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A Study to Investigate the Safety and Efficacy of an Anti-IFNγ mAb in Children Affected by Primary Haemophagocytic Lymphohistiocytosis

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ClinicalTrials.gov Identifier: NCT01818492
Recruitment Status : Completed
First Posted : March 26, 2013
Results First Posted : September 4, 2020
Last Update Posted : April 26, 2021
Sponsor:
Collaborator:
Seventh Framework Programme
Information provided by (Responsible Party):
NovImmune SA

Brief Summary:

The purpose of this study is to assess the safety, tolerability and efficacy of a new drug aimed at controlling disease activity in patients diagnosed with primary haemophagocytic lymphohistiocytosis. The new drug can be administered as the first-line therapy, to patients not previously treated with the current standard of care, or can be given to patients who have either failed or were unable to tolerate the current standard of care. Administration will be on top of a glucocorticosteroid, which is usually part of the current recommended treatment.

All participants in the NI-0501-04 study (NCT01818492) were invited to participate in the long-term follow-up study NI-0501-05 (NCT02069899). For the primary completion date, mentioned here, we refer to the NI-0501-04 study, even though in accordance with the NI-0501-04 study objectives, namely the assessment of long-term efficacy and safety endpoints, the study analyses also included data collected in the long-term follow-up study NI-0501-05. Hence these data are reported together. Study NI-0501-05 accepts patients from NI-0501-04 and NI-0501-06. Data collection for the patients from NI-0501-04 is completed.

The primary efficacy and safety analyses are based on the regulatory cut-off date of 20 July 2017. Refer to the publication in N Engl J Med 2020 May 7; 382 (19):1811-1822. Follow-on analyses have been conducted on all patients enrolled in the study, i.e. including the patients enrolled after the cut-off date of 20 July 2017. The results reported here refer to the totality of the 45 patients enrolled.


Condition or disease Intervention/treatment Phase
Primary Haemophagocytic Lymphohistiocytosis Biological: NI-0501 Phase 2 Phase 3

Detailed Description:

The purpose of this study is to assess the safety, tolerability and efficacy of a new drug aimed at controlling disease activity in patients diagnosed with primary haemophagocytic lymphohistiocytosis. The new drug can be administered as the first-line therapy, to patients not previously treated with the current standard of care, or can be given to patients who have either failed or were unable to tolerate the current standard of care. Administration will be on top of a glucocorticosteroid, which is usually part of the current recommended treatment.

All participants in the NI-0501-04 study (NCT01818492) were invited to participate in the long-term follow-up study NI-0501-05 (NCT02069899). For the primary completion date, mentioned here, we refer to the NI-0501-04 study, even though in accordance with the NI-0501-04 study objectives, namely the assessment of long-term efficacy and safety endpoints, the study analyses also included data collected in the long-term follow-up study NI-0501-05. Hence these data are reported together. Study NI-0501-05 accepts patients from NI-0501-04 and NI-0501-06. Data collection for the patients from NI-0501-04 is completed.

The primary efficacy and safety analyses are based on the regulatory cut-off date of 20 July 2017. Refer to the publication in N Engl J Med 2020 May 7; 382 (19):1811-1822. Follow-on analyses have been conducted on all patients enrolled in the study, i.e. including the patients enrolled after the cut-off date of 20 July 2017. The results reported here refer to the totality of the 45 patients enrolled.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 45 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2/3, Open-label, Single Arm, Multicentre Study to Assess Safety, Tolerability, Pharmacokinetics and Efficacy of Intravenous Multiple Administrations of NI-0501, an Anti-interferon Gamma (Anti-IFNγ) Monoclonal Antibody, in Paediatric Patients With Primary Haemophagocytic Lymphohistiocytosis
Actual Study Start Date : July 2013
Actual Primary Completion Date : January 2019
Actual Study Completion Date : January 2019


Arm Intervention/treatment
Experimental: NI-0501 Biological: NI-0501



Primary Outcome Measures :
  1. Overall Response Rate (ORR) at End of Treatment in Study NI-0501-04 (EOT 04) [ Time Frame: End of Treatment (3 days after the last infusion of emapalumab in study NI-0501-04, occurring between 4 and 8 weeks) ]

    Achievement of either Complete (CR) or Partial Response (PR), or HLH Improvement (HI) at End of Treatment of Study NI 0501-04 (EOT 04), based on pre-specified algorithm.

