Donidalorsen Treatment in Children with Hereditary Angioedema

Start 1 Apr 2026 · Status Ongoing, recruiting · 3 EU/EEA countries · 8 sites · Protocol ISIS 721744-CS8

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)

Status Ongoing, recruiting

Participants planned 20

Countries 3

Sites 8

Hereditary Angioedema (HAE)

Evaluate the safety, tolerability and pharmacokinetics of donidalorsen in pediatric participants with HAE

Key facts

Sponsor: Ionis Pharmaceuticals Inc.
Participant type: Pediatric, Patients
Age range: 0-17 years
Gender: Male and Female
Therapeutic area: Phenomena and Processes [G] - Genetic Phenomena [G05], Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
Trial duration: 1 Apr 2026 → ongoing
Decision date (initial): 2026-02-25
Transition trial: No
Low-intervention: No
Rare-disease indication: Yes
Vulnerable population: Yes
Funding sources: Ionis Pharmaceuticals, Inc.

External identifiers

EU CT number: 2025-523499-22-00
WHO UTN: U1111-1326-8613

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Prophylaxis, Therapy, Pharmacokinetic, Pharmacodynamic

Evaluate the safety, tolerability and pharmacokinetics of donidalorsen in pediatric participants with HAE

Secondary objectives 3

1. Evaluate the efficacy of dosing with donidalorsen in pediatric participants with HAE
2. Assess prekallikrein (PKK) levels in plasma (pharmacodynamics)
3. Assess the impact of treatment on the participant’s quality of life

Conditions and MedDRA coding

Hereditary Angioedema (HAE)

Version	Level	Code	Term	System organ class
27.1	PT	10019860	Hereditary angioedema	100000004850

Regulatory references

Scientific advice from competent authorities: European Medicines Agency
EMA paediatric investigation plan (PIP): EMEA-003112-PIP01-21
Plan to share 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/

EU CT number	Title	Sponsor
2023-509201-77-00	An Open-Label, Long Term Safety and Efficacy Study of Donidalorsen in the Prophylactic Treatment of Hereditary Angioedema (HAE).	Ionis Pharmaceuticals Inc.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

3. Must be between the ages of 2 and less than 12 years, inclusive, at the time of informed consent and, as applicable, assent.
4. Must weigh at least 9 kg at the time of informed consent and, as applicable, assent.
6. Documented diagnosis of HAE-1/HAE-2 based upon both of the following: a. Documented clinical history consistent with HAE b. Diagnostic testing results that confirm HAE-1/HAE-2

Exclusion criteria 3

2. Must not have any screening laboratory abnormalities or any other clinically significant abnormalities during screening that would render a participant unsuitable for inclusion
12. Concurrent diagnosis of any other type of recurrent angioedema, including idiopathic angioedema or HAE with normal C1-INH (HAE-nC1-INH or Type III).
8. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Incidence and severity of treatment-emergent adverse events (TEAEs)
2. Plasma pharmacokinetics and concentrations of donidalorsen

Secondary endpoints 7

1. The time-normalized number of investigator-confirmed HAE attacks (per month) over the period of 12 months.
3. The percentage of investigator-confirmed HAE attack-free participants over the period of 12 months.
4. The time-normalized number of moderate or severe investigatorconfirmed HAE attacks (per month) over the period of 12 months.
5. The number of participants with a clinical response defined as a ≥ 50%, ≥ 70%, or ≥ 90% reduction from Baseline in investigator-confirmed HAE attack rate over the period of 12 months.
6. The number of investigator-confirmed HAE attacks requiring rescue treatment (i.e., acute therapy) over the period of 12 months.
7. Change in PKK levels in plasma over the period of 12 months.
8. Changes in Pediatrics Quality of Life (PedsQL) scores for participants over the period of 12 months.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Isis 721744

