Oral PHA-022121 for Hereditary Angioedema

(HAE CHAPTER-1 Trial)

No longer recruiting at 39 trial locations
PC
Overseen ByPharvaris Clinical Team
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new oral medication, PHA-022121, to determine its safety and effectiveness in preventing attacks in people with hereditary angioedema (HAE), a condition that causes sudden swelling. In the first part, participants receive either a low dose, a high dose, or a placebo (a pill with no active medicine) to compare results. In the second part, all participants receive the high dose. The trial seeks individuals diagnosed with HAE type I or II who have experienced at least three swelling attacks in the last three months or two during the screening period. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop using certain medications like C1-esterase inhibitors, oral kallikrein inhibitors, attenuated androgens, anti-fibrinolytics, or monoclonal HAE therapy before enrolling. The protocol does not specify the exact time period for stopping these medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that deucrictibant, the main ingredient in PHA-022121, has been tested for safety in people with hereditary angioedema (HAE). In earlier studies, patients generally tolerated deucrictibant well. Safety checks, including physical exams, blood tests, and heart monitoring, found no major safety issues. Another study confirmed its long-term safety for preventing HAE attacks.

Moreover, deucrictibant has shown good results in both preventing and treating HAE attacks as needed. This indicates that the treatment is safe for people with HAE in different situations. While side effects can occur, these studies have reported no serious side effects.12345

Why are researchers excited about this trial's treatments?

Unlike current treatments for hereditary angioedema, which often involve injections or infusions, PHA-022121 offers an oral option, making it more convenient for patients. This investigational drug, deucrictibant, works by inhibiting the bradykinin B2 receptor, a novel approach compared to traditional C1 esterase inhibitors and kallikrein inhibitors. Researchers are excited about the potential for PHA-022121 to provide rapid relief of symptoms through a less invasive delivery method, potentially enhancing patient comfort and adherence.

What evidence suggests that this trial's treatments could be effective for hereditary angioedema?

Research has shown that PHA-022121, also known as deucrictibant, may help treat hereditary angioedema (HAE). In one study, 86.9% of patients experienced complete resolution of swelling attacks within 24 hours. Another study suggested the drug could benefit those with a type of swelling related to HAE. Long-term research has also indicated that deucrictibant is safe and effective for managing HAE attacks. In this trial, participants will receive either a low or high dose of deucrictibant, or a placebo, to evaluate its effectiveness in preventing attacks in people with hereditary angioedema.13678

Who Is on the Research Team?

MR

Marc Riedl, MD

Principal Investigator

UC San Diego, La Jolla, California, United States

EA

Emel Aygören-Pürsün, MD

Principal Investigator

University Hospital Frankfurt - Goethe University, Frankfurt, Germany

Are You a Good Fit for This Trial?

This trial is for people with Hereditary Angioedema (HAE) types I or II who've had at least 3 attacks in the last 3 months, or a minimum of 2 during screening. They must be able to use standard acute attack meds and sign consent forms. It's not for pregnant/breastfeeding individuals, those with significant health issues that could affect safety/participation, recent drug abuse history, abnormal kidney/liver function, or if they've used certain HAE treatments/drugs recently.

Inclusion Criteria

I can access and know how to use emergency medications.
I have been diagnosed with Hereditary Angioedema type I or II.
Signed and dated informed consent form
See 1 more

Exclusion Criteria

I do not have any health conditions that would make it unsafe for me to join the study.
Participation in any other investigational drug study within defined period
I haven't taken specific medications for swelling attacks before joining this study.
See 5 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

up to 8 weeks

Treatment Part 1

Participants are randomized to receive either a low dose, high dose of PHA-022121, or placebo for 12 weeks

12 weeks

Treatment Part 2

Participants continue in a single open-label arm receiving a high dose of PHA-022121 for 30 months

30 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • PHA-022121
  • Placebo
Trial Overview The study tests PHA-022121 taken orally to prevent angioedema attacks in HAE patients. It has two parts: Part 1 randomly assigns patients to low/high doses of the drug or placebo for 12 weeks; all move to Part 2 afterwards for an open-label extension lasting up to 30 months.
How Is the Trial Designed?
4Treatment groups
Experimental Treatment
Placebo Group
Group I: Part 2: Open-labelExperimental Treatment1 Intervention
Group II: Part 1: Low doseExperimental Treatment1 Intervention
Group III: Part 1: High doseExperimental Treatment1 Intervention
Group IV: Part 1: PlaceboPlacebo Group1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

Pharvaris Netherlands B.V.

Lead Sponsor

Trials
7
Recruited
610+

Published Research Related to This Trial

Emerging therapies for hereditary angioedema (HAE), including C1 esterase replacement, kallikrein inhibitors, and bradykinin receptor 2 antagonists, have shown promise in phase 1 and phase 2 trials, indicating their potential effectiveness in treating HAE.
The clinical trials are well-designed, being double-blind and placebo-controlled, and they focus on patients with confirmed low C1 inhibitor levels, suggesting a robust approach to developing new treatments for HAE.
Hereditary angiodema: a current state-of-the-art review, VI: novel therapies for hereditary angioedema.Frank, MM.[2019]
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.
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]
Orladeyo (berotralstat) is an effective once-daily oral medication for preventing hereditary angioedema (HAE) attacks, showing a 67% reduction in attacks in the ongoing phase III APeX-2 trial.
The drug has demonstrated a favorable safety profile with mostly mild to moderate gastrointestinal side effects and minimal serious adverse effects, making it a convenient alternative to traditional subcutaneous or intravenous therapies.
A review of oral kallikrein inhibitor berotralstat for hereditary angioedema.Gao, Y., Hwang, J., Hwang, G., et al.[2022]

Citations

Pharvaris Presents Data Supporting Ongoing Clinical ...The median time to complete attack resolution was 10.6 hours, and 86.9% of attack achieved complete resolution at 24 hours. Eighty-nine percent ...
Release Details - Investor Relations - Pharvaris N.V.We shared data demonstrating the potential for deucrictibant to address the unmet needs of people living with bradykinin-mediated angioedema beyond HAE-1/2.
NCT04618211 | Dose-ranging Study of Oral PHA-022121 ...This study evaluates the efficacy of orally administered deucrictibant for the acute treatment of attacks in patients with hereditary angioedema (HAE).
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.
Pharvaris Announces Clinical Trial Data Highlighting ...Pharvaris is currently evaluating the efficacy and safety of deucrictibant in a pivotal Phase 3 study for the prevention of HAE attacks.
Pharvaris Announces Clinical Trial Data Highlighting ...With positive data in both Phase 2 prophylaxis and on-demand studies in HAE, Pharvaris is currently evaluating the efficacy and safety of ...
Deucrictibant for angioedema due to acquired C1-inhibitor ...The safety data collected included physical examination findings, biochemistry analysis results, and electrocardiogram findings. The study ...
r102 long-term safety and efficacy of oral deucrictibant for ...CHAPTER-1 open-label extension study results provide evidence on long-term safety and efficacy of deucrictibant for HAE attack prevention.
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