Deucrictibant for Hereditary Angioedema

(RAPIDe-2 Trial)

Enrolling by invitation at 68 trial locations

Overseen By Pharvaris Clinical Team

Age: Any Age

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Pharvaris Netherlands B.V.

Must not be taking: Lanadelumab, C1-esterase inhibitors

Disqualifiers: Pregnancy, Systemic diseases, Substance abuse, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 54 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new oral treatment called deucrictibant (PHA-022121) to determine its safety and effectiveness for treating sudden hereditary angioedema (HAE) attacks, including those affecting the throat. The goal is to offer a reliable option for individuals experiencing these severe episodes. It welcomes participants who have previously joined studies with this treatment and experienced at least one HAE attack treated in those studies. As a Phase 2, Phase 3 trial, this research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, giving participants a chance to contribute to potentially groundbreaking advancements in HAE treatment.

Will I have to stop taking my current medications?

The trial requires that you stop using certain medications like lanadelumab, C1-esterase inhibitors, oral kallikrein inhibitors, attenuated androgens, anti-fibrinolytics, or monoclonal HAE therapy before enrolling. If you are on long-term HAE medications like plasma-derived C1-INH, danazol, anti-fibrinolytics, berotralstat, or lanadelumab, you must be on a stable dose for at least 3 months before joining and plan to stay on that dose during the study.

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

Research shows that deucrictibant, a treatment for hereditary angioedema (HAE), holds promise in managing this condition. Studies have found that deucrictibant can effectively treat and even prevent sudden swelling episodes, known as angioedema attacks, including those in the throat area, which can be particularly dangerous.

Previous data suggest that a single dose of deucrictibant can stop symptoms for most attacks without recurrence, indicating its safety and effectiveness. Additionally, the treatment may be useful for other types of angioedema, suggesting it is generally safe.

While specific side effects are not detailed, ongoing research and trials aim to ensure the treatment's safety for long-term use. As this trial is in advanced stages, a substantial amount of safety data is available. So far, deucrictibant has been well-tolerated in earlier studies. It is important to consult healthcare providers to understand potential risks and benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for hereditary angioedema?

Unlike the standard treatments for hereditary angioedema, which include C1 inhibitors, bradykinin receptor antagonists, and kallikrein inhibitors, deucrictibant offers a novel approach by being a selective bradykinin B2 receptor antagonist. Researchers are excited about deucrictibant because it directly targets the pathway responsible for the painful and potentially dangerous swelling episodes characteristic of the disease. This new mechanism of action could provide rapid relief from symptoms and potentially reduce the frequency of attacks, offering a promising alternative to current therapies.

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

Research has shown that deucrictibant effectively treats hereditary angioedema (HAE) attacks. In one study, 89.2% of HAE attacks experienced symptom relief within 24 hours after a single dose of deucrictibant. The treatment also provided long-lasting effects, with symptoms not returning quickly. Additionally, long-term studies have found deucrictibant to be safe and effective for managing attacks over time. This treatment targets bradykinin, a substance in the body that can cause swelling, and helps reduce these reactions. Overall, the evidence supports its potential in effectively managing HAE attacks. ^{1 2 5 6 7}

Who Is on the Research Team?

Study Director

Principal Investigator

Pharvaris Netherlands B.V.

Are You a Good Fit for This Trial?

This trial is for patients with Hereditary Angioedema (HAE) due to C1-INH deficiency who have taken at least one dose of the study drug in a previous related trial. Participants must not be pregnant, breastfeeding, or have any condition that could affect their safety or participation. They also shouldn't be on certain other HAE treatments or drugs affecting liver enzymes.

Inclusion Criteria

Must have received at least 1 dose of study drug (including the non-attack visit) in Study PHA022121-C201.

I have been diagnosed with Hereditary Angioedema type I or II.

Signed and dated informed consent form

Exclusion Criteria

I do not have any health conditions that would make it unsafe for me to join the study.

You have a heart problem that shows up on a special heart test.

Pregnancy or breast-feeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive on-demand treatment with orally administered deucrictibant for acute hereditary angioedema attacks

54 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• PHA-022121

Trial Overview The study tests long-term use of deucrictibant at various doses for treating sudden HAE attacks. It's an extension from a prior study and focuses on oral administration effectiveness and safety over time, including its impact on severe throat swelling attacks.

How Is the Trial Designed?

Group I: Part B: Selected dose Experimental Treatment 1 Intervention

Single dose of deucrictibant

Who Is Running the Clinical Trial?

Pharvaris Netherlands B.V.

Lead Sponsor

Trials

7

Recruited

610+

Published Research Related to This Trial

Icatibant is a safe and effective treatment for acute attacks of hereditary angioedema in adults, with clinical evidence supporting its use and only 10% of patients needing a second dose.

The most common side effects are mild and localized, such as pain and swelling at the injection site, and no serious adverse reactions have been reported, making it a favorable option for self-administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evidence-based review of the potential role of icatibant in the treatment of acute attacks in hereditary angioedema type I and II. Floccard, B., Hautin, E., Bouillet, L., et al.[2021]

Patients with hereditary angioedema with normal C1 inhibitor (HAE-nC1 INH) tend to be older at disease onset and experience more abdominal and laryngeal attacks compared to those with HAE type I.

Icatibant is effective for treating angioedema attacks in both HAE-nC1 INH and HAE type I, but it takes longer to resolve attacks in HAE-nC1 INH patients, with no serious side effects reported, highlighting its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hereditary angioedema with normal C1 inhibitor in a French cohort: Clinical characteristics and response to treatment with icatibant. Bouillet, L., Boccon-Gibod, I., Launay, D., et al.[2018]

Allowing patients to self-administer icatibant for acute hereditary angioedema (HAE) can save an average of €121.30 per attack compared to administration by health professionals, leading to significant annual savings for the Spanish National Health System.

The economic evaluation suggests that self-administration not only reduces direct healthcare costs but also lowers indirect costs related to productivity losses, potentially saving Spain between €90,319 and €2,315,360 annually.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Social costs of icatibant self-administration vs. health professional-administration in the treatment of hereditary angioedema in Spain. Blasco, AJ., Lázaro, P., Caballero, T., et al.[2021]

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. 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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40882771/

Long-term prophylactic treatment with deucrictibant for ... Conclusion: Deucrictibant extended-release tablet effectively prevented angioedema attacks in patients with AAE-C1INH, without safety concerns.

4. 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 ...

5. jacionline.org jacionline.org/article/S0091-6749(24)01949-3/fulltext

Long-Term Safety and Efficacy of Oral Deucrictibant for ... Results of the RAPIDe-2 extension study provide evidence on the long-term safety and efficacy of deucrictibant IR capsule for treatment of HAE attacks.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05396105

NCT05396105 | Extension Study of Oral PHA-022121 for ... This study evaluates the safety and efficacy of long-term on-demand treatment with orally administered deucrictibant for acute hereditary angioedema (HAE) ...

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

Deucrictibant for angioedema due to acquired C1-inhibitor ... Deucrictibant has the potential to effectively and safely treat and prevent angioedema attacks due to acquired C1-inhibitor deficiency.