Deucrictibant for Angioedema

(CHAPTER-4 Trial)

Recruiting at 26 trial locations

Overseen By Pharvaris Clinical Team

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Pharvaris Netherlands B.V.

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

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

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 130 weeks

130 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests deucrictibant, a once-daily tablet, to determine its safety and effectiveness in preventing hereditary angioedema (HAE) attacks, a condition causing sudden swelling. The goal is to see if this medication can help manage HAE without frequent attacks. Suitable candidates for this trial have been diagnosed with HAE and experienced at least one attack in the past three months. Participants must manage their HAE attacks with standard treatments and follow trial requirements, such as recording data in an electronic diary. As a Phase 3 trial, this study is the final step before FDA approval, offering participants the opportunity to contribute to the potential availability of a new treatment.

Do I need to stop my current medications to join the trial?

Yes, you may need to stop certain medications. Specifically, you cannot use ACE inhibitors, estrogen-containing medications, or certain prophylactic treatments for hereditary angioedema (HAE) close to the screening period. Check with the trial team for details on other medications.

Is there any evidence suggesting that deucrictibant is likely to be safe for humans?

Research has shown that deucrictibant is generally safe for patients. Studies have found it effective in preventing angioedema attacks in people with Hereditary Angioedema (HAE) over the long term. Earlier research indicated that most patients did not experience a return of symptoms after just one dose of deucrictibant. Safety checks, including physical exams, lab tests, and heart monitoring, confirmed its safety. Initial results suggest that deucrictibant can be a safe option for managing HAE, with no major side effects reported. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Deucrictibant is unique because it offers a new approach to treating angioedema by targeting the bradykinin B2 receptor. Unlike standard treatments such as C1 esterase inhibitors or icatibant, which manage symptoms after they appear, deucrictibant aims to prevent the swelling episodes associated with angioedema more proactively. This new mechanism of action could potentially provide faster and more effective relief for patients, reducing the frequency and severity of attacks. Researchers are excited because deucrictibant could offer a more efficient and targeted way to manage angioedema, improving quality of life for those affected by the condition.

What evidence suggests that deucrictibant might be an effective treatment for angioedema?

Research has shown that deucrictibant, the investigational treatment in this trial, can effectively reduce angioedema attacks. In previous studies, 93.1% of participants experienced at least a 50% reduction in attack frequency. Additionally, 55.2% of participants did not experience any attacks during the study. For individual attacks, 84.5% of participants saw their symptoms completely disappear within 24 hours, often after just one dose of deucrictibant. These results suggest that deucrictibant could be a promising option for managing hereditary angioedema. ^{2 6 7 8 9}

Who Is on the Research Team?

Study Director, Pharvaris

Principal Investigator

Pharvaris Netherlands B.V.

Are You a Good Fit for This Trial?

This trial is for adolescents and adults aged 12 years or older with Hereditary Angioedema (HAE), who have had at least one attack in the past three months. Participants must be able to manage acute HAE attacks, follow the study's procedures including eDiary entries, and females of childbearing age must agree to specified contraception methods.

Inclusion Criteria

I have signed the consent form.

I have had at least one attack in the last 3 months.

I am willing and able to follow all study rules and record my health data electronically.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive open-label deucrictibant extended-release tablet once daily for prophylaxis against angioedema attacks

130 weeks

Regular visits for safety and efficacy assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

End of Study visit

What Are the Treatments Tested in This Trial?

Interventions

• Deucrictibant

Trial Overview The trial is testing a once-daily oral tablet called Deucrictibant as a preventive treatment against angioedema attacks. It's an open-label Phase 3 study, meaning both researchers and participants know they're receiving the actual medication.

How Is the Trial Designed?

Group I: Deucrictibant Experimental Treatment 1 Intervention

Deucrictibant

Who Is Running the Clinical Trial?

Pharvaris Netherlands B.V.

Lead Sponsor

Trials

7

Recruited

610+

Published Research Related to This Trial

In a study involving 18 patients treated with C1-inhibitor concentrate for acute hereditary angioedema (HAE) attacks, most reported health-related quality of life (HRQoL) scores within a normal range, indicating effective management of their condition.

Over 50% of participants felt that the availability of C1-INH significantly improved their well-being, with more than 80% expressing a better outlook on their future and increased security regarding the risk of life-threatening attacks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

C1-inhibitor therapy for hereditary angioedema attacks: prospective patient assessments of health-related quality of life. Bewtra, AK., Levy, RJ., Jacobson, KW., et al.[2016]

Icatibant, a bradykinin receptor antagonist, significantly reduced the time to resolution of angioedema related to angiotensin-converting enzyme inhibitors (AE-ACEi) from about 2 days with traditional antiallergic drugs to just 10 hours.

