A Randomized, Double Blind, Placebo Controlled, Phase 2a Study to Assess the Clinical Efficacy of ISIS 721744, a Second Generation Ligand Conjugated Antisense Inhibitor of Prekallikrein, in Patients with Hereditary Angioedema
- Conditions
- HAEHereditary angioedema1000533010002426
- Registration Number
- NL-OMON49723
- Lead Sponsor
- Ionis Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 8
- Documented diagnosis of HAE-1/HAE-2 (for inclusion in Part A) or HAE-nC1-INH
(for inclusion in Part B);
- Participants must experience a minimum of 2 HAE attacks (assessed by the
Angioedema Activity Score [AAS] and confirmed by the investigator) during the
screening period;
- Access to, and the ability to use, 1 or more acute medication(s) to treat
angioedema attacks.
- Anticipated use of short-term prophylaxis for angioedema attacks for a
pre-planned procedure during the Screening or Study Periods.
- Concurrent diagnosis of any other type of recurrent angioedema, including
acquired or idiopathic angioedema.
- History of acquired coagulopathies or bleeding diathesis.
- Active infection with human immunodeficiency virus (HIV), hepatitis C or
chronic hepatitis B.
- Malignancy within 5 years, except for basal or squamous cell carcinoma of the
skin or carcinoma in situ of the cervix that has been successfully treated.
- Treatment with another investigational drug or biological agent within 1
month or 5 half-lives, whichever is longer, of Screening.
- 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 Lanadelumab within 10 weeks prior to Screening.
c. Oligonucleotides (including small interfering RNA) within 4 months of
Screening if single dose received, or within 12 months of Screening if multiple
doses received.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoint is the time-normalized number of HAE attacks (per month)<br /><br>from Week 1 to Week 17. </p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary endpoints include the following:<br /><br>* The time-normalized number of HAE attacks (per month) from Week 5 to Week 17<br /><br>* The time-normalized number of moderate or severe HAE attacks (per month) from<br /><br>Week 5 to Week 17<br /><br>* The number of patients with a clinical response (defined as a * 50%, * 70%,<br /><br>or * 90% reduction from Baseline in HAE attack rate) by Week 17<br /><br>* The number of HAE attacks requiring acute therapy from Week 5 to Week 17<br /><br>* Cleaved high molecular weight kininogen (cHK) levels at Weeks 9 and 17<br /><br>* PKK activity at Weeks 9 and 17<br /><br>* Consumption of on-demand medication at Weeks 9 and 17<br /><br>* Angioedema quality of life (AE-QoL) questionnaire score at Weeks 9 and 17 </p><br>