NCT04307381

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of extended dosing of donidalorsen administered subcutaneously (SC), with alternative dosing and/or dose frequency with donidalorsen in participants with hereditary angioedema (HAE).

Trial Health

90
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_2

Timeline
Completed

Started Apr 2020

Longer than P75 for phase_2

Geographic Reach
2 countries

7 active sites

Status
completed

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

March 11, 2020

Completed
2 days until next milestone

First Posted

Study publicly available on registry

March 13, 2020

Completed
19 days until next milestone

Study Start

First participant enrolled

April 1, 2020

Completed
4.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 24, 2025

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 24, 2025

Completed
Last Updated

March 24, 2025

Status Verified

March 1, 2025

Enrollment Period

4.8 years

First QC Date

March 11, 2020

Last Update Submit

March 21, 2025

Conditions

Keywords

Hereditary AngioedemaHAE

Outcome Measures

Primary Outcomes (1)

  • Percentage of Participants with at Least One Treatment-emergent Adverse Event (TEAE), Graded by Severity

    Up to Week 221

Secondary Outcomes (4)

  • The Time-normalized HAE Attacks (per Month) by Treatment

    Up to Week 221

  • Plasma Prekallikrein (PKK) Levels

    Up to Week 221

  • Consumption of On-demand Medications

    Up to Week 221

  • Angioedema Quality of Life (AE-QoL) Questionnaire Score

    Up to Week 221

Study Arms (1)

Donidalorsen

EXPERIMENTAL

Participants will be administered donidalorsen SC for up to 53 weeks. Participants will also be administered donidalorsen in the extended treatment period for an additional 156 weeks, up to week 209.

Drug: Donidalorsen

Interventions

Donidalorsen administered SC

Also known as: ISIS 721744, IONIS-PKK-LRx
Donidalorsen

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Satisfactory completion of ISIS 721744-CS2 (index study) through Week 17 with an acceptable safety and tolerability profile, per Sponsor and Investigator judgement
  • Able and willing to participate in a 64-week study
  • Females must be non-pregnant, non-lactating and either surgically sterile or post-menopausal
  • Males must be surgically sterile or abstinent\* or if engaged in sexual relations with a female of child-bearing potential, participant is utilizing an acceptable contraceptive method
  • Participants must have access to, and the ability to use, ≥ 1 acute medication(s) (e.g., plasma-derived or recombinant C1- inhibitor (C1-INH) concentrate or a bradykinin-2 \[BK-2\] antagonist) to treat angioedema attacks

You may not qualify if:

  • \. Have any new condition or worsening of an existing condition or change or anticipated change in medication, which in the opinion of the Investigator would make the participant unsuitable for enrollment, or could interfere with the participant participating in or completing the study

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (7)

Ionis Investigative Site

Scottsdale, Arizona, 85251, United States

Location

Ionis Investigative Site

Santa Monica, California, 90404, United States

Location

Ionis Investigative Site

Plymouth, Minnesota, 55446, United States

Location

Ionis Investigative Site

Cincinnati, Ohio, 45231, United States

Location

Ionis Investigative Site

Hershey, Pennsylvania, 17033, United States

Location

Ionis Investigative Site

Dallas, Texas, 75231, United States

Location

Ionis Investigative Site

Amsterdam, 1105 AZ, Netherlands

Location

Related Publications (1)

  • Petersen RS, Bordone L, Riedl MA, Tachdjian R, Craig TJ, Lumry WR, Manning ME, Bernstein JA, Raasch J, Zuraw BL, Deng Y, Newman KB, Alexander VJ, Lui C, Schneider E, Cohn DM. A phase 2 open-label extension study of prekallikrein inhibition with donidalorsen for hereditary angioedema. Allergy. 2024 Mar;79(3):724-734. doi: 10.1111/all.15948. Epub 2023 Nov 27.

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

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR
Expanded Access
Yes

Study Record Dates

First Submitted

March 11, 2020

First Posted

March 13, 2020

Study Start

April 1, 2020

Primary Completion

January 24, 2025

Study Completion

January 24, 2025

Last Updated

March 24, 2025

Record last verified: 2025-03

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