PRD12909821 · Product

Active substance: Donidalorsen
Substance synonyms: ISIS 721744, GalNAc-conjugated 2'-MOE ASO targeting PKK mRNA, Synthetic 2'-O-(2-methoxy ethyl)-modified antisense oligonucleotide linked to a triantennary cluster of N-acetyl galactosamine sugars targeting prekallikrein mRNA, IONIS-PKK-LRx, 5'-O-(6-{5-N-[tris({6-[(2-acetamido-2-deoxy-β-D-galactopyranosyl)oxy]-hexylamino}-3-oxopropoxymethyl)methyl]amino-5-oxopentanoyl}aminohexyl-1-phosphatyl)-2'-O-(2-methoxyethyl)-5-methyl-Pthiouridylyl-(3'-O->5'-O)-2'-O-(2-methoxyethyl)-P-thioguanylyl-(3'-O->5'-O)-2'-O-(2-methoxyethyl)-5-methylcytidylyl-(3'-O->5'-O)-2'-O-(2-methoxyethyl)adenylyl-(3'-O->5'-O)-2'-O-(2-methoxyethyl)-P-thioadenylyl-(3'-O->5'-O)-2'-deoxy-P-thioguanylyl -(3'-O->5'-O)-P-thiothymidylyl-(3'-O->5'-O)-2'- deoxy-5-methyl-P-thiocytidylyl-(3'-O->5'-O)-P-thiothymidylyl-(3'-O->5'-O)-2'- deoxy-5-methyl-P-thiocytidylyl-(3'-O->5'-O)-Pthiothymidylyl-(3'-O->5'-O)-P-thiothymidylyl-(3'-O->5'-O)-2'-deoxy-Pthioguanylyl-(3'-O->5'-O)-2'-deoxy-P-thioguanylyl -(3'-O->5'-O)-2'- deoxy-5-methyl-P-thiocytidylyl-(3'-O->5'-O)-2'-O-(2-methoxyethyl)adenylyl-(3'-O->5'-O)-2'-O-(2-methoxyethyl)adenylyl-(3'-O->5'-O)-2'-O-(2-methoxyethyl)-P-thioadenylyl-(3'-O->5'-O)-2'-O-(2-methoxyethyl)-5-methyl-P-thiocytidylyl-(3'-O->5'-O)-2'-O-(2-methoxyethyl)-adenosine, N-acetyl galactosamine conjugated 2'-MOE ASO targeting prekallikrein mRNA
Pharmaceutical form: INJECTION
Route of administration: SUBCUTANEOUS
Max daily dose: 00 mg milligram(s)
Max total dose: 00 mg milligram(s)
Max treatment duration: 1 Week(s)
Authorisation status: Not Authorised
MA holder: IONIS PHARMACEUTICALS, INC.
Paediatric formulation: Yes
Orphan designation: Yes
Orphan designation number: EMA/OD/0000156328

Isis 721744

PRD9568286 · Product

Active substance: Donidalorsen
Pharmaceutical form: INJECTION
Route of administration: SUBCUTANEOUS
Max daily dose: 00 mg milligram(s)
Max total dose: 00 mg milligram(s)
Max treatment duration: 1 Week(s)
Authorisation status: Not Authorised
MA holder: IONIS PHARMACEUTICALS, INC.
Paediatric formulation: No
Orphan designation: Yes
Orphan designation number: EMA/OD/0000156328

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ionis Pharmaceuticals Inc.

Sponsor organisation: Ionis Pharmaceuticals Inc.
Address: 2855 Gazelle Court
City: Carlsbad
Postcode: 92010-6670
Country: United States

Scientific contact point

Organisation: Ionis Pharmaceuticals Inc.
Contact name: Global Regulatory Affairs

Public contact point

Organisation: Ionis Pharmaceuticals Inc.
Contact name: Global Regulatory Affairs

Third parties 3

Organisation	City, country	Duties
Cognizant Worldwide Limited ORG-100042036	London, United Kingdom	Code 8
Medpace Finland Oy ORG-100009147	Helsinki, Finland	On site monitoring, Code 10, Code 12, Code 2, Laboratory analysis, Data management, Code 8
Xerimis B.V. ORG-100033795	Rozenburg Nh, Netherlands	Code 14

Locations

3 EU/EEA countries · 8 investigational sites

By country

Country	MS status	Planned subjects	Sites
Italy	Ongoing, recruiting	4	4
Poland	Authorised, recruiting	2	2
Spain	Authorised, recruiting	2	2
Rest of world Canada, United States	—	12	—

Investigational sites

Italy

4 sites · Ongoing, recruiting

Policlinico San Donato S.p.A.

