A Phase 3 Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of ISIS 721744 in Patients with Hereditary Angioedema (HAE)

HAE is a rare and potentially life-threatening genetic disease that causes painful swelling attacks in various parts of the body, mainly in the hands, feet, face, throat, and stomach area. Swelling in the airway can restrict breathing and be fatal. A HAE attack may be triggered by emotional trauma or stress; however, an attack often occurs without a known trigger. Attacks can occur without warning and last up to several days if untreated.

The study drug is called donidalorsen (don-id-a-lor-sen) and it is being studied as a potential prophylactic treatment for HAE. Donidalorsen is an antisense therapy, and is designed to lower the amount of a protein called prekallikrein (PKK) in the body. PKK is made in the liver and when released into the blood stream can cause HAE attacks. By lowering PKK, donidalorsen may help reduce or prevent HAE attacks. Donidalorsen is a small volume injection that is administered with an ultrafine needle just under the skin of the upper arm, abdomen, or thigh every 4 weeks or every 8 weeks.

Donidalorsen is an antisense therapy that is being research by Ionis Pharmaceuticals, Inc., the sponsor of the study, as a new potential treatment for HAE. Antisense therapies change the process of producing a protein before it even begins. To build a protein, a cell must make a copy of the DNA, which contains specific instructions for how to make that particular protein. This copy, called messenger RNA (mRNA), carries the instructions to the part of the cell where proteins are made.

Antisense therapies are designed to seek out, bind to and destroy a mRNA in a highly specific manner, so that the amount of disease-causing protein is dramatically decreased.

To learn more about lonis’s antisense technology please visit https://www.ionispharma.com/ionis-innovation/antisense-technology/.

You may qualify for the study if you meet the following requirements:

• You are 12 years of age or older.
• You have been diagnosed with HAE.
• You have access to at least 1 acute medication to treat HAE attacks.

Other requirements will apply.

• The study will last up to 46 weeks (almost a year) in total.
• Participants will receive an injection every 4 or 8 weeks.
• Participants will receive study health assessments, complete a daily diary, and be monitored by the study healthcare team.
• Many study visits can be done in the home through home healthcare services.

At the beginning of the study, participants will be divided randomly into two groups. During the first 25 weeks of the study, one group will receive donidalorsen injections and the other group will receive placebo injections. Participants are twice as likely to receive donidalorsen than placebo.

Including the Screening Period, the OASIS-HAE study lasts 46 weeks (a little less than a year). Following the end of the 25-week (almost 6 month) treatment period, participants may be eligible to participate in an open-label extension study where all participants receive donidalorsen.

Before starting the study, participants must sign the Informed Consent Form and/or the Assent Form. Participants will then receive health assess­ments to confirm they qualify for the study. This is called the Screening Period. This period may last up to 8 weeks but could be less.

There may be compensation for the time you spend taking part in the study. You may also be able to have some of your travel costs for taking part in the study paid back, like mileage and lodging. Please ask someone from the study staff for more information.

There is no cost associated with participation in this study. Travel expenses (such as transportation and hotel, if required) will be provided. You may also be reimbursed for certain travel expenses that are related to your study visits (such as meals, parking, and taxi fares).