Donidalorsen Treatment in Children With Hereditary Angioedema

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: Recruiting
• Conditions: Hereditary Angioedema (HAE)
• Intervention / Treatment: Drug: Donidalorsen

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: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

• Study Contact: Name: Ionis Pharmaceuticals, Inc.; Phone Number: (844) 201-3192; Email: IonisDonidalorsenPediatric@clinicaltrialmedia.com

Study Locations

• Italy
  • Milan, Italy, 20157
    • Recruiting
    • Ionis Investigative Site
  • Padova, Italy, 35128
    • 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
  • Missouri
    • St Louis, Missouri, United States, 63141
      • Recruiting
      • Ionis Investigative Site
  • Ohio
    • Cincinnati, Ohio, United States, 45236
      • Recruiting
      • Ionis Investigative Site
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Recruiting
      • Ionis Investigative Site

Participation Criteria

Eligibility Criteria

• 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

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

Outcome 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 Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Ionis Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: December 19, 2025
• First Submitted That Met QC Criteria: December 19, 2025
• First Posted (Actual): December 23, 2025

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immunologic Deficiency Syndromes; Skin Diseases; Urticaria; Skin Diseases, Vascular; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin and Connective Tissue Diseases; Angioedema; Angioedemas, Hereditary; donidalorsen; IONIS-PKK-LRx
• Other Study ID Numbers: ISIS 721744-CS8; 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