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

NCT02069899 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: NI-0501-05
• Study Type: interventional
• Target: 58
• Locations: 5 countries
• Sites: 16

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).

Conditions

Hemophagocytic Lymphohistiocytosis

Keywords

Hemophagocytic lymphohistiocytosis (HLH) previously treated with NI-0501; Emapalumab

Outcome Measures

Primary Outcomes (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.

  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)

• 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)

• Duration of First Response (Enrolled-06 Cohort)

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

• 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 (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)

• Percentage of Participants Who Achieved Engraftment (Enrolled-04 Cohort)

  From HSCT up to 12 months

Study Arms (3)

Enrolled-04 Cohort

OTHER

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

Enrolled-06 Cohort

NO INTERVENTION

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

OTHER

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

Interventions

Emapalumab DRUG

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.

Also known as: NI-0501

Enrolled-04 Cohort; Enrolled-CU Cohort

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• None

Sponsors & Collaborators

• Swedish Orphan Biovitrum: lead
• Seventh Framework Programme: collaborator

Study Sites (16)

Spectrum Health Helen Devos Children's Hospital

Grand Rapids, Michigan, 49503, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Cincinnati Children's Hospital - Division of Immunobiology

Cincinnati, Ohio, 45229-3039, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

Texas Children's Cancer Center

Houston, Texas, 77030, United States

Location

Hôpital Necker-Enfants Malades

Paris, 75743, France

Location

Fondazione MBBM c/o Ospedale San Gerardo Clinica Pediatrica

Monza, 20900, Italy

Location

Azienda Ospedaliera Padova

Padua, 35128, Italy

Location

Ospedale Pediatrico Bambino Gesu - UO Reumatologia

Rome, 00165, Italy

Location

Ospedale Pediatrico Bambino Gesu

Rome, 00165, Italy

Location

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

Verona, 37126, Italy

Location

Hospital Universitario Vall d'Hebron Servei de Hematologia i Oncologia

Barcelona, 08035, Spain

Location

Sant Joan de Déu Hospital - Pediatric Rheumatology Department

Barcelona, 08950, Spain

Location

Hospital Universitario Niño Jesús Servicio de Hemato-Oncología Pediátrica

Madrid, 28009, Spain

Location

UCL Institute of Child Health Great Ormond Street Hospital

London, WC1N1EH, United Kingdom

Location

Great Ormond Street Hospital - Department of Haematology

London, WC1N3JH, United Kingdom

Location

Related Publications (5)

• 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.

  RESULT

• 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

  RESULT

• 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.

  PMID: 32374962 RESULT

• 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.

  PMID: 38662147 DERIVED

• 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.

  PMID: 37001971 DERIVED

MeSH Terms

Conditions

Lymphohistiocytosis, Hemophagocytic

Interventions

Emapalumab

Condition Hierarchy (Ancestors)

Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Radmila Kanceva/Senior Medical Director Immunology
• Organization: Sobi AG

Radmila.Kanceva@sobi.com

+ 41 22 551 91 63

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2013
• First Posted: February 24, 2014
• Study Start: August 4, 2014
• Primary Completion: May 18, 2021
• Study Completion: May 18, 2021
• Last Updated: June 28, 2022
• Results First Posted: June 28, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (5); IT (5); FR (1); ES (3); GB (2)