Hereditary Angioedema (HAE)
Conditions
Brief summary
The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of donidalorsen in pediatric participants with hereditary angioedema (HAE) Type I (HAE-1) or Type II (HAE-2).
Detailed description
This is an open-label study to evaluate the safety, efficacy, and pharmacokinetics (PK) and pharmacodynamics (PD) of donidalorsen in pediatric participants age 2 to less than 12 years old with HAE Type I (HAE-1) or Type II (HAE-2). The study consists of 3 parts: 1) a 3-month Screening Period, 2) a one-year Treatment Period, and 3) a 3-month Post-Treatment Period.
Interventions
DRUGDonidalorsen
Donidalorsen will be administered by subcutaneous (SC) injection.
Sponsors
Ionis Pharmaceuticals, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Must be between the ages of 2 and less than 12 years, inclusive, at the time of informed consent and, as applicable, assent. 2. Must weigh at least 9 kg at the time of informed consent and, as applicable, assent. 3. Documented diagnosis of HAE-1/HAE-2 based upon both of the following: 1. Documented clinical history consistent with HAE (SC or mucosal, non-pruritic swelling episodes without accompanying urticaria). 2. Diagnostic testing results that confirm HAE-1/HAE-2: C1-inhibitor (C1-INH) functional level \<50% normal level AND complement factor C4 level below the lower limit of normal (LLN); OR a known pathogenic mutation in the SERPING1 gene. Key
Exclusion criteria
1. Must not have any screening laboratory abnormalities or any other clinically significant abnormalities during screening that would render a participant unsuitable for inclusion. 2. Must not have been treated with another investigational drug, biological agent, or device within 1 month of Screening, or 5 half-lives of investigational agent, whichever is longer. 3. Concurrent diagnosis of any other type of recurrent angioedema, including idiopathic angioedema or HAE with normal C1-INH (HAE-nC1-INH or Type III). Note: Other protocol-specified inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants with Treatment Emergent Adverse Events (TEAEs) | over the period of approximately 17 months |
| Maximum Plasma Concentration (Cmax) of Donidalorsen | over the period of approximately 17 months |
| Maximum Time to Reach Cmax (Tmax) of Donidalorsen | over the period of approximately 17 months |
| Trough Plasma Concentration (Ctrough) of Donidalorsen | over the period of approximately 17 months |
Secondary
| Measure | Time frame |
|---|---|
| Time-Normalized Number of Investigator-Confirmed HAE Attacks (per Month) | over the period of 12 months |
| Percentage of Investigator-Confirmed HAE Attack-free Participants | over the period of 12 months |
| Time-Normalized Number of Moderate or Severe Investigator-Confirmed HAE Attacks (per Month) | over the period of 12 months |
| Number of Participants with a Clinical Response Defined as a ≥ 50 Percent (%), ≥ 70% and ≥ 90% Reduction from Baseline in Investigator-Confirmed HAE Attack Rate | over the period of 12 months |
| Time-Normalized Number of Investigator-Confirmed HAE Attacks Requiring Rescue Treatment | over the period of 12 months |
| Change From Baseline in Prekallikrein (PKK) Levels in Plasma | over the period of 12 months |
| Percent Change From Baseline in PKK Levels in Plasma | over the period of 12 months |
| Changes in Pediatrics Quality of Life (PedsQL) Scores for Participants | over the period of 12 months |
Countries
Australia, Italy, Poland, Spain, United States
Contacts
CONTACTIonis Pharmaceuticals, Inc.
Outcome results
None listed