapalumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
58 participants
Where
16 sitesin 5 countries
Study dates
4 Aug 2014to 18 May 2021
Phase
Phase 2/3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • None

Trial locations and contacts

16 sites in 5 countries.

16 sites in 5 countries

United States5 sites

  • University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27599

  • Cincinnati Children's Hospital - Division of Immunobiology

    Cincinnati, Ohio, 45229-3039

  • Cincinnati Children's Hospital

    Cincinnati, Ohio, 45229

  • Spectrum Health Helen Devos Children's Hospital

    Grand Rapids, Michigan, 49503

  • Texas Children's Cancer Center

    Houston, Texas, 77030

Other trials in United States

Italy5 sites

  • Fondazione MBBM c/o Ospedale San Gerardo Clinica Pediatrica

    Monza, 20900

  • Azienda Ospedaliera Padova

    Padova, 35128

  • Ospedale Pediatrico Bambino Gesu - UO Reumatologia

    Rome, 00165

  • Ospedale Pediatrico Bambino Gesu

    Rome, 00165

  • Ospedale della Donna e del Bambino - U.O.C. Oncoematologia Pediatrica

    Verona, 37126

Other trials in Italy

Spain3 sites

  • Hospital Universitario Vall d'Hebron Servei de Hematologia i Oncologia

    Barcelona, 08035

  • Sant Joan de Déu Hospital - Pediatric Rheumatology Department

    Barcelona, 08950

  • Hospital Universitario Niño Jesús Servicio de Hemato-Oncología Pediátrica

    Madrid, 28009

Other trials in Spain

United Kingdom2 sites

  • UCL Institute of Child Health Great Ormond Street Hospital

    London, WC1N1EH

  • Great Ormond Street Hospital - Department of Haematology

    London, WC1N3JH

Other trials in United Kingdom

France1 site

  • Hôpital Necker-Enfants Malades

    Paris, 75743

Other trials in France

About this study

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

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).

Read the 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.

Being tested
Emapalumab
Keywords
Hemophagocytic lymphohistiocytosis (HLH) previously treated with NI-0501, Emapalumab
Medical subject headings
Lymphohistiocytosis, Hemophagocytic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EmapalumabDrug

    Also called NI-0501

    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.

Study groups in NCT02069899
Study groupRoleWhat they receive
Enrolled-04 CohortOtherParticipants 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.
Receives: Drug: Emapalumab
Enrolled-06 CohortNo interventionAll 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 CohortOtherIn 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.
Receives: Drug: Emapalumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 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 outcomes (13)

  1. 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).

    Measured: From 1st achievement of overall response until HSCT or last treatment date if participant did not undergo HSCT (maximum 250 days)

  2. 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.

    Measured: From first date of response and first date of loss of response or death (maximum 416 days)

  3. 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.

    Measured: 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)

  4. 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.

    Measured: 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)

  5. 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.

    Measured: From HSCT up to 12 months

  6. 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%.

    Measured: From HSCT to 12 months

  7. 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.

    Measured: From HSCT to 12 months

  8. 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.

    Measured: Baseline (first NI-0501-05 visit), Day 100, Month 12/End of Study

  9. 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).

    Measured: First infusion day (infusion duration: 1-2 hours) in Study NI-0501-05, last infusion day (infusion Day 188), 12 months post-transplant

  10. Circulating Emapalumab Level (Enrolled-06 Cohort)

    Measured: Baseline (first NI-0501-05 visit), Day 100, Month 6

  11. Total Human Interferon Gamma Levels (Enrolled-04 Cohort)

    Measured: 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)

    Measured: Baseline (first NI-0501-05 visit), Day 100, Month 12/End of Study

  13. Number of Participants With Anti-drug Antibody

    Measured: From enrolment up to 12 months post-transplant or last emapalumab infusion (maximum 639 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Feb 2014 (estimated)
  2. Study start4 Aug 2014
  3. Primary completion18 May 2021
  4. Study completion18 May 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Other
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
58 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02069899
Sponsor's protocol ID
NI-0501-05
Status last verified
May 2022
First submitted
23 Dec 2013
Last updated
28 Jun 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
Individual data sharing
No

Publications

  • 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

  • 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 Primary Hemophagocytic Lymphohistiocytosis. N Engl J Med. 2020 May 7;382(19):1811-1822. doi: 10.1056/NEJMoa1911326.

    PubMed 32374962

  • Brossard P, Laveille C. Population Pharmacokinetics of the Anti-Interferon-Gamma Monoclonal Antibody Emapalumab: An Updated Analysis. Rheumatol Ther. 2024 Jun;11(3):869-880. doi: 10.1007/s40744-024-00669-y. Epub 2024 Apr 25.

    PubMed 38662147

  • De Benedetti F, Grom AA, Brogan PA, Bracaglia C, Pardeo M, Marucci G, Eleftheriou D, Papadopoulou C, Schulert GS, Quartier P, Anton J, Laveille C, Frederiksen R, Asnaghi V, Ballabio M, Jacqmin P, de Min C. Efficacy and safety of emapalumab in macrophage activation syndrome. Ann Rheum Dis. 2023 Jun;82(6):857-865. doi: 10.1136/ard-2022-223739. Epub 2023 Mar 31.

    PubMed 37001971

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Emapalumab in people with Hemophagocytic Lymphohistiocytosis, run by Swedish Orphan Biovitrum at 16 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in United States, Italy, Spain, United Kingdom, France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Jun 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02069899, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2022.

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