Deucrictibant for Angioedema

(CHAPTER-4 Trial)

Recruiting at 8 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

Trial Summary

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.

What data supports the effectiveness of the drug Deucrictibant for treating angioedema?

Research on a similar drug, icatibant, shows it effectively reduces the time to resolve angioedema attacks, especially those related to certain blood pressure medications, from about 2 days to 10 hours. This suggests that drugs targeting similar pathways may be effective for angioedema. ^{1 2 3 4 5}

How is the drug Deucrictibant different from other treatments for angioedema?

Deucrictibant is unique because it may offer a novel approach to treating angioedema by targeting specific pathways involved in the condition, potentially providing faster relief compared to traditional treatments like steroids and antihistamines, which have shown questionable results in some cases. ^{1 3 5 6 7}

What is the purpose of this trial?

This is a Phase 3, multicenter, long-term, open-label study to evaluate the safety and efficacy of once-daily orally administered deucrictibant extended-release tablet for prophylaxis to prevent angioedema attacks in participants aged ≥12 years with Hereditary Angioedema

Research Team

Study Director, Pharvaris

Principal Investigator

Pharvaris Netherlands B.V.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: Deucrictibant Experimental Treatment 1 Intervention

Deucrictibant

Who Is Running the Clinical Trial?

Pharvaris Netherlands B.V.

Lead Sponsor

Trials

7

Recruited

610+

Findings from Research

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]

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]

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]

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]

References

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

Icatibant Compared to Steroids and Antihistamines for ACE-Inhibitor-Induced Angioedema. [2017]

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

C1-inhibitor therapy for hereditary angioedema attacks: prospective patient assessments of health-related quality of life. [2016]

3. England pubmed.ncbi.nlm.nih.gov

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

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

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

6. England pubmed.ncbi.nlm.nih.gov

Effect of icatibant on angiotensin-converting enzyme inhibitor-induced angioedema: A meta-analysis of randomized controlled trials. [2020]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Management of acute attacks of hereditary angioedema: potential role of icatibant. [2023]