Deucrictibant for Angioedema

(CHAPTER-3 Trial)

Recruiting in Palo Alto (17 mi)

+9 other locations

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Pharvaris Netherlands B.V.

Must not be taking: ACE inhibitors, Estrogens, CYP3A4 drugs

Disqualifiers: Non-HAE angioedema, Abnormal hepatic function, Renal impairment, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of once-daily orally administered deucrictibant extended-release tablet compared to placebo for prophylaxis to prevent angioedema attacks in participants aged ≥ 12 years with hereditary angioedema.

Will I have to stop taking my current medications?

You may need to stop taking certain medications before joining the trial. Specifically, you cannot use ACE inhibitors, estrogen-containing medications, or certain HAE treatments close to the screening period. Check with the trial team to see if your current medications are affected.

What data supports the effectiveness of the drug Deucrictibant for treating angioedema?

Research on a similar drug, Icatibant, shows it effectively reduces the time to resolve angioedema attacks, especially those related to certain blood pressure medications, from about 2 days to 10 hours. This suggests that drugs targeting bradykinin (a protein involved in inflammation) can be effective for angioedema.

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Eligibility Criteria

This trial is for adolescents and adults aged 12 years or older with hereditary angioedema (HAE), who have had at least three HAE attacks in the past three months. Participants must be able to manage acute HAE attacks, follow protocol requirements, and use contraception if applicable.

Inclusion Criteria

Provision of written informed consent/assent

Willing and able to adhere to all protocol requirements, including eDiary and ePRO data recording

I can get and use the needed medicine for sudden HAE attacks.

Exclusion Criteria

I am not pregnant, planning to become pregnant, or breast-feeding.

Known hypersensitivity to deucrictibant or any of the excipients of the study drug

I don't have any health issues that would make it unsafe for me to join the study.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive once-daily orally administered deucrictibant extended-release tablet or placebo for 24 weeks

24 weeks

Regular visits for efficacy and safety assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may roll over into the open-label study PHA022121-C307 (CHAPTER-4)

Participant Groups

The study tests a once-daily oral deucrictibant extended-release tablet against a placebo to prevent angioedema attacks. It's a Phase 3 trial where participants are randomly assigned to either the medication or placebo without knowing which one they receive.

Group I: Placebo Experimental Treatment 1 Intervention

Placebo 1 tablet by mouth once daily

Group II: Active Experimental Treatment 1 Intervention

Deucrictibant 40mg extended-release tablet by mouth once daily

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Study site Santa Monica, CA

Study site Walnut Creek, CA

Study Site Little Rock, AR

Study Site Saint Louis, MO

Who Is Running the Clinical Trial?

Pharvaris Netherlands B.V. Lead Sponsor

References

1. England pubmed.ncbi.nlm.nih.gov

Icatibant Compared to Steroids and Antihistamines for ACE-Inhibitor-Induced Angioedema. [2017] Article chosen Bas M, Greve J, Stelter K, et al. A Randomized Trial of Icatibant in ACE-Inhibitor-Induced Angioedema. N Engl J Med 2015;372:418-25. doi:10.1056/NEJMoa1312524.

2. United States pubmed.ncbi.nlm.nih.gov

C1-inhibitor therapy for hereditary angioedema attacks: prospective patient assessments of health-related quality of life. [2016] C1-inhibitor (INH) concentrate, which is recommended as first-line treatment for acute hereditary angioedema (HAE) attacks in many countries, was recently approved in the United States. We sought to solicit patients' feedback about their health-related quality of life (HRQoL) while being treated with C1-INH concentrate for acute HAE attacks under real-world conditions, as well as the personal impact of the availability of C1-INH on lifestyle and mental health domains. Subjects enrolled in an open-label study of C1-INH at 20 U/kg for acute HAE attacks were invited to participate in a prospectively designed survey to solicit "real-time" patient responses that were collected via an interactive voice response service or online with a personal computer. Eighteen subjects submitted 60 quarterly HRQoL and treatment impact survey responses over 29 months. Seventeen of 18 patients responding reported mean short form 12 HRQoL scores that were within a normal range. More than one-half indicated that C1-INH availability made them feel somewhat or much better, and >80% reported having a better outlook on the future and feeling more secure about the danger of life-threatening attacks. These data confirm a high level of HRQoL and a positive impact in lifestyle and emotional domains among patients who were treated for acute attacks of HAE with C1-INH concentrate.

3. England pubmed.ncbi.nlm.nih.gov

Management of patients with hereditary angioedema in Germany: comparison with other countries in the Icatibant Outcome Survey. [2020] The Icatibant Outcome Survey (IOS; NCT01034969) is a Shire-sponsored, international, observational study monitoring the safety and effectiveness of icatibant, a bradykinin B2 receptor antagonist approved for the acute treatment of adults with hereditary angioedema with C1 inhibitor deficiency (HAE-C1-INH).

4. Switzerland pubmed.ncbi.nlm.nih.gov

Icatibant for Multiple Hereditary Angioedema Attacks across the Controlled and Open-Label Extension Phases of FAST-3. [2015] In randomized, controlled, double-blind, multicenter phase 3 studies, one icatibant injection was efficacious and generally well tolerated in patients with a single hereditary angioedema (HAE) attack. Here, the efficacy and safety of icatibant for multiple HAE attacks was evaluated across the controlled and open-label extension phases of the For Angioedema Subcutaneous Treatment (FAST)-3 study (NCT00912093).

5. United States pubmed.ncbi.nlm.nih.gov

Icatibant: a novel approach to the treatment of angioedema related to the use of angiotensin-converting enzyme inhibitors. [2014] Angioedema related to the use of angiotensin-converting enzyme inhibitors (AE-ACEi) has, so far, been treated with antiallergic drugs with questionable results. Because angioedema in this setting is likely related to increased levels of bradikinin, we decided to use icatibant, a bradikinin receptor antagonist licensed for use in hereditary angioedema, in a patient with AE-ACEi. In the same patient, the time to resolution of the angioedema during previous attacks was about 2 days when classic antiallergic drug regimens were used; when icatibant was used, this time shortened to 10 hours. Icatibant is a promising drug in the treatment of AE-ACEi.