Phase 2
Completed N=23
A Study to Assess the Clinical Efficacy of Donidalorsen (Also Known as IONIS-PKK-LRx and ISIS 721744) in Participants With Hereditary Angioedema
Source: ClinicalTrials.gov NCT04030598 ↗Enrolled (actual)
23
Serious AEs
0.0%
Results posted
Sep 2022
Primary outcomePrimary: Time-normalized Number of HAE Attacks (Per Month) From Week 1 to Week 17 — 2.21; 0.23; 1.52 HAE attacks per month — p=0.001
Summary
The purpose of this study was to evaluate the clinical efficacy, safety, and tolerability of donidalorsen in participants with hereditary angioedema (HAE) type 1 (HAE-1), HAE type 2 (HAE-2), or HAE with normal C1-inhibitor (C1-INH) and to evaluate the effect of donidalorsen on plasma prekallikrein (PKK) and other relevant biomarkers.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Time-normalized Number of HAE Attacks (Per Month) From Week 1 to Week 17 |
2.21; 0.23; 1.52 | 0.001 sig |
| SECONDARY Time-normalized Number of Investigator-confirmed HAE Attacks (Per Month) From Week 5 to Week 17 |
2.06; 0.07; 1.78 | 0.003 sig |
| SECONDARY Time-normalized Number of Moderate or Severe Investigator-confirmed HAE Attacks (Per Month) From Week 5 to Week 17 |
1.25; 0.05; 0.89 | 0.004 sig |
| SECONDARY Number of Participants With Clinical Response by Week 17 |
2; 13; 2; 1; 12; 2 | 0.004 sig |
| SECONDARY Number of Investigator-confirmed HAE Attacks Requiring Acute Therapy From Week 5 to Week 17 |
1.25; 0.05; 0.89 | 0.009 sig |
| SECONDARY Percentage of Cleaved High Molecular Weight Kininogen (cHMWK) Levels at Weeks 9 and 17 |
5.62; 2.07; 1.03; 7.00; 2.35; 2.13 | — |
| SECONDARY Prekallikrein (PKK) Activity Levels at Weeks 9 and 17 |
95.467; 37.676; 25.630; 98.600; 37.795; 28.615 | — |
| SECONDARY Number of Participants Who Consumed On-demand Medication at Weeks 9 and 17 |
6; 12; 3; 6; 11; 3 | 1.000 |
| SECONDARY Change From Baseline in Angioedema Quality of Life (AE-QoL) Questionnaire Total Score at Weeks 9 and 17 |
-1.50; -27.42; 25.49; -6.15; -26.85; 26.96 | — |
Eligibility Criteria
Inclusion Criteria
- Documented diagnosis of HAE-1/HAE-2 (for inclusion in Part A) or HAE-nC1-INH (for inclusion in Part B)
- Participants must have experienced a minimum of 2 HAE attacks (assessed by the Angioedema Activity Score [AAS] and confirmed by the investigator) during the screening period
- Access to, and the ability to use, ≥ 1 acute medication(s) to treat angioedema attacks
Exclusion Criteria
- Anticipated use of short-term prophylaxis for angioedema attacks for a pre-planned procedure during the screening or study periods
- Concurrent diagnosis of any other type of recurrent angioedema, including acquired or idiopathic angioedema
- Known history of or positive test for human immunodeficiency virus (HIV), hepatitis C, or chronic hepatitis B
- Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated
- Treatment with another investigational drug or biological agent within 1 month or 5 half-lives, whichever is longer, of screening
- Exposure to any of the following medications:
- Angiotensin-converting enzyme (ACE) inhibitors or any estrogen-containing medications with systemic absorption (such as oral contraceptive or hormonal replacement therapy) within 4 weeks prior to screening
- Chronic prophylaxis with Lanadelumab within 10 weeks prior to screening
- Oligonucleotides (including small interfering ribonucleic acid [RNA]) within 4 months of screening (if single dose received) or within 12 months of screening (if multiple doses received)
Data sourced from ClinicalTrials.gov (NCT04030598). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.