Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ended
Participants planned
20
Countries
1
Sites
1
Hereditary Angioedema
To evaluate the safety of extended dosing, and alternative dosing and/or dose frequency with ISIS 721744 in patients with HAE
Key facts
- Sponsor
- Ionis Pharmaceuticals Inc.
- Participant type
- Patients
- Age range
- 18-64 years
- Gender
- Male and Female
- Therapeutic area
- Phenomena and Processes [G] - Genetic Phenomena [G05]
- Trial duration
- 22 Oct 2020 → 24 Jan 2025
- Decision date (initial)
- 2024-11-04
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- No
- Funding sources
- Ionis Pharmaceuticals, Inc
External identifiers
- EU CT number
- 2024-517249-15-00
- EudraCT number
- 2020-000197-14
- WHO UTN
- U1111-1311-8916
- ClinicalTrials.gov
- NCT04307381
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Pharmacodynamic, Pharmacokinetic, Others, Therapy, Safety, Efficacy
To evaluate the safety of extended dosing, and alternative dosing and/or dose frequency with ISIS 721744 in patients with HAE
Secondary objectives 1
- 1. To evaluate the efficacy of extended dosing, and alternative dosing and/or dose frequency with ISIS 721744 in patients with HAE
Conditions and MedDRA coding
Hereditary Angioedema
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 23.1 | PT | 10019860 | Hereditary angioedema | 100000004850 |
Regulatory references
- 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 5
- 1. Satisfactory completion of ISIS 721744-CS2 (index study) through Week 17 with an acceptable safety and tolerability profile, per Sponsor and Investigator judgement
- 2. Able and willing to participate in a 64-week study
- 3. Females must be non-pregnant, non-lactating and either surgically sterile or post-menopausal
- 4. 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.
- 5. Participants must have access to, and the ability to use, ≥ 1 acute medication(s) (e.g., plasma-derived or recombinant C1- inhibitor (C1INH) concentrate or a bradykinin-2 [BK-2] antagonist) to treat angioedema attacks
Exclusion criteria 1
- 1. Have any new condition or worsening of an existing condition or change or anticipated change in medication or other reason, which in the opinion of the Investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating in or completing the study
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- 1. Percentage of Participants with at Least One Treatment-emergent Adverse Event (TEAE), Graded by Severity
Secondary endpoints 4
- 1. The time-normalized HAE attacks (monthly) by treatment
- 2. Plasma PKK levels, plasma proenzyme activation and cHK levels
- 3. Consumption of on-demand medications
- 4. Angioedema Quality of Life (AE-QoL) questionnaire score
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
PRD9568286 · Product
- Active substance
- Donidalorsen
- Pharmaceutical form
- INJECTION
- Route of administration
- SOLUTION FOR INJECTION
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Not Authorised
- MA holder
- IONIS PHARMACEUTICALS, INC.
- Paediatric formulation
- No
- Orphan designation
- No
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 7
| Organisation | City, country | Duties |
|---|---|---|
| Unisphere Travel Ltd. Inc. ORG-100043100
|
Norwood, United States | Other |
| Parexel International Corp. ORG-100007310
|
Durham, United States | Code 10 |
| MEDPACE LABORATORIES ORG-100042942
|
Leuven, Belgium | Laboratory analysis |
| PPD Development LP ORG-100011560
|
Richmond, United States | Other |
| Sitero LLC ORG-100047455
|
Coral Gables, United States | Data management, E-data capture |
| Inclin Inc. ORG-100044594
|
San Mateo, United States | Data management |
| Medpace Inc. ORG-100026760
|
Cincinnati, United States | On site monitoring, Code 12, Code 2 |
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Netherlands | Ended | 7 | 1 |
| Rest of world
United States
|
— | 13 | — |
Investigational sites
Amsterdam UMC Stichting
Interne Geneeskunde, Meibergdreef 9, 1105 AZ, Amsterdam
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Netherlands | 2020-10-22 | 2024-12-19 | 2020-11-02 | 2021-01-08 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Summary of results Art. 37(4) CTR
| Title | Submission date | Status | Type |
|---|---|---|---|
| 721744-CS3 Results- CTIS SUM-116280
|
2026-01-25T00:56:22 | Submitted | Summary of Results |
Layperson summary Annex V
| Title | Submission date | Status | Type |
|---|---|---|---|
| 721744-CS3 Plain Language Summary | 2026-01-25T01:00:31 | Submitted | Laypersons Summary of Results |
Documents 15 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Clinical study report (for publication) | m5352-isis-721744-cs3-s-app1611-protocol_Redacted | 1 |
| Clinical study report (for publication) | m5352-isis-721744-cs3-s-app1612-crf | 1 |
| Clinical study report (for publication) | m5352-isis-721744-cs3-s-app1619-sap_Redacted | 1 |
| Clinical study report (for publication) | m5352-isis-721744-cs3-s-csr-body_Redacted | 1 |
| Laypersons summary of results (for publication) | FINAL 721744-CS3 PLS_ Dutch | 1 |
| Laypersons summary of results (for publication) | FINAL 721744-CS3 PLS_English | 1 |
| Protocol (for publication) | D1_Protocol_ 2024-517249-15_Ionis_Redacted | AM3 |
| Protocol (for publication) | D1_Protocol_Clarification Letter_2024-517249-15_Ionis_Redacted | N/A |
| Protocol (for publication) | D1_Protocol_Sub-Study_2024-517249-15_Ionis_Redacted | Original |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_NL_Ionis_Blank | N/A |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main ICF_NL_Ionis_Redacted | 7.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Partner Pregnancy ICF_Ionis | 1.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Pregnancy ICF_Ionis | 1.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Sub-Study ICF Addendum_NL_Ionis_Redacted | 1.0 |
| Summary of results (for publication) | FINAL ISIS 721744-CS3_EU CTIS Results | 1 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-10-08 | Netherlands | Acceptable 2024-11-04
|
2024-11-04 |