Long-Term Safety of KVD900 for Hereditary Angioedema

Not currently recruiting at 80 trial locations

Overseen By KalVista Pharmaceuticals

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: KalVista Pharmaceuticals, Ltd.

Must not be taking: Androgens, ACE inhibitors, Estrogens

Disqualifiers: Chronic angioedema, Poor drug response, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Long-term

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial focuses on testing the long-term safety of a drug called KVD900 (also known as sebetralstat) for individuals with hereditary angioedema (HAE), a condition that causes sudden swelling. It evaluates the safety for those with HAE type I or II who have experienced at least two attacks in the past three months. Participants must be able to swallow tablets and maintain a stable dosage if they are on certain ongoing treatments. The trial uses two doses of KVD900 to determine the most effective and safest option. This offers patients the potential benefit of a new treatment while contributing to medical research. As a Phase 3 trial, this study represents the final step before FDA approval, allowing participants to contribute to the potential availability of a new treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before joining. You must stop using ACE inhibitors and estrogen-containing medications at least 7 days before enrolling. If you're on long-term prophylactic treatment, you need to be on a stable dose for at least 3 months (or 6 months for danazol) before enrolling.

Is there any evidence suggesting that KVD900 is likely to be safe for humans?

Research has shown that KVD900, also known as sebetralstat, is generally safe for treating hereditary angioedema (HAE). In studies, participants using sebetralstat reported no major safety issues, and the treatment was well-tolerated across all types and severities of attacks.

Ongoing research indicates that long-term use of sebetralstat remains safe. While short-term side effects are closely monitored, no new safety concerns have emerged. This suggests that sebetralstat could be a reliable option for people with HAE. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for hereditary angioedema?

Unlike the standard treatments for hereditary angioedema, which often involve injections or infusions, KVD900 is an oral medication, making it much more convenient for patients. This drug is a potent and selective plasma kallikrein inhibitor, which helps prevent the painful and potentially dangerous swelling associated with the condition. Researchers are excited about KVD900 because it promises rapid relief, potentially working faster than current options, and it offers a less invasive way for patients to manage their symptoms.

What evidence suggests that KVD900 might be an effective treatment for hereditary angioedema?

Research has shown that KVD900, also known as sebetralstat, effectively manages hereditary angioedema (HAE) attacks. In studies, it provided quick relief from HAE symptoms, with some patients feeling better in just over an hour. The data indicates it works well for different types of attacks, regardless of their location or severity. Sebetralstat prevents swelling by blocking a specific enzyme involved in HAE attacks. Taken as a pill, this treatment is more convenient than traditional injections. Overall, KVD900 has shown promise in safely managing HAE symptoms. Participants in this trial will receive either a 600 mg or 300 mg dose of KVD900 to further evaluate its long-term safety. ^{1 6 7 8 9}

Who Is on the Research Team?

Study Director

Principal Investigator

KalVista Pharmaceuticals, Ltd.

Are You a Good Fit for This Trial?

This trial is for adolescents and adults aged 12 or older with Hereditary Angioedema (HAE) types I or II. Participants must have had at least two HAE attacks in the past three months, be on a stable dose of certain prophylactic treatments if applicable, and able to swallow tablets whole. They should not have any known hypersensitivity to KVD900, poor response to similar therapies, significant organ dysfunction, or be pregnant/breastfeeding.

Inclusion Criteria

Patient provides signed informed consent or assent (when applicable). A parent or legally authorized representative (LAR) must also provide signed informed consent when required

I have been diagnosed with hereditary angioedema type I or II.

I am willing and able to follow all study requirements.

Exclusion Criteria

I have not responded well to certain HAE treatments, as judged by my doctor.

History of substance abuse or dependence that would interfere with the completion of the trial, as determined by the Investigator

My liver function is not within the normal range, or I have other significant health issues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive KVD900 for on-demand treatment of angioedema attacks

Long-term

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• KVD900

Trial Overview The trial is testing the long-term safety of an oral medication called KVD900 at a dose of 600 mg. It's designed for patients who experience angioedema attacks due to HAE. As an open-label extension study, all participants will receive the drug without any placebo comparison.

How Is the Trial Designed?

Group I: KVD900 600 mg Experimental Treatment 1 Intervention

Group II: KVD900 300 mg Experimental Treatment 1 Intervention

KVD900 is already approved in European Union, United States for the following indications:

Approved in European Union as sebetralstat for:

• Hereditary Angioedema (HAE)

Approved in United States as sebetralstat for:

• Hereditary Angioedema (HAE)

Who Is Running the Clinical Trial?

KalVista Pharmaceuticals, Ltd.

Lead Sponsor

Trials

12

Recruited

810+

Published Research Related to This Trial

In a study of 17,068 hospitalized patients, 13.9% received furosemide, primarily for congestive heart failure, indicating its common use in managing cardiovascular conditions.

While 10.1% of furosemide recipients experienced adverse reactions, serious life-threatening effects were rare, suggesting that furosemide is generally safe, especially when potassium supplements are used to mitigate hypokalemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical toxicity of furosemide in hospitalized patients. A report from the Boston Collaborative Drug Surveillance Program. Greenblatt, DJ., Duhme, DW., Allen, MD., et al.[2019]

In a Phase II study involving 34 patients who switched from injectable treatments to oral berotralstat (150 mg daily), the medication was well tolerated with common side effects including vomiting, diarrhea, and upper respiratory infections, each occurring in 11.8% of patients.

