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.

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.

Conditions

• Graft Failure

Interventions

DRUG

Emapalumab

Emapalumab is a fully human immunoglobulin G1 (IgG1) anti-IFNγ monoclonal antibody that binds to and neutralizes IFNγ. Emapalumab binds to both soluble and receptor (IFNγR1)-bound forms of IFNγ. Emapalumab is in development for treatment of primary and secondary HLH. The benefit expected from the targeted neutralization of IFNγ by emapalumab has been validated by the recent FDA approval of emapalumab for treatment of patients with pHLH who have refractory, recurrent or progressive disease or intolerance with conventional HLH therapy. The safety profile has been assessed as acceptable. Emapalumab will be administered by intravenous infusion over 1 to 2 hours, depending on the volume of the infusion. The first infusion must be performed within 12 hours after CXCL9 levels have been measured above defined threshold. Treatment will last until maximum dose 15 (up to 56 days) or until evidence of engraftment, whichever comes first.

Sponsors & Collaborators

• PRA Health Sciences

  collaborator INDUSTRY

• Cytel Inc.

  collaborator INDUSTRY

• Q2 Solutions

  collaborator INDUSTRY

• ABF Pharmaceutical Services GmbH

  collaborator INDUSTRY

• Cromsource

  collaborator INDUSTRY

• BioMérieux

  collaborator INDUSTRY

• Swedish Orphan Biovitrum

  lead INDUSTRY

Principal Investigators

• Tsila Zuckerman, Dr · The Rambam Academic Hospital

• Henrique Bittencourt, Dr · St. Justine's Hospital

• Polina Stepensky, Dr · Hadassah Hebrew University

• Ashvind Prabahran, Dr · Peter MacCallum Cancer Centre, Australia

• Richard Mitchell, Dr · Kids Cancer Centre Sydney Children's Hospital

Study Design

Allocation

NA

Purpose

PREVENTION

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

1 Year

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-05-25

Primary Completion

2022-04-21

Completion

2022-04-21

FDA Drug

Yes

Countries

• Australia
• Canada
• Israel

Study Locations