Donidalorsen Treatment in Children With Hereditary Angioedema

September 1, 2026 updated by: Ionis Pharmaceuticals, Inc.

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Expanded Access

Expanded Access

A way for patients with serious diseases or conditions who cannot participate in a clinical trial to gain access to a medical product that has not been approved by the U.S. Food and Drug Administration (FDA). Also called compassionate use. There are different expanded access types.
Available

Available

  • Available: Expanded access is currently available for this investigational treatment, and patients who are not participants in the clinical study may be able to gain access to the drug, biologic, or medical device being studied.
  • No longer available: Expanded access was available for this intervention previously but is not currently available and will not be available in the future.
  • Temporarily not available: Expanded access is not currently available for this intervention but is expected to be available in the future.
  • Approved for marketing: The intervention has been approved by the U.S. Food and Drug Administration for use by the public.
 outside the clinical trial. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Australia
    • Queensland
      • South Brisbane, Queensland, Australia, 4101
        • Recruiting
        • Ionis Investigative Site
    • Victoria
      • Clayton, Victoria, Australia, 3168
        • Recruiting
        • Ionis Investigative Site
  • Italy
      • Milan, Italy, 20157
        • Recruiting
        • Ionis Investigative Site
      • Padova, Italy, 35128
        • Recruiting
        • Ionis Investigative Site
      • Roma, Italy, 00133
        • Recruiting
        • Ionis Investigative Site
      • San Donato Milanese, Italy, 20097
        • Recruiting
        • Ionis Investigative Site
  • Poland
      • Warsaw, Poland, 04-501
        • Recruiting
        • Ionis Investigative Site
  • Spain
      • Barcelona, Spain, 08035
        • Recruiting
        • Ionis Investigative Site
  • United States
    • California
      • Santa Monica, California, United States, 90404
        • Recruiting
        • Ionis Investigative Site
    • Florida
      • Miami, Florida, United States, 33136
        • Recruiting
        • Ionis Investigative Site
    • Louisiana
      • Baton Rouge, Louisiana, United States, 70809
        • Recruiting
        • Ionis Investigative Site
    • Missouri
      • St Louis, Missouri, United States, 63141
        • Recruiting
        • Ionis Investigative Site
    • Ohio
      • Cincinnati, Ohio, United States, 45236
        • Recruiting
        • Ionis Investigative Site
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Ionis Investigative Site
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Recruiting
        • Ionis Investigative Site
    • Wisconsin
      • West Allis, Wisconsin, United States, 53214
        • Recruiting
        • Ionis Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Description

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/exclusion criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Donidalorsen: Group 1
Participant weighing 9 kilograms (kg) to less than (<)26 kg, will be administered donidalorsen over the period of one year.
Drug: Donidalorsen
Donidalorsen will be administered by subcutaneous (SC) injection.
Other Names:
  • ISIS 721744
  • IONIS-PKK-LRx
Experimental: Donidalorsen: Group 2
Participant weighing greater than or equal to (≥)26 kg to <41 kg, will be administered donidalorsen over the period of one year.
Drug: Donidalorsen
Donidalorsen will be administered by subcutaneous (SC) injection.
Other Names:
  • ISIS 721744
  • IONIS-PKK-LRx
Experimental: Donidalorsen: Group 3
Participant weighing ≥41kg, will receive donidalorsen over the period of one year.
Drug: Donidalorsen
Donidalorsen will be administered by subcutaneous (SC) injection.
Other Names:
  • ISIS 721744
  • IONIS-PKK-LRx

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Number of Participants with Treatment Emergent Adverse Events (TEAEs)
Time Frame: over the period of approximately 17 months
over the period of approximately 17 months
Maximum Plasma Concentration (Cmax) of Donidalorsen
Time Frame: over the period of approximately 17 months
over the period of approximately 17 months
Maximum Time to Reach Cmax (Tmax) of Donidalorsen
Time Frame: over the period of approximately 17 months
over the period of approximately 17 months
Trough Plasma Concentration (Ctrough) of Donidalorsen
Time Frame: over the period of approximately 17 months
over the period of approximately 17 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Time-Normalized Number of Investigator-Confirmed HAE Attacks (per Month)
Time Frame: over the period of 12 months
over the period of 12 months
Percentage of Investigator-Confirmed HAE Attack-free Participants
Time Frame: over the period of 12 months
over the period of 12 months
Time-Normalized Number of Moderate or Severe Investigator-Confirmed HAE Attacks (per Month)
Time Frame: over the period of 12 months
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
Time Frame: over the period of 12 months
over the period of 12 months
Time-Normalized Number of Investigator-Confirmed HAE Attacks Requiring Rescue Treatment
Time Frame: over the period of 12 months
over the period of 12 months
Change From Baseline in Prekallikrein (PKK) Levels in Plasma
Time Frame: over the period of 12 months
over the period of 12 months
Percent Change From Baseline in PKK Levels in Plasma
Time Frame: over the period of 12 months
over the period of 12 months
Changes in Pediatrics Quality of Life (PedsQL) Scores for Participants
Time Frame: over the period of 12 months
over the period of 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ionis Pharmaceuticals, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 21, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 19, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 19, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 23, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 2, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 1, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ISIS 721744-CS8
  • 2025 (U.S. NIH Grant/Contract: Faculty of Social Sciences Scientific Grant at the University of Gdańsk)
  • U1111-1326-8613 (Other Identifier: WHO Universal Trial Number (UTN))
  • 2025-523499-22-00 (Other Identifier: EU Trial No.)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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/.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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