Study to Investigate the Pharmacokinetics, Pharmacodynamics and Assess the Efficacy and Safety to Support Dose Selection of Emapalumab in Pre-empting Graft Failure in Patients at High Risk After HSCT.
brief summary
This study is designed as an open-label, single arm, proof of concept study in order to determine the appropriate emapalumab dosing regimen neutralizing IFNγ in patients at risk of GF. Patients presenting CXCL9 levels above a defined threshold and other clinical criteria will be eligible to receive emapalumab. Both children and adults, with malignant and non-malignant underlying diseases, receiving allo-HSCT who are at high risk of GF as defined in the inclusion criteria will be included in the study. The main objective of the study is to determine the appropriate emapalumab dose regimen neutralizing interferon gamma (IFNγ) activity to pre-empt graft failure post allo-HSCT in a population with various underlying diseases and at high risk of graft failure (GF). Maximum 3 cohorts are foreseen to determine the appropriate dose regimen to pre-emptively treat patients at risk of primary GF. Emapalumab will be administered by IV infusion and treatment will last up to 56 days (15 infusions) or until evidence of engraftment. The study is expected to last approximately 3 years from screening to the last follow-up phone call for each patient.
detailed description
This study is designed as an open-label, single arm, proof of concept study in order to determine the appropriate emapalumab dosing regimen neutralizing IFNγ in patients at risk of GF. Patients presenting CXCL9 levels above a defined threshold and other clinical criteria will be eligible to receive emapalumab.
Both children and adults, with malignant and non-malignant underlying diseases, receiving allo-HSCT who are at high risk of GF as defined in the inclusion criteria will be included in the study. The main objective of the study will be to determine the appropriate emapalumab dose regimen neutralizing interferon gamma (IFNγ) activity to pre-empt graft failure post allo-HSCT in a population with various underlying diseases and at high risk of graft failure (GF).
Maximum 3 cohorts are foreseen to determine the appropriate dose regimen to pre-emptively treat patients at risk of primary GF.
Emapalumab will be administered by IV infusion over 1 to 2 hours depending on the volume of the infusion. Treatment will last up to 56 days (15 infusions) or until evidence of engraftment.
The study is comprised of the following study periods: screening (Day -21 to Day -8), allogeneic HSCT Day 0, monitoring period for primary GF (Day 1 up to Day 42), extended monitoring for secondary GF (up to Day 98), treatment period (up to 56 days) and follow-up period of 3 years after HSCT.
The main objective of this proof of concept study is:
• To determine the appropriate emapalumab dose regimen neutralizing interferon gamma (IFNγ) activity to pre-empt graft failure post allogeneic hematopoietic stem cell transplantation (HSCT) in a population with various underlying diseases and at high risk of graft failure (GF)
The following objectives will support the dose selection:
* To describe the Pharmacokinetic (PK) and Pharmacodynamic (PD) profiles of emapalumab post allogeneic HSCT (allo-HSCT) * To assess the efficacy of emapalumab to pre-empt GF post allo-HSCT * To assess the safety of emapalumab to pre-empt GF post allo-HSCT * To assess the immunogenicity of emapalumab post allo-HSCT
Exploratory objectives will be:
• To evaluate further data on the correlation between relevant biomarkers including C-X-C motif chemokine ligand 9 (CXCL9) levels and the risk of GF post allo-HSCT in a population with various underlying diseases and at high risk of GF also in the context of development of a diagnostic test.
official title
An Open Label, Single Arm, Multicentre, Proof of Concept, Phase 2 Study to Investigate the Pharmacokinetics, Pharmacodynamics and Assess the Efficacy and Safety to Support Dose Selection of Emapalumab in Pre-empting Graft Failure in Patients at High Risk After Allogeneic Hematopoietic Stem Cell Transplantation