Oral Deucrictibant for Prophylactic and Acute Treatment in Hereditary Angioedema Patients

NCT07046806 | Recruiting Phase 1 FDA Drug

• 1 other identifier: IAA-PHA-ISR01a
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

To assess the efficacy of prophylactic treatment with deucrictibant extended release (XR) tablet versus placebo in preventing angioedema attacks, and to also assess the efficacy of deucrictibant soft capsules as on-demand treatment versus placebo in achieving angioedema symptom relief during acute attacks.

Conditions

Hereditary Angioedema (HAE); Angioedema; Bradykinin-mediated Angioedema; C1 Inhibitor Deficiency

Keywords

Bradykinin; deucrictibant; HAE; BK-AE-nC1INH; nC1INH; C1 Inhibitor; C4

Outcome Measures

Primary Outcomes (2)

• Part-1: Incidence and quality of HAE attacks comparing active versus placebo arms.

  Part-1: Time-normalized number of Investigator-confirmed moderate or severe angioedema attacks during the Treatment Period. Time-normalized number of Investigator-confirmed angioedema attacks treated with on-demand medication during the Treatment Period.

  24 weeks

• Part-2: Efficacy of active on-demand treatment versus placebo in achieving angioedema symptom relief during acute attacks

  Part-2: Time to onset of symptom relief of active drug versus placebo, defined as Patient Global Impression of Change (PGI-C) rating of at least "a little better" for 2 consecutive timepoints within 12 hours post-treatment. Time to complete symptom resolution, defined as achieving PGI-S rating of "none" within 48 hours post-treatment.

  16 weeks

Secondary Outcomes (2)

• Safety assessment of oral deucrictibant extended release (XR) tablet (Part 1), and deucrictibant oral on-demand tablets (Part 2).

  40 weeks

• Part-1: Change in Health-Related Quality of Life (HRQoL) Scores Between Active Drug and Placebo Periods

  16 weeks

Study Arms (4)

Deucrictibant XR tablet, 40 mg, prophylaxis

EXPERIMENTAL

Deucrictibant XR tablet, 40 mg, QD, oral use for 12 weeks

Drug: Deucrictibant XR tablet

Placebo to deucrictibant XR tablet, 40 mg, prophylaxis

PLACEBO COMPARATOR

Placebo tablets, 40 mg equivalent, QD, oral use for 12 weeks

Drug: Placebo comparator to XR tablet

On-demand deucrictibant 20 capsule, oral use

EXPERIMENTAL

Single 20 capsule orally for treatment of on-demand angioedema attack, for up to 16 weeks

Drug: Deucrictibant 20 mg capsule

Placebo comparator to on-demand deucrictibant 20 capsule, oral use

PLACEBO COMPARATOR

Placebo capsules for treatment of on-demand angioedema attacks, for up to 16 weeks

Drug: Placebo comparator to 20 mg capsule

Interventions

Deucrictibant XR tablet DRUG

Deucrictibant 40 mg XR tablet for prophylaxis

Also known as: Deucrictibant XR

Deucrictibant XR tablet, 40 mg, prophylaxis

Placebo comparator to XR tablet DRUG

Placebo comparator to deucrictibant 40 mg XR tablet, prophylaxis

Also known as: Placebo

Placebo to deucrictibant XR tablet, 40 mg, prophylaxis

Deucrictibant 20 mg capsule DRUG

Deucrictibant active drug for on-demand treatment of angioedma attacks

Also known as: Deucrictibant

On-demand deucrictibant 20 capsule, oral use

Placebo comparator to 20 mg capsule DRUG

Placebo comparator to Deucrictibant 20 mg capsule for on-demand treatment of angioedema attacks

Also known as: Placebo

Placebo comparator to on-demand deucrictibant 20 capsule, oral use

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of written informed consent.
• Male or female, aged ≥18 at the time of provision of informed consent.
• 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.
• Documented history of at least 2 angioedema attacks in the previous 2 months.
• Reliable access and experience to use standard of care medication to effectively manage acute angioedema attacks.

You may not qualify if:

• Any diagnosis of angioedema other than BK-AE-nC1INH.
• 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).
• 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.
• Short-term prophylaxis for BK-AE-nC1INH within 7 days prior to Screening.
• Any females who are pregnant, plan to become pregnant, or are currently breast-feeding.
• 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.
• Abnormal renal function (estimated glomerular filtration rate \[eGFR\] \<60 mL/min/1.73 m2).
• 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.
• History of epilepsy and other significant neurological diseases.
• Any clinically significant gastrointestinal dysfunction (eg, diarrhea, inflammatory bowel disease) which may impact on study drug absorption.
• History of alcohol or drug abuse within the previous year, or current evidence of substance dependence or abuse.
• 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.
• Known hypersensitivity to deucrictibant or any of the excipients of study drug.

Sponsors & Collaborators

• Institute for Asthma and Allergy: lead

Study Sites (1)

Institute For Asthma & Allergy

Wheaton, Maryland, 20902, United States

RECRUITING

Related Publications (3)

• Weller K, Groffik A, Magerl M, Tohme N, Martus P, Krause K, Metz M, Staubach P, Maurer M. Development and construct validation of the angioedema quality of life questionnaire. Allergy. 2012 Oct;67(10):1289-98. doi: 10.1111/all.12007. Epub 2012 Aug 23.

  PMID: 22913638 BACKGROUND

• Riedl MA, Danese M, Danese S, Ulloa J, Maetzel A, Audhya PK. Hereditary Angioedema With Normal C1 Inhibitor: US Survey of Prevalence and Provider Practice Patterns. J Allergy Clin Immunol Pract. 2023 Aug;11(8):2450-2456.e6. doi: 10.1016/j.jaip.2023.01.023. Epub 2023 Jan 30.

  PMID: 36720386 BACKGROUND

• Lumry WR, Li HH, Levy RJ, Potter PC, Farkas H, Moldovan D, Riedl M, Li H, Craig T, Bloom BJ, Reshef A. Randomized placebo-controlled trial of the bradykinin B(2) receptor antagonist icatibant for the treatment of acute attacks of hereditary angioedema: the FAST-3 trial. Ann Allergy Asthma Immunol. 2011 Dec;107(6):529-37. doi: 10.1016/j.anai.2011.08.015. Epub 2011 Oct 5.

  PMID: 22123383 BACKGROUND

MeSH Terms

Conditions

Angioedemas, Hereditary; Angioedema

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Immunologic Deficiency Syndromes

Central Study Contacts

Henry Li, MD

CONTACT

301-962-5800; info@allergyasthma.us

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2025
• First Posted: July 2, 2025
• Study Start: March 10, 2025
• Primary Completion: April 1, 2026
• Study Completion: April 1, 2026
• Last Updated: July 2, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: After 9 months post publication date of the clinical trial data.
• Access Criteria: Any qualified researchers engaging in independent scientific research.

Locations

US (1)