What side effects are associated with this type of intervention?

Common treatments for Hereditary Angioedema (HAE) include C1 esterase inhibitors, bradykinin receptor antagonists, and kallikrein inhibitors. Side effects of these treatments can vary but often include injection site reactions, hypersensitivity reactions, and potential infections. For antisense oligonucleotides like Donidalorsen, side effects may include injection site reactions, flu-like symptoms, and liver enzyme elevations. It is important to monitor patients closely for any adverse effects during treatment.

What prior FDA approvals exist?

Hereditary Angioedema (HAE) has several FDA-approved treatments, primarily focusing on preventing and treating acute attacks. These include C1 esterase inhibitor (C1-INH) products like Berinert, Cinryze, and Haegarda, which replace the deficient or dysfunctional C1-INH protein. Other treatments include ecallantide (Kalbitor), a kallikrein inhibitor, and icatibant (Firazyr), a bradykinin B2 receptor antagonist. These treatments aim to manage the symptoms and frequency of HAE attacks. Donidalorsen, an antisense oligonucleotide targeting prekallikrein, represents a novel approach by reducing the production of prekallikrein, potentially offering a new mechanism for managing HAE.

What other types of research exist?

Promising novel alternatives to Donidalorsen for Hereditary Angioedema patients include Lanadelumab, a monoclonal antibody that inhibits plasma kallikrein, and Berotralstat, an oral plasma kallikrein inhibitor. Both have demonstrated efficacy in reducing HAE attack frequency and have been approved for prophylactic treatment of HAE.

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Antisense Oligonucleotide

Donidalorsen for Hereditary Angioedema

Phase 2

Waitlist Available

Research Sponsored by Ionis Pharmaceuticals, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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

Females must be non-pregnant, non-lactating and either surgically sterile or post-menopausal

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to week 221

Awards & highlights

No Placebo-Only Group

Summary

This trial uses donidalorsen, given as an injection under the skin, to help people with hereditary angioedema. The goal is to reduce the frequency and severity of their swelling episodes.

Who is the study for?

This trial is for individuals who have hereditary angioedema and completed a previous study (ISIS 721744-CS2) without safety concerns. Participants must be able to commit to a 64-week study, use effective contraception if of childbearing potential, and have access to acute medications for angioedema attacks.

What is being tested?

The trial is testing the extended use of donidalorsen administered subcutaneously in various dosing patterns or frequencies. It aims to assess the long-term safety and effectiveness of this treatment approach in people with hereditary angioedema.

What are the potential side effects?

While specific side effects are not listed here, participants from the initial study tolerated donidalorsen well. Potential side effects may include reactions at the injection site, allergic responses, or other issues as observed in earlier phases.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I can access and use medication for sudden swelling attacks.

Select...

I am not pregnant, not breastfeeding, and cannot have children due to surgery or menopause.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to week 221

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to week 221

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to week 221 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

Angioedema Quality of Life (AE-QoL) Questionnaire Score

Side effects data

From 2021 Phase 2 trial • 23 Patients • NCT04030598

33%

Application site rash

33%

Hyperhidrosis

33%

Vomiting

33%

Feeling hot

100%

80%

60%

40%

20%

Study treatment Arm

Part B: Donidalorsen 80 mg

Part A: Placebo

Part A: Donidalorsen 80 mg

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: DonidalorsenExperimental Treatment1 Intervention

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Donidalorsen

2021

Completed Phase 3

~150

0 / 2Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Hereditary Angioedema (HAE) treatments, such as Donidalorsen, work by targeting and reducing the production of specific proteins involved in the disease's pathogenesis. Donidalorsen is an antisense oligonucleotide that targets prekallikrein, a precursor to kallikrein, which is involved in the bradykinin pathway. By reducing prekallikrein levels, Donidalorsen decreases the production of bradykinin, a peptide that causes blood vessels to dilate and become more permeable, leading to the swelling characteristic of HAE attacks. This mechanism is crucial for HAE patients as it directly addresses the underlying cause of their symptoms, potentially reducing the frequency and severity of angioedema episodes.