This is a randomized, double-blind, Placebo controlled trial to evaluate the efficacy of ISIS 721744 in Patients with Hereditary Angioedema
- Conditions
- Hereditary AngioedemaMedDRA version: 20.0Level: PTClassification code 10019860Term: Hereditary angioedemaSystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Body processes [G] - Genetic Phenomena [G05]
- Registration Number
- EUCTR2019-001044-22-GB
- Lead Sponsor
- Ionis Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 24
1)Documented diagnosis of HAE-1/HAE-2 (for inclusion in Part A) or HAE-nC1-INH (for inclusion in Part B)
2)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. Complete the AAS questionnaire on a daily basis (minimum of 4 daily assessments per week) for the duration of the Screening Period.
3)Access to, and the ability to use, = 1 acute medication(s) to treat angioedema attacks
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 24
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1) Anticipated use of short-term prophylaxis for angioedema attacks for a pre-planned procedure during the screening or study periods
2) Concurrent diagnosis of any other type of recurrent angioedema, including acquired or idiopathic angioedema
3) History of acquired coagulopathies or bleeding diasthesis
4) Active infection with HIV, hepatitis C or hepatitis B diagnosed by initial serological testing and confirmed with RNA testing, or prior treatment for hepatitis C. Patients at Screening who test positive by serology, but negative by RNA may be allowed in consultation with the Sponsor Medical Monitor.
5) Patients with a history of acquired coagulopathies or bleeding diathesis (e.g. thrombocytopenia, disseminated intravascular coagulation, coagulopathy of liver disease, drug-induced platelet dysfunction, hyperfibrinolysis, acquired clotting factor inhibitors) and inherited bleeding disorders (e.g., hemophilia A, hemophilia B, other clotting
factor deficiencies, qualitative platelet disorders, inherited thrombocytopenia, vascular abnormalities).
6) Any clinically significant renal or hepatic diseases.
7) 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
8) Treatment with another investigational drug or biological agent within 1 month or 5 half-lives, whichever is longer, of screening
9) Exposure to any of the following medications:
-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
-Chronic prophylaxis with lanadelumab within 6 months prior to screening
-Oligonucleotides (including small interfering ribonucleic acid [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 clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: evaluate the clinical efficacy of antisense inhibitor of prekallikrein (IONIS PKK-LRx) in patients with hereditary angioedema (HAE) type 1 (HAE-1), HAE type 2 (HAE-2), or HAE with normal C1-inhibitor (C1-INH).;Secondary Objective: evaluate safety and tolerability of IONIS PKK-LRx in patients with HAE-1/HAE-2 or HAE with normal C1-INH (HAE-nC1-INH) and to evaluate the<br>effect of IONIS PKK-LRx on plasma prekallikrein (PKK) and other relevant biomarkers.;Primary end point(s): The primary endpoint is the time-normalized number of HAE attacks (per month) from Week 1 to Week 17.;Timepoint(s) of evaluation of this end point: HAE Attack Assessment will be evaluated from Week 1 to Week 17
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • The time-normalized number of HAE attacks (per month) from Week 5<br>to Week 17<br>• The time-normalized number of moderate or severe HAE attacks (per<br>month) from Week 5 to Week 17<br>• The number of patients with a clinical response (defined as a = 50%, =<br>70%, or = 90% reduction from Baseline in HAE attack<br>rate) by Week 17<br>• The number of HAE attacks requiring acute therapy from Week 5 to<br>Week 17<br>• cHK levels at Weeks 9 and 17<br>• PKK activity at Weeks 9 and 17<br>• Consumption of on-demand medication at Weeks 9 and 17<br>• AE-QoL questionnaire score at Weeks 9 and 17;Timepoint(s) of evaluation of this end point: HAE Attack Assessment will be evaluated from Week 5 to Week 17<br>cHK levels will be evaluated at Weeks 9 and 17<br>PKK activity will be evaluated at Weeks 9 and 17<br>Consumption of on-demand medication will be evaluated at Weeks 9 and 17<br>AE-QoL questionnaire score will be evaluated at Weeks 9 and 17