A Multicentre, Randomised, Double-blind, Parallel-group, Placebo controlled, 24-week Phase 3 Study with an Open-label Extension to Evaluate the Efficacy and Safety of Benralizumab in Patients with Hypereosinophilic Syndrome (HES)

Benralizumab is an antibody (i.e. biologic drug) that has been made to reduce
the number of eosinophils in the body. A previous benralizumab HES study showed
that benralizumab may reduce eosinophils in blood and tissues in patients with
severe HES that is not well controlled by standard of care medications.
Benralizumab is not approved by any health authority for treatment of HES,
except for use in research studies like this. Health authorities are
authorities who supervise the study, who approve the commercialisation of the
drug or who receive the adverse events reporting, whether in your country or in
other countries. Benralizumab is an approved treatment for severe eosinophilic
asthma in the US, Europe, Canada and other countries under the trade name
Fasenra.

This study has been transitioned to CTIS with ID 2023-510455-28-00 check the CTIS register for the current data.

This study is being carried out to investigate the treatment with benralizumab
in patients with active HES.
The purpose of this study is to see if benralizumab, given as injections under
the skin, can help control your HES better if it is added to available standard
of care HES medications which you are currently taking.

This is a multicentre, randomised, Double-blind, parallel-group,
placebo-controlled, 24-week Phase 3 study to compare the efficacy and safety of
benralizumab 30 mg versus placebo administered by SC injection Q4W in patients
with HES.

The study is double-blind for the first 24 weeks, with 1:1 randomization to
benralizumab or placebo.
This is followed by an open-label part, at least 1 year for each participant,
in which benralizumab is given.

See Protocol V6.0 Part 4 Study Design

The Treatment options includes:

- Treatment with 1 investigational product; Benrazilumab vs placebo


See Protocol V6.0 Part 6 Study Treatment

Safety and tolerability data from the Phase 2 study of benralizumab in patients
with HES showed that benralizumab was well-tolerated, with similar rates of AEs
observed between active and placebo groups.

Total AEs, Grade 3 AEs, and the number of patients reporting an AE were similar
between the benralizumab and placebo groups. No new safety signals for
benralizumab were identified in this study of patients with HES.

Given the initial study results for benralizumab in HES, potential benefits of
this similarly designed Phase 3 study include: reduction in the incidence of
HES worsening/flare, reduction in haematological relapse, and improvement in
patient symptoms while exhibiting a safety profile similar to placebo.

Given the extensive safety data already available at the dosing regimen to be
studied, the benefit/risk profile in patients with HES is expected to continue
to be favourable, commensurate with that observed in the benralizumab asthma
pivotal trials and the HES Phase 2 study. Risk minimisation measures include
exclusion of patients with life-threatening HES and/or HES complication(s),
patients with a history of thrombotic complications, stroke, or significant
cardiac damage related to HES, untreated parasitic infection, a history of
anaphylaxis to any biologic therapy, active or recent malignancy, and exclusion
of pregnant women. Risk minimisation measures will be maintained during the
conduct of this study, in conjunction with the performance of the Sponsor*s
routine pharmacovigilance activities.

See protocol V6.0, Part 2.3 Benefit/Risk and Investigator Brochure Ed 19