Open-Label, Long Term Safety and Efficacy Study of ISIS 721744 in the Prophylactic Treatment of HAE
Research type
Research Study
Full title
An Open-Label, Long Term Safety and Efficacy Study of Donidalorsen in the Prophylactic Treatment of Hereditary Angioedema (HAE)
IRAS ID
1005777
Contact name
Nancy Johansen
Contact email
Sponsor organisation
IONIS PHARMACEUTICALS, INC.
Eudract number
2022-000757-93
Clinicaltrials.gov Identifier
Research summary
Hereditary angioedema (HAE) is a rare genetic disorder that is characterised by recurrent episodes (also referred to as attacks) of severe swelling of the skin, painful abdominal attacks, and, occasionally, attacks in the upper airways (e.g. larynx and tongue) that can be
life-threatening. The age at which attacks begin varies, but most people have their first one in childhood or adolescence. The frequency of attacks usually increases after puberty.Attacks may involve one area of the body at a time, or they may involve a combination of areas. They always go away on their own but last from 2 to 4 days. While people with HAE have reported various triggers of attacks, emotional stress, physical stress, and dental
procedures are the most commonly reported triggers. There are 3 main types of HAE Types I and II are caused by a mutation in the SERPING1
gene, resulting in either a reduced level of C1 inhibitor protein (Type 1) or a dysfunction C1 inhibitor protein (Type II). The cause of Type III HAE, also known as HAE-nl-C1-INH, is varied and typically caused by problems with other genes such as the F12 gene, plasminogen gene,
the angiopoietin-1 gene or other causes.
The genes and proteins mentioned above all play a role in the regulation of a protein called bradykinin, which has been highlighted as a key protein in HAE attacks due to its ability to encourage swelling.Management of HAE typically involves treatment of sudden attacks and preventing attacks using treatments which effectively reduce or help to regulate the production and release of bradykinin.
The investigational medicinal product in this study, ISIS 721744, aims to reduce the production of bradykinin, a protein that, when active, increases and promotes swelling in the body. ISIS 721744 does this by indirectly reducing the amount of Kallikrein, one of the
proteins which eventually releases bradykinin from its inactive form and allows it to become active and encourage swelling.REC name
South Central - Hampshire A Research Ethics Committee
REC reference
22/SC/0235
Date of REC Opinion
2 Sep 2022
REC opinion
Further Information Favourable Opinion