Deucrictibant for Hereditary Angioedema

(RAPIDe-3 Trial)

Recruiting at 73 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

120 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled, 2-period, 2-treatment cross-over study to evaluate the efficacy and safety of orally administered deucrictibant compared to placebo for the on-demand treatment of HAE attacks, including non-severe laryngeal attacks, in participants ≥12 to ≤75 years of age with HAE type 1, type 2, or type 3, a proportion of whom are using long-term prophylactic medication for HAE.

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.

What makes the drug Deucrictibant unique for treating hereditary angioedema?

Deucrictibant is unique because it is an oral treatment option for hereditary angioedema, unlike icatibant, which is administered subcutaneously (under the skin). This oral administration could offer more convenience and ease of use for patients. ^{1 2 3 4 5}

Research Team

Study Director, Pharvaris

Principal Investigator

Pharvaris Netherlands B.V.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

References

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

Management of patients with hereditary angioedema in Germany: comparison with other countries in the Icatibant Outcome Survey. [2020]

2. Germany pubmed.ncbi.nlm.nih.gov

Social costs of icatibant self-administration vs. health professional-administration in the treatment of hereditary angioedema in Spain. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

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

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]

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

Oral Plasma Kallikrein Inhibitor for Prophylaxis in Hereditary Angioedema. [2018]