    CR: no fever, normal spleen size, no cytopenia (ANC ≥ 1.0x109/L and platelet count ≥ 100x109/L), no hyperferritinemia (serum ferritin <2000 μg), no coagulopathy (normal D-dimer and/or fibrinogen >150 mg/dL), no neurological and CSF abnormalities attributed to HLH, no sustained worsening of sCD25.

    PR: at least 3 HLH clinical and laboratory criteria (including 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 criteria (including CNS involvement).



Secondary Outcome Measures :
  1. Time to Response [ Time Frame: Assessed up to End of Treatment (3 days after the last infusion of emapalumab in study NI-0501-04, occurring between 4 and 8 weeks) ]
    Time from the date of the first dose of emapalumab to first achievement of response (at least HLH improvement)

  2. Durability of First Response [ Time Frame: Assessed up to End of Treatment (3 days after the last infusion of emapalumab in study NI-0501-04, occurring between 4 and 8 weeks) ]
    Maintenance of response achieved any time during the study

  3. Overall Survival [ Time Frame: Time from the date of first dose to last dose, or 8 weeks after first dose. ]
    Number of patients being alive at end of treatment or at week 8, pending on which comes first.

  4. Number of Patients Able to Reduce Glucocorticoids [ Time Frame: End of Treatment (3 days after the last infusion of emapalumab in study NI-0501-04, occurring between 4 and 8 weeks. ]
    Number of patients able to reduce glucocorticoids by 50% or more and between ≥30%-<50%, of baseline dose at EOT 04.

  5. Cumulative Duration of Response [ Time Frame: up to start of HSCT conditioning, whenever HSCT conditioning is scheduled (at least 4 weeks after treatment start), or End of Treatment 04/05 (if the patient did not have HSCT performed) ]
    Percent of treatment time in response from the first achievement of an Overall Response until HSCT conditioning, or End of Treatment 04/05 (if the patient did not have HSCT performed) Where applicable, data were collected in both NI-0501-04 and long-term follow-up study NI-0501-05.

  6. Survival Pre-HSCT [ Time Frame: Assessed up to HSCT, whenever HSCT occurred (up to approximately 6 months after treatment initiation) ]

    Time from the date of first dose to the date of death, expressed in Kaplan-Meier survival probability estimates. Patients who receive HSCT will be censored at that date; patients who did not receive HSCT will be censored at last date of contact.

    Where applicable, data were collected in both NI-0501-04 and long-term follow-up study NI-0501-05.


  7. Survival Post-HSCT [ Time Frame: Assessed up to Last Observation (up to 1 year after transplant, or up to approximately 18 months after treatment initiation) ]
    Time from the date of first dose to the date of death, expressed in Kaplan-Meier survival probability estimates. Patients without an event will be censored at last assessment date in either the NI-0501-04 or NI-0501-05 study. Patients who do not proceed to HSCT will be excluded from this analysis.



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Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Gender: male and female
  • Age: up to and including 18 years at diagnosis of Haemophagocytic Lymphohistiocytosis
  • Primary HLH patients
  • Patient (if ≥ 18 years old), or patient's legal representative(s) must have signed informed consent

Exclusion Criteria:

  • Diagnosis of secondary Haemophagocytic Lymphohistiocytosis consequent to a proven rheumatic or neoplastic disease.
  • Body weight < 3 kg.
  • Patients treated with biologics within a specific timeframe
  • Active Mycobacteria, Histoplasma Capsulatum, Shigella, Salmonella, Campylobacter and Leishmania infections.
  • Presence of malignancy.
  • Concomitant disease or malformation severely affecting the cardiovascular, pulmonary, liver or renal function

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): NCT01818492


Locations
Show Show 20 study locations
Sponsors and Collaborators
NovImmune SA
Seventh Framework Programme
  Study Documents (Full-Text)

Documents provided by NovImmune SA:
Study Protocol: US protocol  [PDF] March 24, 2016
Study Protocol: EU protocol  [PDF] February 26, 2016
Statistical Analysis Plan  [PDF] September 20, 2019

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: NovImmune SA
ClinicalTrials.gov Identifier: NCT01818492    
Other Study ID Numbers: NI-0501-04
2012-003632-23 ( EudraCT Number )
First Posted: March 26, 2013    Key Record Dates
Results First Posted: September 4, 2020
Last Update Posted: April 26, 2021
Last Verified: April 2021
Keywords provided by NovImmune SA:
Emapalumab
Additional relevant MeSH terms:
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Lymphohistiocytosis, Hemophagocytic
Histiocytosis, Non-Langerhans-Cell
Histiocytosis
Lymphatic Diseases