Primary Haemophagocytic Lymphohistiocytosis Clinical Trial
Official title:
A Phase 2/3 Open-label Single Arm Multicentre Study to Assess Safety Tolerability Pharmacokinetics and Efficacy of i.v. Administrations of NI-0501 an Anti-IFNγ mAb in Paediatric Patients With Primary Haemophagocytic Lymphohistiocytosis
| Verified date | April 2021 |
| Source | Swedish Orphan Biovitrum |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 45 |
| Est. completion date | January 2019 |
| Est. primary completion date | January 2019 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | N/A to 18 Years |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| Germany | University Children's Hospital | Münster | |
| Italy | Azienda Ospedaliero Universitaria Meyer | Florence | |
| Italy | Istituto Giannina Gaslini | Genoa | |
| Italy | Azienda Ospedaliera San Gerardo | Monza | |
| Italy | Azienda Ospedaliera Padova - Clinica di Oncoematologia Pediatrica | Padua | |
| Italy | Ospedale Pediatrico Bambino Gesu' | Roma | |
| Italy | Ospedale Donna Bambino - U.O.C. Oncoematologia Pediatrica | Verona | |
| Spain | Hospital Sant Joan de Déu | Barcelona | |
| Spain | Hospital Universitario Vall d'Hebron | Barcelona | |
| Spain | Hospital Universitario Niño Jesús | Madrid | |
| Sweden | Karolinska University Hospital | Stockholm | |
| United Kingdom | Great Ormond Street Hospital - Department of Haematology | London | |
| United States | Children's Healthcare of Atlanta | Atlanta | Georgia |
| United States | Children's Hospital Colorado | Aurora | Colorado |
| United States | Dana-Farber Cancer Institute (DFCI) | Boston | Massachusetts |
| United States | University of North Carolina at Chapel Hill | Chapel Hill | North Carolina |
| United States | Cincinnati Children's Hospital - Division of Immunobiology - Department of Pediatrics | Cincinnati | Ohio |
| United States | Texas Children's Cancer Center | Houston | Texas |
| United States | Primary Children's Hospital | Salt Lake City | Utah |
| United States | Alfred I. duPont Hospital for Children - Nemours Center for Cancer and Blood Disorders - Division of Pediatric Hematology Oncology | Wilmington | Delaware |
| Lead Sponsor | Collaborator |
|---|---|
| Swedish Orphan Biovitrum | Seventh Framework Programme |
United States, Germany, Italy, Spain, Sweden, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Overall Response Rate (ORR) Second Line | 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). |
End of Treatment (3 days after the last infusion of emapalumab in study NI-0501-04, occurring between 4 and 8 weeks) | |
| Primary | Overall Response Rate (ORR) All Treated | 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). |
End of Treatment (3 days after the last infusion of emapalumab in study NI-0501-04, occurring between 4 and 8 weeks) | |
| Primary | Overall Response Rate (ORR) Follow-on Analysis Set: | 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). |
End of Treatment (3 days after the last infusion of emapalumab in study NI-0501-04, occurring between 4 and 8 weeks) | |
| Primary | Overall Response Rate (ORR) at End of Treatment in Study NI-0501-04 (EOT 04) Follow-on Analysis Set: All Treated | 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). |
End of Treatment (3 days after the last infusion of emapalumab in study NI-0501-04, occurring between 4 and 8 weeks) | |
| Secondary | Time to Response | Time from the date of the first dose of emapalumab to first achievement of response (at least HLH improvement) | 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) | |
| Secondary | Durability of First Response | Maintenance of response achieved any time during the study | 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) | |
| Secondary | Overall Survival | Number of patients being alive at end of treatment or at week 8, pending on which comes first. | Time from the date of first dose to last dose, or 8 weeks after first dose. | |
| Secondary | Number of Patients Able to Reduce Glucocorticoids | Number of patients able to reduce glucocorticoids by 50% or more and between =30%-<50%, of baseline dose at EOT 04. | End of Treatment (3 days after the last infusion of emapalumab in study NI-0501-04, occurring between 4 and 8 weeks. | |
| Secondary | Cumulative Duration of Response | 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. | 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) | |
| Secondary | Survival Pre-HSCT | 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. |
Assessed up to HSCT, whenever HSCT occurred (up to approximately 6 months after treatment initiation) | |
| Secondary | Survival Post-HSCT | 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. | Assessed up to Last Observation (up to 1 year after transplant, or up to approximately 18 months after treatment initiation) |