Patients experienced low monthly attack rates of hereditary angioedema after switching to berotralstat, with a median attack rate of 0 attacks per month over 12 months, and reported significant improvements in treatment satisfaction, particularly in convenience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hereditary angioedema outcomes in US patients switched from injectable long-term prophylactic medication to oral berotralstat. Riedl, MA., Soteres, D., Sublett, JW., et al.[2023]

Icatibant is a safe and effective treatment for acute attacks of hereditary angioedema in adults, with clinical evidence supporting its use and only 10% of patients needing a second dose.

The most common side effects are mild and localized, such as pain and swelling at the injection site, and no serious adverse reactions have been reported, making it a favorable option for self-administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evidence-based review of the potential role of icatibant in the treatment of acute attacks in hereditary angioedema type I and II. Floccard, B., Hautin, E., Bouillet, L., et al.[2021]

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]

Sebetralstat, an oral plasma kallikrein inhibitor, is being evaluated in a phase 3 trial (KONFIDENT) for its efficacy and safety in treating hereditary angioedema with C1-inhibitor deficiency (HAE-C1-INH), following promising results from a phase 2 trial.

Patient feedback indicated a strong preference for using the Patient Global Impression of Change (PGI-C) as the primary outcome measure, with a rating of 'A Little Better' identified as a meaningful milestone for symptom relief, which aligns with the trial's design to assess treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of patient-reported outcome measures for on-demand treatment of hereditary angioedema attacks and design of KONFIDENT, a phase 3 trial of sebetralstat. Cohn, DM., Aygören-Pürsün, E., Bernstein, JA., et al.[2023]

In a phase 2 trial involving 68 participants with hereditary angioedema, the oral plasma kallikrein inhibitor sebetralstat was found to be well tolerated and significantly increased the time to use conventional treatment for attacks compared to placebo, indicating its efficacy in providing symptom relief.

Sebetralstat rapidly suppressed plasma kallikrein activity, with participants experiencing longer relief from symptoms, as evidenced by a significant increase in time to conventional treatment use (over 12 hours with sebetralstat vs. 8 hours with placebo).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An investigational oral plasma kallikrein inhibitor for on-demand treatment of hereditary angioedema: a two-part, randomised, double-blind, placebo-controlled, crossover phase 2 trial. Aygören-Pürsün, E., Zanichelli, A., Cohn, DM., et al.[2023]

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]

KVD900 is a novel oral small-molecule inhibitor of plasma kallikrein (PKa) that shows rapid and nearly complete inhibition of PKa activity, making it a promising on-demand treatment for hereditary angioedema (HAE).

In clinical trials, KVD900 demonstrated over 95% inhibition of DXS-stimulated PKa activity in individuals with HAE for at least 4 hours post-dose, potentially halting the generation of bradykinin and reversing HAE attacks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological suppression of the kallikrein kinin system with KVD900: An orally available plasma kallikrein inhibitor for the on-demand treatment of hereditary angioedema. Duckworth, EJ., Murugesan, N., Li, L., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9620001/

Sebetralstat (KVD900): A Potent and Selective Small Molecule ... Sebetralstat, a potent, selective, orally bioavailable PKa inhibitor in phase 3 for on-demand treatment of HAE attacks.

2. ir.kalvista.com ir.kalvista.com/news-releases/news-release-details/kalvista-pharmaceuticals-shares-latest-sebetralstat-findings

Release Details –Sebetralstat enabled prompt treatment of laryngeal HAE attacks with median time of 1 hour and 16 minutes to onset of symptom relief–.

3. jaci-inpractice.org jaci-inpractice.org/article/S2213-2198(25)00821-9/fulltext

Interim Analysis of KONFIDENT-S Open-label Extension The reported data show that sebetralstat is an effective and safe treatment option for attacks of all anatomic locations/severity. Participants ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06467084

NCT06467084 | Open-Label Safety, PK, and Efficacy Trial ... Open-Label Safety, Pharmacokinetic, and Efficacy Trial of Sebetralstat (KVD900) in Pediatric Patients (Ages 2-11) With Hereditary Angioedema Type I or II.

5. nejm.org nejm.org/doi/abs/10.1056/NEJMoa2314192

Oral Sebetralstat for On-Demand Treatment of Hereditary ... Approved on-demand treatments for hereditary angioedema attacks need to be administered parenterally, a route of administration that is ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40886933/

Interim Analysis of KONFIDENT-S Open-label Extension Objective: This analysis evaluated long-term safety and effectiveness of sebetralstat in KONFIDENT-S (NCT05505916), an ongoing, 2-year, open- ...

7. kalvista.com kalvista.com/wp-content/uploads/2025/03/ITACA_2025_Pooled-Efficacy-Safety_FINAL_3.18.2025.pdf

Efficacy and Safety of Sebetralstat for On-demand ... Efficacy and Safety of Sebetralstat for On-demand Treatment of Hereditary Angioedema in Pooled Analysis of Placebo-controlled Clinical ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05505916?cond=%22Angioedema,%20Hereditary,%20Type%20I%22&intr=%22Plasma%20Kallikrein%22&viewType=Table&rank=1

An Open-label Extension Trial to Evaluate the Long-term ... Also called a data safety and monitoring board, or DSMB. Early Phase 1 ... Safety continues to be evaluated, and short-term adverse events are studied.

9. kalvista.com kalvista.com/wp-content/uploads/2025/04/EAACI_2024_KONFIDENT-S.Poster_Final.pdf

Interim Analysis of the Open-label KONFIDENT-S Trial • The objective of KONFIDENT-S trial is to assess the safety and effectiveness of long-term use of sebetralstat as an on-demand treatment of ...