Deucrictibant for Angioedema

(CHAPTER-3 Trial)

Recruiting at 65 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 drugs

Disqualifiers: Non-HAE angioedema, Abnormal hepatic function, 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: 24 weeks

81 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called deucrictibant to determine if it can prevent attacks of hereditary angioedema (HAE), a condition causing sudden and severe swelling. The study compares the effects of deucrictibant, taken as a daily pill, to a placebo (a pill with no active drug). Researchers aim to discover if deucrictibant can safely and effectively reduce the frequency of these swelling attacks. Individuals who have experienced at least three HAE attacks in the past three months and can manage their attacks with current treatments might be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the development of a potentially groundbreaking treatment.

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.

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

Research has shown that deucrictibant appears safe for preventing angioedema, which is swelling under the skin. In one study where patients knew they were taking deucrictibant, long-term use supported its safety and effectiveness. The study found deucrictibant could be used safely, with no major problems reported.

Another study examined potential issues through physical exams, lab tests, and heart monitoring while using deucrictibant. The results did not reveal any significant side effects, suggesting the treatment is generally well-tolerated.

Overall, these studies provide strong evidence that deucrictibant is safe for people with hereditary angioedema. While no treatment is without risk, the data so far is encouraging for those considering joining this trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about deucrictibant for angioedema because it introduces a new mechanism of action. Most treatments for angioedema, like antihistamines and corticosteroids, aim to reduce inflammation or suppress the immune response. However, deucrictibant works differently by targeting the bradykinin B2 receptor, which is directly involved in the swelling and pain associated with angioedema. This targeted approach might offer quicker relief and improved outcomes for patients, setting it apart from current therapies. Additionally, its once-daily, extended-release tablet form makes it convenient for patients to use.

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

Studies have shown that deucrictibant effectively prevents swelling attacks in people with hereditary angioedema. In some research, 89.2% of the attacks resolved within 24 hours with just one dose of the treatment. Additionally, long-term use of deucrictibant significantly reduced the number of attacks, with over 79% of participants experiencing at least a 90% decrease in attack frequency. Another study found that more than half of the participants were completely free of attacks over time. These findings suggest that deucrictibant could be a promising option for managing hereditary angioedema. Participants in this trial will receive either deucrictibant or a placebo to further evaluate its effectiveness. ^{3 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 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

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

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

History of alcohol or drug abuse within the previous year, or current evidence of substance dependence or abuse

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

• Deucrictibant

Trial Overview 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.

How Is the Trial Designed?

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

Who Is Running the Clinical Trial?

Pharvaris Netherlands B.V.

Lead Sponsor

Trials

7

Recruited

610+

Published Research Related to This Trial

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 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]

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]

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]

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]

Citations

1. 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 ...

2. 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 ...

3. 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.

4. 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.

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. 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 ...

8. 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 ...

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 ...