HAE Hereditary angioedema
Conditions
Interventions
Patients will receive either 6 (Cohort A) or 3 (Cohort B) doses, of either
study drug (80 mg per dose) or placebo as injection under the skin in either
their abdomen (stomach area), thigh or upper a
Sponsors
Ionis Pharmaceuticals, Inc.
Eligibility
Age
12 Years to 64 Years
Inclusion criteria
Inclusion criteria: • Patients must be aged >= 12 years at the time of informed consent, and, as applicable, assent • Patients must have a documented diagnosis of HAE-1/HAE-2 based upon ALL of the following: a. Documented clinical history consistent with HAE (subcutaneous [SC] or mucosal, non-pruritic swelling episodes without accompanying urticaria) b. Diagnostic testing results that confirm HAE-1/HAE-2: C1-INH functional level = 1 acute medication(s) (e.g., plasma derived or recombinant C1-INH concentrate or a BK2-receptor antagonist) to treat angioedema attacks
Exclusion criteria
Exclusion criteria: • Anticipated use of short-term prophylaxis for angioedema attacks for a pre-planned procedure during the Screening, Treatment or Post-Treatment Periods • Concurrent diagnosis of any other type of recurrent angioedema, including acquired, idiopathic angioedema or HAE with normal C1-INH (also known as HAE Type III) • Anticipated change in the use of concurrent androgen prophylaxis used to treat angioedema attacks • Participation in a prior ISIS 721744 study • Exposure to any of the following medications: a. Angiotensin-converting enzyme (ACE) inhibitors or any estrogen containing medications with systemic absorption (such as oral contraceptive or hormonal replacement therapy) within 4 weeks prior to Screening b. Chronic prophylaxis with Takhzyro (lanadelumab), Haegarda (C1-esterase inhibitor SQ), Cinryze and Ruconest (C1 esterase inhibitor) or Orladeyo (berotralstat) within 5 half lives prior to Screening (i.e., Takhzyro within 10 weeks prior to Screening, Haegarda/Cinryze/Ruconest within 2 weeks prior to screening, Orladeyo within 3 weeks prior to Screening) c. Oligonucleotides (including small interfering ribonucleic acid) within 4 months of Screening if single dose received, or within 12 months of Screening if multiple doses received. This exclusion does not apply to vaccines
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint is the time-normalized number of Investigator-confirmed HAE attacks (per month) from Week 1 to Week 25 compared to placebo. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints: • The time-normalized number of Investigator-confirmed HAE attacks (per month) from Week 5 to Week 25 compared to placebo • The percentage of Investigator-confirmed HAE attack-free patients from Week 5 to Week 25 compared to placebo • The time normalized number of moderate or severe Investigator-confirmed HAE attacks (per month) from Week 5 to Week 25 compared to placebo • The number of patients with a clinical response defined as a >= 50%, >= 70%, or >= 90% reduction from Baseline (i.e., screening rate) in Investigator-confirmed HAE attack rate between Week 5 to Week 25 compared to placebo • The number of Investigator-confirmed HAE attacks requiring acute HAE therapy from Week 5 to Week 25 compared to placebo • Percent of patients who are well controlled on the Angioedema Control Test (AECT) at Week 25 • Change in Angioedema Quality of Life (AE QoL) questionnaire total score at Week 25 Safety endpoints: The number, type, severity, and dose-relationship of AEs; vital signs; ECGs; and clinical laboratory parameters Exploratory endpoints include change or percent change from Baseline compared to placebo in the following: • PKK level in plasma • GAD-7 questionnaire score • EQ-5D-5L • PGIS • Work Productivity and Impairment (WPAI) questionnaire score Also: • Incidence of all cause emergency room visits, hospitalization and total inpatient days • PGIC • PK: Potential exposure response analysis using relevant exposure parameters (such as ISIS 721744 plasma Ctrough) and biomarkers (plasma PKK) and/or clinical endpoints, as appropriate | — |
Countries
Netherlands
Outcome results
None listed