UO Medicina, Piazza Edmondo Malan 2, 20097, San Donato Milanese

Azienda Ospedaliera Policlinico Universitario Tor Vergata

Centro di RIferimento Malattie Reumatologiche ed Immunologiche Rare, Viale Oxford 81, 00133, Rome

ASST Fatebenefratelli Sacco

Medicina Interna, Via Giovanni Battista Grassi 74, 20157, Milan

Azienda Ospedaliera di Padova

UOSD Allergologia, Via Nicolo' Giustiniani 2, 35128, Padova

Poland

2 sites · Authorised, recruiting

Medical Network Sp. z o.o.

WIP Warsaw IBD Point Profesor Kierkuś, Ul. Plowiecka 103, 04-501, Warsaw

Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwersytecki W Krakowie

Centrum Alergologii - Poradnia Alergologiczna, Ul. Botaniczna 3, 31-503, Cracow

Spain

2 sites · Authorised, recruiting

Hospital Universitario La Paz

Alergology, Paseo De La Castellana 261, 28046, Madrid

Hospital Universitari Vall D Hebron

Alergology, Passeig De La Vall D'Hebron 119-129, 08035, Barcelona

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country	Trial start	Recruitment start
Italy	2026-04-13	2026-04-21
Poland	2026-04-24
Spain	2026-04-01

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 23 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Type	Title	Version
Protocol (for publication)	D1_Protocol_2025-523499-22-00_Ionis_redacted	1
Protocol (for publication)	D4_Patient facing documents_ Licensing document_Ionis	1.0
Recruitment arrangements (for publication)	K1_Recruitment arrangements_ES_Ionis	1.0
Recruitment arrangements (for publication)	K1_Recruitment arrangements_IT_Ionis	1.0
Recruitment arrangements (for publication)	K1_Recruitment arrangements_PL_Ionis	1.0
Recruitment arrangements (for publication)	K2_Recruitment material_Brochure_Ionis	1
Recruitment arrangements (for publication)	K2_Recruitment material_Brochure_Ionis	1
Recruitment arrangements (for publication)	K2_Recruitment material_Brochure_Ionis	1
Subject information and informed consent form (for publication)	L1_SIS and ICF_ ParentalGuardian ICF_Ionis_redacted	1.0
Subject information and informed consent form (for publication)	L1_SIS and ICF_ YoungParticipantInfo_Ionis_redacted	1.0
Subject information and informed consent form (for publication)	L1_SIS and ICF_Assent form_Ionis _redacted	1.0
Subject information and informed consent form (for publication)	L1_SIS and ICF_Assent_Ionis_redacted	1.0
Subject information and informed consent form (for publication)	L1_SIS and ICF_Data Protection Form_Ionis	1.0
Subject information and informed consent form (for publication)	L1_SIS and ICF_Minor Information Sheet_Ionis_redacted	1.0
Subject information and informed consent form (for publication)	L1_SIS and ICF_Parental ICF_Ionis _redacted	1.0
Subject information and informed consent form (for publication)	L1_SIS and ICF_Parental ICF_Ionis_redacted	1.0
Subject information and informed consent form (for publication)	L2_Other subject information material_PDA_ Ionis	1
Subject information and informed consent form (for publication)	L2_Other subject information material_PDA_Ionis	1
Subject information and informed consent form (for publication)	L2_Other subject information material_PECard_Ionis	1
Synopsis of the protocol (for publication)	D1_Protocol synopsis_EN_2025-523499-22-00_Ionis_redacted	1
Synopsis of the protocol (for publication)	D1_Protocol synopsis_ES_2025-523499-22-00_Ionis_redacted	1
Synopsis of the protocol (for publication)	D1_Protocol synopsis_IT_2025-523499-22-00_Ionis_redacted	1
Synopsis of the protocol (for publication)	D1_Protocol synopsis_PL_2025-523499-22-00_Ionis_redacted	1

Application history

2 submissions — initial application plus substantial / non-substantial modifications

#	Type	Code	Submitted	Reference MS	Conclusion	Decision date
1	INITIAL	IN	2025-11-05	Poland	Acceptable 2026-02-23	2026-02-25
2	SUBSTANTIAL MODIFICATION	SM-1	2026-04-21		Acceptable	2026-05-05