Oral deucrictibant to prevent and treat hereditary angioedema attacks
Oral Deucrictibant for the Prophylactic and Acute Treatment in Patients With Bradykinin Mediated Angioedema With Normal C1 Inhibitor (BK-AE-nC1INH)
This trial tests whether daily oral deucrictibant XR can prevent angioedema attacks and whether deucrictibant capsules can quickly relieve acute attacks in adults with bradykinin-mediated hereditary angioedema.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 10 (estimated) |
| Ages | 18 Years to 75 Years |
| Sex | All |
| Sponsor | Institute for Asthma and Allergy Research network |
| Drugs / interventions | omalizumab |
| Locations | 1 site (Wheaton, Maryland) |
| Trial ID | NCT07046806 on ClinicalTrials.gov |
What this trial studies
This two-part, randomized, double-blind, placebo-controlled crossover trial will enroll up to 10 adults with bradykinin-mediated angioedema to test both prophylactic and on-demand oral deucrictibant formulations. Part 1 compares deucrictibant XR tablets taken daily versus placebo for prevention of attacks, and Part 2 compares deucrictibant 20 mg soft capsules versus placebo for acute symptom relief. Participants will keep a symptom and dosing diary and must have access to FDA-approved on-demand angioedema medication for standard-of-care treatment. Safety and efficacy endpoints include attack frequency, time to symptom relief during attacks, patient-reported outcomes, and adverse events.
Who should consider this trial
Good fit: Adults (≥18) with clinically and laboratory-confirmed bradykinin-mediated angioedema, including HAE with normal C1INH, who have documented attacks and meet the diagnostic criteria are ideal candidates.
Not a fit: Patients with histamine-mediated angioedema, those who cannot use standard on-demand therapies, or those unable to attend the single study site are unlikely to benefit from participation.
Why it matters
Potential benefit: If successful, an effective oral medication could reduce attack frequency and offer a convenient at-home option for rapid relief of angioedema symptoms.
How similar studies have performed: Injectable bradykinin B2 receptor antagonists such as icatibant have demonstrated efficacy for acute HAE, but oral B2 antagonists like deucrictibant are a newer approach with limited prior clinical data.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:
1. Provision of written informed consent.
2. Male or female, aged ≥18 at the time of provision of informed consent.
3. Diagnosis of bradykinin-mediated angioedema based upon all of the following:
* Clinical history consistent with angioedema (subcutaneous or mucosal, nonpruritic swelling without accompanying urticaria), not responsive to treatments of anti-histamine, corticosteroid, and/or omalizumab.
* Tried and failed at least 2 weeks of cetirizine 20 mg twice a day (or its equivalent alternative antihistamines, such as fexofenadine, loratadine, desloratadine or levocetirizine, etc.).
* Total blood BK peptide levels following 3 days cold activation is above the diagnostic value in non-attack and/or attack period\*.
\*The "attack period" is defined as within 24 hours after an attack.
* Documented diagnostic testing results: C1INH antigen concentration and functional activity within normal range; C4 antigen concentration within normal range.
4. Documented history of at least 2 angioedema attacks in the previous 2 months.
5. Reliable access and experience to use standard of care medication to effectively manage acute angioedema attacks.
Exclusion Criteria:
1. Any diagnosis of angioedema other than BK-AE-nC1INH.
2. Participation in a clinical study with any other investigational drug within the previous 30 days or within 5 half-lives of the investigational drug at Screening (whichever was longer).
3. Exposure to angiotensin-converting enzyme (ACE) inhibitors or any estrogen-containing medications with systemic absorption (such as oral contraceptives or hormonal replacement therapy) within 4 weeks of Screening.
4. Receiving prophylactic treatment for BK-AE-nC1INH. Participants who have previously received prophylactic therapy but have stopped can participate in this study provided a sufficiently long washout period (≥5 half-life) is observed before the participant is screened. Exclusion includes use of:
• Short-term prophylaxis for BK-AE-nC1INH within 7 days prior to Screening.
5. Any females who are pregnant, plan to become pregnant, or are currently breast-feeding.
6. Abnormal hepatic function (aspartate aminotransferase \>2× upper limit of normal, alanine aminotransferase \>2× ULN, or total bilirubin \>1.5× upper limit of normal). Participants with Gilbert's syndrome, defined as isolated increase of total bilirubin ≤3× upper limit of normal and aspartate aminotransferase and alanine aminotransferase within the normal range, are not excluded.
7. Abnormal renal function (estimated glomerular filtration rate \[eGFR\] \<60 mL/min/1.73 m2).
8. Any clinically significant history of angina, myocardial infarction, syncope, stroke, left ventricular hypertrophy or cardiomyopathy, uncontrolled hypertension, bradycardia, or any other clinically significant cardiovascular abnormality within the previous year that, in the opinion of the Investigator, would interfere with the participant's safety or ability to participate in the study.
9. History of epilepsy and other significant neurological diseases.
10. Any clinically significant gastrointestinal dysfunction (eg, diarrhea, inflammatory bowel disease) which may impact on study drug absorption.
11. History of alcohol or drug abuse within the previous year, or current evidence of substance dependence or abuse.
12. Use of concomitant medications with systemic absorption that are moderate and strong inhibitors or strong inducers of CYP3A4, such as clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole, ritonavir, verapamil, and grapefruit juice as well as carbamazepine, and rifampin within the last 30◦days or within 5◦half-lives (whichever is longer) of the time of randomization.
13. Known hypersensitivity to deucrictibant or any of the excipients of study drug.
Where this trial is running
Wheaton, Maryland
- Institute For Asthma & Allergy — Wheaton, Maryland, United States (Recruiting)
Study contacts
- Study coordinator: Henry Li, MD
- Email: info@allergyasthma.us
- Phone: 301-962-5800
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.