A Phase 3 Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of ISIS 721744 in Patients with Hereditary Angioedema (HAE)
- Conditions
- Hereditary Angioedema (HAE)MedDRA version: 23.1Level: PTClassification code 10019860Term: Hereditary angioedemaSystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Body processes [G] - Genetic Phenomena [G05]
- Registration Number
- EUCTR2021-002571-19-PL
- Lead Sponsor
- Ionis Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 84
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 < 40% normal level. Patients with a functional level of 40% to 50% of normal can be enrolled if their complement factor C4 level is below the lower limit of normal (LLN) or if a known pathogenic mutation in the SERPING1 gene has been demonstrated
c. At least 1 of the following: age at reported HAE onset = 30 years; a family history consistent with HAE-1/HAE-2; or complement component 1q within the normal range
Patients must:
a. Experience a minimum of 2 HAE attacks (confirmed by the Investigator) during the Screening Period
b. Be willing to complete the PRO assessments throughout the study
Patients must have access to, and the ability to use, = 1 acute medication(s) (e.g., plasma-derived or recombinant C1-INH concentrate or a BK2-receptor antagonist) to treat angioedema attacks
Are the trial subjects under 18? yes
Number of subjects for this age range: 10
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 69
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5
• 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, Haegarda, Cinryze or Orladeyo within 5 half-lives prior to Screening (i.e., Takhzyro within 10 weeks prior to Screening, Haegarda/Cinryze 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of the study is to evaluate the clinical efficacy of ISIS 721744 in patients with HAE.;Secondary Objective: Evaluate the effects of ISIS 721744 on the quality and pattern of HAE attacks and their impact on Quality of Life.;Primary end point(s): The primary endpoint is the time-normalized number of Investigator-confirmed HAE attacks (per month) from Week 1 to Week 25 compared to placebo. ;Timepoint(s) of evaluation of this end point: Timepoints are described within the text in section E.5.1
- Secondary Outcome Measures
Name Time Method Secondary end point(s): The time-normalized number of Investigator-confirmed HAE attacks (per month) from Week 5 to Week 25 compared to placebo<br>• The percentage of Investigator-confirmed HAE attack-free patients from Week 5 to Week 25 compared to placebo<br>• The time-normalized number of moderate or severe Investigator-confirmed HAE attacks (per month) from Week 5 to Week 25 compared to placebo<br>• 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<br>• Percent of patients who are well-controlled based on the AECT at Week 25<br>• Change in AE-QoL questionnaire total score at Week 25 <br>• The number of Investigator-confirmed HAE attacks requiring acute therapy from Week 5 to Week 25 compared to placebo. ;Timepoint(s) of evaluation of this end point: Timepoints are described within the text in section E.5.2