NCT07298447

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).

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
20

participants targeted

Target at below P25 for phase_3

Timeline
36mo left

Started Jul 2026

Typical duration for phase_3

Geographic Reach
4 countries

6 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 19, 2025

Completed
4 days until next milestone

First Posted

Study publicly available on registry

December 23, 2025

Completed
6 months until next milestone

Study Start

First participant enrolled

July 1, 2026

Expected
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2029

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2029

Last Updated

April 29, 2026

Status Verified

April 1, 2026

Enrollment Period

2.9 years

First QC Date

December 19, 2025

Last Update Submit

April 27, 2026

Conditions

Outcome Measures

Primary Outcomes (4)

  • 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 Outcomes (8)

  • 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

  • +3 more secondary outcomes

Study Arms (3)

Donidalorsen: Group 1

EXPERIMENTAL

Participant weighing 9 kilograms (kg) to less than (\<)26 kg, will be administered donidalorsen over the period of one year.

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.

Drug: Donidalorsen

Donidalorsen: Group 3

EXPERIMENTAL

Participant weighing ≥41kg, will receive donidalorsen over the period of one year.

Drug: Donidalorsen

Interventions

Donidalorsen will be administered by subcutaneous (SC) injection.

Also known as: ISIS 721744, IONIS-PKK-LRx
Donidalorsen: Group 1Donidalorsen: Group 2Donidalorsen: Group 3

Eligibility Criteria

Age2 Years - 11 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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.

You may not qualify if:

  • 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).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

Ionis Investigative Site

Santa Monica, California, 90404, United States

RECRUITING

Ionis Investigative Site

St Louis, Missouri, 63141, United States

RECRUITING

Ionis Investigative Site

Cincinnati, Ohio, 45236, United States

RECRUITING

Ionis Investigative Site

Milan, 20157, Italy

RECRUITING

Ionis Investigative Site

Warsaw, 04-501, Poland

RECRUITING

Ionis Investigative Site

Barcelona, 08035, Spain

RECRUITING

MeSH Terms

Conditions

Angioedemas, Hereditary

Interventions

donidalorsenIONIS-PKK-LRx

Condition Hierarchy (Ancestors)

AngioedemaVascular DiseasesCardiovascular DiseasesHereditary Complement Deficiency DiseasesPrimary Immunodeficiency DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesUrticariaSkin Diseases, VascularSkin DiseasesSkin and Connective Tissue DiseasesHypersensitivity, ImmediateHypersensitivityImmune System DiseasesImmunologic Deficiency Syndromes

Central Study Contacts

Study Design

Study Type
interventional
Phase
phase 3
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR
Expanded Access
Yes

Study Record Dates

First Submitted

December 19, 2025

First Posted

December 23, 2025

Study Start (Estimated)

July 1, 2026

Primary Completion (Estimated)

June 1, 2029

Study Completion (Estimated)

June 1, 2029

Last Updated

April 29, 2026

Record last verified: 2026-04

Data Sharing

IPD Sharing
Will share

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/.

More information

Locations