Deucrictibant for Hereditary Angioedema

(RAPIDe-3 Trial)

No longer recruiting at 85 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: Attenuated androgens, CYP3A4 inhibitors

Disqualifiers: Pregnancy, Angioedema, Hepatic, Renal, 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: 2

Duration: Varies per attack

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of an oral medication called deucrictibant for treating sudden attacks in people with hereditary angioedema (HAE), a condition that causes painful swelling. Participants will receive either deucrictibant or a placebo for their first attack, then switch for their second attack, allowing researchers to compare the results. The trial seeks individuals who have experienced at least two HAE attacks in the last three months and have managed these attacks with standard treatments. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new treatment.

Do I have to stop taking my current medications for the trial?

If you are on long-term prophylactic medication for HAE, you must either stay on a stable dose or have stopped using certain medications like plasma-derived C1-INH at least 2 weeks or lanadelumab at least 10 weeks before screening. Other medications, especially those affecting CYP3A4, may need to be stopped 30 days before the trial.

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

Research has shown that deucrictibant is generally well tolerated. In one study, only three treatment-related side effects occurred, all in a single participant. This suggests that most people did not experience serious side effects. Researchers are testing deucrictibant for hereditary angioedema (HAE), a rare condition causing sudden swelling. Studies have examined both prevention and treatment of these swelling attacks. The results are promising, indicating that deucrictibant is relatively safe. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Deucrictibant is unique because it offers a fresh approach to treating hereditary angioedema (HAE). Unlike current treatments like C1 inhibitors or bradykinin receptor antagonists, deucrictibant works by targeting different aspects of the inflammatory process responsible for HAE attacks. Researchers are excited about deucrictibant because it might provide faster relief during an attack and potentially improve the quality of life for patients by offering an effective alternative when other treatments may not work as well. Its novel mechanism of action could make it a game-changer for those dealing with the unpredictable and often debilitating symptoms of HAE.

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

Studies have shown that deucrictibant effectively reduces attacks of hereditary angioedema (HAE). One study demonstrated that deucrictibant lowered the average number of monthly attacks by 84.5%, a significant reduction. Other research found that symptoms improved noticeably within the first few hours after treatment. This trial will evaluate deucrictibant's effectiveness by administering it for the first HAE attack in one arm and for the second HAE attack in another arm, using a placebo for the alternate attack. This evidence suggests that deucrictibant can quickly and effectively manage HAE attacks, supporting its potential in managing HAE. ^{1 2 5 6 7}

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 to 75 with Hereditary Angioedema (HAE) types 1 or 2. It's suitable for those who experience HAE attacks, including non-severe throat swelling, and some may be on long-term prevention meds.

Inclusion Criteria

Provision of written informed consent/assent

I am between 12 and 75 years old.

Capable of recording, without assistance, electronic HAE diary and ePRO data using an electronic device

Exclusion Criteria

I have previously been treated with deucrictibant for HAE.

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

Any female who is pregnant, plans to become pregnant, or is breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized and receive double-blinded study drug to treat 2 qualifying HAE attacks

Varies per attack

2 visits (in-person) for each attack treatment

Follow-up

Participants are monitored for safety and effectiveness after the second attack treated with study drug

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Deucrictibant

Trial Overview The study tests Deucrictibant soft capsules against a placebo when an HAE attack occurs. It's a Phase 3 trial where participants are randomly assigned to receive either the real drug or placebo in different periods without knowing which one they're taking.

How Is the Trial Designed?

Group I: Arm 2 Experimental Treatment 1 Intervention

Placebo administered for first HAE attack, deucrictibant administered for second HAE attack.

Group II: Arm 1 Experimental Treatment 1 Intervention

Deucrictibant administered for first HAE attack, placebo administered for second HAE attack.

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]

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]

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]

Hereditary angioedema is caused by a deficiency or dysfunction of C1-inhibitor, leading to excessive bradykinin release, which can result in life-threatening swelling, especially in the upper respiratory tract.

Icatibant, a selective bradykinin B2-receptor antagonist, shows promise as a new treatment option for angioedema, particularly for patients who cannot tolerate ACE-inhibitors, expanding the therapeutic options beyond the traditional C1-inhibitor extract.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Allergy-immunology. New therapies for acute attacks in hereditary angioedema]. Leimgruber, A.[2013]

In a clinical trial involving 77 patients with hereditary angioedema, BCX7353 significantly reduced the rate of angioedema attacks by 73.8% at a daily dose of 125 mg or more compared to placebo.

The treatment also improved quality of life for patients at the 125 mg and 250 mg doses, although mild gastrointestinal side effects were the most common adverse events reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Plasma Kallikrein Inhibitor for Prophylaxis in Hereditary Angioedema. Aygören-Pürsün, E., Bygum, A., Grivcheva-Panovska, V., et al.[2018]

Citations

1. ir.pharvaris.com ir.pharvaris.com/news-releases/news-release-details/pharvaris-announces-positive-top-line-phase-2-data-chapter-1

Pharvaris Announces Positive Top-line Phase 2 Data from the ... Primary endpoint met; 40 mg/day orally administered deucrictibant significantly reduced mean monthly attack rate by 84.5% (p=0.0008) ...

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-present-phvs416-and-phvs719-clinical-data-treatment

Pharvaris to Present PHVS416 and PHVS719 Clinical Data for ... PHVS719 is designed to be a once-daily prophylactic treatment for the prevention of HAE attacks, as supported by data demonstrating compound absorption in the ...

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

Long-term prophylactic treatment with deucrictibant for ... The primary end point was the time-normalized number of investigator-confirmed angioedema attacks per 28 days of exposure to deucrictibant ...

5. firstwordpharma.com firstwordpharma.com/story/5750346

Data of Deucrictibant for the On-Demand Treatment of HAE ... Posters highlight clinically meaningful improvement in HAE symptoms observed in the first hours after treatment with PHVS416 (deucrictibant ...

6. ir.pharvaris.com ir.pharvaris.com/news-releases/news-release-details/deucrictibant-data-highlighted-multiple-presentations-c1

Deucrictibant Data Highlighted in Multiple Presentations at the ... In the attack-treatment phase, PHVS416 was generally well tolerated with three treatment-related adverse events (TRAEs) reported for one PHVS416 ...

7. haea.org haea.org/page/show/press/342/Pharvaris_Announces_FDA_Lifting_of_the_Clinical_Hold_of_Deucrictibant_for_the_Prophylactic_Treatment_of_HAE_Attacks

US Hereditary Angioedema Association Phase 2 CHAPTER-1 study of deucrictibant for the prophylactic treatment of HAE attacks. About Deucrictibant Deucrictibant is a potent, selective ...