Hereditary Angioedema (HAE)Phase 3NCT07298447
Donidalorsen Treatment in Children With Hereditary Angioedema
A Phase 3 study testing Donidalorsen in people with Hereditary Angioedema (HAE), run by Ionis Pharmaceuticals, Inc. at 16 sites in 5 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 2 to 11 years
- Conditions the study is for
- Hereditary Angioedema (HAE)
- What is being tested?
- Donidalorsen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 16 sitesin 5 countries
- Study dates
- 21 Apr 2026to Jun 2029
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 11 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Must be between the ages of 2 and less than 12 years, inclusive, at the time of informed consent and, as applicable, assent.
- Must weigh at least 9 kg at the time of informed consent and, as applicable, assent.
- Documented diagnosis of HAE-1/HAE-2 based upon both of the following:
- Documented clinical history consistent with HAE (SC or mucosal, non-pruritic swelling episodes without accompanying urticaria).
- 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.
Who cannot join
- Must not have any screening laboratory abnormalities or any other clinically significant abnormalities during screening that would render a participant unsuitable for inclusion.
- 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.
- 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/exclusion criteria may apply.
Trial locations and contacts
16 sites in 5 countries. Contact the study team or a site near you to ask about taking part.
16 sites in 5 countries
United States8 sites, 8 recruiting
- Recruiting
Ionis Investigative Site
Baton Rouge, Louisiana, 70809
- Recruiting
Ionis Investigative Site
Cincinnati, Ohio, 45236
- Recruiting
Ionis Investigative Site
Cleveland, Ohio, 44195
- Recruiting
Ionis Investigative Site
Hershey, Pennsylvania, 17033
- Recruiting
Ionis Investigative Site
Miami, Florida, 33136
- Recruiting
Ionis Investigative Site
Santa Monica, California, 90404
- Recruiting
Ionis Investigative Site
St Louis, Missouri, 63141
- Recruiting
Ionis Investigative Site
West Allis, Wisconsin, 53214
Italy4 sites, 4 recruiting
- Recruiting
Ionis Investigative Site
Milan, 20157
- Recruiting
Ionis Investigative Site
Padova, 35128
- Recruiting
Ionis Investigative Site
Roma, 00133
- Recruiting
Ionis Investigative Site
San Donato Milanese, 20097
Australia2 sites, 2 recruiting
- Recruiting
Ionis Investigative Site
Clayton, Victoria, 3168
- Recruiting
Ionis Investigative Site
South Brisbane, Queensland, 4101
About this study
Official title: An Open-Label Study of Donidalorsen in Pediatric Patients Age 2 to Less Than 12 Years Old With Hereditary Angioedema
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).
Read the 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.
- Conditions
- Hereditary Angioedema (HAE)
- Being tested
- Donidalorsen
- Medical subject headings
- Angioedemas, Hereditary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DonidalorsenDrug
Also called ISIS 721744, IONIS-PKK-LRx
Donidalorsen will be administered by subcutaneous (SC) injection.
| Study group | Role | What they receive |
|---|---|---|
| Donidalorsen: Group 1 | Experimental | Participant weighing 9 kilograms (kg) to less than (<)26 kg, will be administered donidalorsen over the period of one year. Receives: Drug: Donidalorsen |
| Donidalorsen: Group 2 | Experimental | Participant weighing greater than or equal to (≥)26 kg to <41 kg, will be administered donidalorsen over the period of one year. Receives: Drug: Donidalorsen |
| Donidalorsen: Group 3 | Experimental | Participant weighing ≥41kg, will receive donidalorsen over the period of one year. Receives: Drug: Donidalorsen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Treatment Emergent Adverse Events (TEAEs)
Measured: over the period of approximately 17 months
Maximum Plasma Concentration (Cmax) of Donidalorsen
Measured: over the period of approximately 17 months
Maximum Time to Reach Cmax (Tmax) of Donidalorsen
Measured: over the period of approximately 17 months
Trough Plasma Concentration (Ctrough) of Donidalorsen
Measured: over the period of approximately 17 months
Secondary outcomes (8)
Time-Normalized Number of Investigator-Confirmed HAE Attacks (per Month)
Measured: over the period of 12 months
Percentage of Investigator-Confirmed HAE Attack-free Participants
Measured: over the period of 12 months
Time-Normalized Number of Moderate or Severe Investigator-Confirmed HAE Attacks (per Month)
Measured: 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
Measured: over the period of 12 months
Time-Normalized Number of Investigator-Confirmed HAE Attacks Requiring Rescue Treatment
Measured: over the period of 12 months
Change From Baseline in Prekallikrein (PKK) Levels in Plasma
Measured: over the period of 12 months
Percent Change From Baseline in PKK Levels in Plasma
Measured: over the period of 12 months
Changes in Pediatrics Quality of Life (PedsQL) Scores for Participants
Measured: over the period of 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2025
- Study start21 Apr 2026
- Primary completionJun 2029 (estimated)
- Study completionJun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hereditary Angioedema (HAE)Studies of the same condition, open and under way.
- More trials run by Ionis Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ionis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07298447
- Sponsor's protocol ID
- ISIS 721744-CS8
- Other IDs
- U1111-1326-8613, 2025-523499-22-00, 2025
- Status last verified
- Sep 2026
- First submitted
- 19 Dec 2025
- Last updated
- 2 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Ionis may share anonymized individual participant data, aggregated clinical data, and other types of data that support the results in this study. Data requests from qualified researchers will be considered once all three of the following criteria are met: (1) 12 months from marketing approval of the study drug in both the United States and European Union; (2) 18 months from conclusion of the study; and (3) 6 months from publication of study article. Access would be via a secure environment and is contingent upon approval of a research proposal and entry into an appropriate data use agreement. Requests to access data can be submitted via the website https://vivli.org/ourmember/ionis/.
- Expanded access
- Available