Oral PHA-022121 for Hereditary Angioedema

(HAE CHAPTER-1 Trial)

Recruiting at 35 trial locations

Overseen By Pharvaris Clinical Team

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Pharvaris Netherlands B.V.

Must not be taking: C1-esterase inhibitors, Kallikrein inhibitors

Disqualifiers: Pregnancy, Abnormal ECG, Alcohol abuse, others

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

Compensation: Varies

Number of Visits: Unknown

34 Participants Needed

Trial Summary

What is the purpose of this trial?

This study evaluates the safety and efficacy of PHA-022121 administered orally for prophylaxis against angioedema attacks in patients with hereditary angioedema (HAE). The study consists of 2 parts, with patients completing participation in Part 1 prior to initiation of treatment in Part 2. Part 1 of the study has 3 parallel arms and approximately 30 patients will be equally randomized to one of two dose regimens of PHA-022121 or matching placebo. Patients will continue to the single open-label arm in Part 2 of the study after completion of Part 1. The screening period is up to 8 weeks and the treatment periods are 12 weeks (Part 1) and 30 months (Part 2) in duration.

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.

What evidence supports the effectiveness of the drug PHA-022121 for hereditary angioedema?

Newer therapies for hereditary angioedema, like C1-inhibitors and contact system modulators such as ecallantide and icatibant, have been shown to be effective in treating acute attacks and preventing symptoms, with minimal side effects. These treatments have been validated through placebo-controlled studies, suggesting that similar novel therapies like PHA-022121 may also be effective. ^{1 2 3 4 5}

How is the drug PHA-022121 different from other treatments for hereditary angioedema?

PHA-022121 is an oral treatment for hereditary angioedema, which is unique compared to other treatments that often require subcutaneous or intravenous administration. This oral option could offer more convenience and ease of use for patients. ^{2 4 6 7 8}

Research Team

Marc Riedl, MD

Principal Investigator

UC San Diego, La Jolla, California, United States

Emel Aygören-Pürsün, MD

Principal Investigator

University Hospital Frankfurt - Goethe University, Frankfurt, Germany

Eligibility Criteria

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

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.

Timeline

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

Treatment Details

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.

Participant Groups

Group I: Part 2: Open-label Experimental Treatment 1 Intervention

BID high dose of deucrictibant

Group II: Part 1: Low dose Experimental Treatment 1 Intervention

BID low dose of deucrictibant

Group III: Part 1: High dose Experimental Treatment 1 Intervention

BID high dose of deucrictibant

Group IV: Part 1: Placebo Placebo Group 1 Intervention

BID placebo

Who Is Running the Clinical Trial?

Pharvaris Netherlands B.V.

Lead Sponsor

Trials

7

Recruited

610+

Findings from Research

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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.

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]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of oral kallikrein inhibitor berotralstat for hereditary angioedema. Gao, Y., Hwang, J., Hwang, G., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Current status of implementation of self-administration training in various regions of Europe, Canada and the USA in the management of hereditary angioedema. [2022]

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

Hereditary angiodema: a current state-of-the-art review, VI: novel therapies for hereditary angioedema. [2019]

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

Hereditary angioedema with normal C1 inhibitor in a French cohort: Clinical characteristics and response to treatment with icatibant. [2018]

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

Hereditary angiodema: a current state-of-the-art review, IV: short- and long-term treatment of hereditary angioedema: out with the old and in with the new? [2019]

5. England pubmed.ncbi.nlm.nih.gov

Update on treatment of hereditary angioedema. [2013]

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

Advances in Hereditary Angioedema: The Prevention of Angioedema Attacks With Subcutaneous C1-Inhibitor Replacement Therapy. [2022]

7. Spain pubmed.ncbi.nlm.nih.gov

A review of oral kallikrein inhibitor berotralstat for hereditary angioedema. [2022]

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

Recombinant human C1 esterase inhibitor for hereditary angioedema attacks: A European registry. [2022]