This suggests that icatibant may be a more effective treatment option for AE-ACEi, particularly since angioedema in this context is likely linked to increased bradykinin levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Icatibant: a novel approach to the treatment of angioedema related to the use of angiotensin-converting enzyme inhibitors. Gallitelli, M., Alzetta, M.[2014]

Icatibant was found to be effective in providing symptom relief for multiple hereditary angioedema (HAE) attacks, with median times to relief ranging from 1.0 to 19.7 hours depending on the severity and location of the attack, based on a study involving 88 patients.

The treatment was generally well tolerated, although some adverse events were reported, including headache and recurrence of HAE attacks, with two serious events (arrhythmia and noncardiac chest pain) linked to icatibant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Icatibant for Multiple Hereditary Angioedema Attacks across the Controlled and Open-Label Extension Phases of FAST-3. Lumry, WR., Farkas, H., Moldovan, D., et al.[2015]

In a study of 685 patients with hereditary angioedema (HAE-C1-INH), German patients experienced significantly fewer severe attacks (38.7%) compared to patients from other countries (57.5%), indicating better management of the condition.

German patients also had better treatment outcomes with icatibant, showing shorter times to treatment (0.0 hours vs. 1.5 hours) and resolution (3.0 hours vs. 7.0 hours), suggesting that earlier intervention may lead to improved results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of patients with hereditary angioedema in Germany: comparison with other countries in the Icatibant Outcome Survey. Maurer, M., Bork, K., Martinez-Saguer, I., et al.[2020]

In a randomized trial involving patients with ACE-inhibitor-induced angioedema, icatibant was found to be effective in reducing symptoms, demonstrating its potential as a treatment option for this condition.

The study highlighted the safety profile of icatibant, showing that it was well-tolerated among participants, which is crucial for patients experiencing acute angioedema episodes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Icatibant Compared to Steroids and Antihistamines for ACE-Inhibitor-Induced Angioedema. Botnaru, T., Robert, A., Mottillo, S.[2017]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1081120625004594

Angioedema/Urticaria D005 LONG-TERM SAFETY AND ... Relative to study baseline, 93.1%/93.1%/79.3% of participants had ≥50%/≥70%/≥90% reduction in attack rate, respectively; 55.2% were attack free in the OLE.

2. ir.pharvaris.com ir.pharvaris.com/news-releases/news-release-details/pharvaris-announces-clinical-trial-data-highlighting

Pharvaris Announces Clinical Trial Data Highlighting ... Pharvaris Announces Clinical Trial Data Highlighting Deucrictibant for the Treatment of HAE to be Presented at the 2025 US HAEA National Summit.

3. ir.pharvaris.com ir.pharvaris.com/news-releases/news-release-details/pharvaris-presents-data-highlighting-potential-deucrictibant

Release Details - Investor Relations - Pharvaris N.V. 89.2% of the attacks that achieved symptom resolution at 24 hours were treated with a single dose of deucrictibant. Safety and Efficacy of Oral ...

4. jacionline.org jacionline.org/article/S0091-6749(25)00889-9/fulltext

Long-term prophylactic treatment with deucrictibant for ... This open-label study provides evidence that long-term prophylactic treatment with deucrictibant is effective, well tolerated, and safe in ...

5. annallergy.org annallergy.org/article/S1081-1206(24)00678-1/fulltext

RAPIDE-2 EXTENSION STUDY RESULTS In total, 84.5% of attacks achieved complete resolution within 24 hours, 90.2% of which with a single dose. Deucrictibant IR capsule was well-tolerated with no ...

6. ir.pharvaris.com ir.pharvaris.com/news-releases/news-release-details/data-supporting-potentially-differentiated-pharvaris-portfolio

Data Supporting the Potentially Differentiated Pharvaris ... Open-label prophylaxis data supporting the long-term safety profile and sustained benefits of deucrictibant, as well as clinical validation ...

7. jacionline.org jacionline.org/article/S0091-6749(24)00271-9/fulltext

Deucrictibant for angioedema due to acquired C1-inhibitor ... The safety data collected included physical examination findings, biochemistry analysis results, and electrocardiogram findings. The study ...

8. ir.pharvaris.com ir.pharvaris.com/news-releases/news-release-details/pharvaris-presents-data-supporting-ongoing-clinical-development

Pharvaris Presents Data Supporting Ongoing Clinical ... Deucrictibant data shows single-dose durability without symptom reoccurrence in the majority of HAE attacks treated; First-ever bradykinin ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT06679881

NCT06679881 | Long-Term, Open-label Study of Oral ... Long-Term, Open-label Study of Oral Deucrictibant Extended-Release Tablet for Prophylaxis Against Angioedema Attacks in Adolescents and Adults With HAE (CHAPTER ...