KVD900 for Hereditary Angioedema

Not currently recruiting at 68 trial locations

Overseen By KalVista Pharmaceuticals

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: KalVista Pharmaceuticals, Ltd.

Must not be taking: Anti-coagulants, Anti-platelets

Disqualifiers: Bleeding disorders

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: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called KVD900 (also known as sebetralstat) for young people with Hereditary Angioedema (HAE), a rare condition that causes sudden swelling. The goal is to understand how the body processes KVD900 in two different doses, 300 mg and 600 mg. This trial targets adolescents aged 12 to 17 who are already part of another KVD900 study and do not have a history of bleeding disorders. Participants will provide samples and complete forms as part of the trial. As a Phase 3 trial, this is the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking any anti-coagulant or anti-platelet agents.

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

Research shows that KVD900, also known as sebetralstat, is generally well-tolerated. Studies have found it safe and effective for treating hereditary angioedema (HAE), a condition causing sudden swelling. In a study of 377 swelling episodes, early treatment with KVD900 led to milder symptoms, reducing patient discomfort. Another study focused on young children and confirmed its safety for them as well. Additionally, KVD900 is taken orally, offering more convenience than injectable treatments. Overall, evidence suggests KVD900 is safe for use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

KVD900 is unique because it offers a new oral treatment option for hereditary angioedema (HAE), which is typically managed with injectable therapies like C1 inhibitors or bradykinin receptor antagonists. Researchers are excited about KVD900 because it works by inhibiting kallikrein, an enzyme involved in the inflammatory process, which might help prevent attacks more effectively. Additionally, its oral administration could make it more convenient and preferable for patients who currently rely on injections. This potential for ease of use and rapid action makes KVD900 a promising alternative in the treatment landscape for HAE.

What evidence suggests that KVD900 might be an effective treatment for Hereditary Angioedema?

Research has shown that KVD900, also known as sebetralstat, is a promising treatment for hereditary angioedema (HAE), a condition that causes sudden swelling. In earlier studies, patients experienced quick relief from symptoms, typically in just over an hour. Sebetralstat is a small molecule that blocks plasma kallikrein, an enzyme involved in HAE attacks. Studies also indicate that it is effective and safe for treating attacks of all severities and locations in the body. Unlike other treatments requiring injections, KVD900 is taken orally, offering more convenience. This trial will evaluate two different dosages of KVD900, 300 mg and 600 mg, to further assess its effectiveness and safety, potentially revolutionizing the management of HAE attacks. ^{2 3 5 6 7}

Who Is on the Research Team?

Study Director

Principal Investigator

KalVista Pharmaceuticals, Ltd.

Are You a Good Fit for This Trial?

Adolescents aged 12-17 with Hereditary Angioedema (HAE) types I or II can join this trial if they're already in the KVD900-302 study. They must be willing to provide samples, complete forms and diaries, and have consent from a legal representative.

Inclusion Criteria

I am willing to provide samples, complete forms, and follow the study's requirements.

I am between 12 and 17 years old.

Patient is currently participating in KVD900-302

Exclusion Criteria

I have a bleeding disorder or am taking blood-thinning medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive KVD900 to investigate its pharmacokinetic profile

6 weeks

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 how the body processes KVD900, a drug for HAE. It's specifically looking at its pharmacokinetics—how the drug is absorbed, distributed, metabolized, and excreted—in adolescents.

How Is the Trial Designed?

Group I: KVD900 600 mg Experimental Treatment 1 Intervention

Group II: Experimental: 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

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]

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]

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]

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]

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]

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]

In a study involving 12 patients with hereditary angioedema (HAE) and acquired C1-inhibitor deficiency (AAE-C1-INH), Berotralstat was found to significantly reduce the number of angioedema attacks across all patient groups after 6 months of treatment.

Patients reported improved quality of life and angioedema control, with notable decreases in attack frequency and improvements in angioedema quality of life (AE-QoL) and angioedema control test (AECT) scores, indicating Berotralstat's efficacy as a long-term prophylactic treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Retrospective Analysis of Long-Term Prophylaxis with Berotralstat in Patients with Hereditary Angioedema and Acquired C1-Inhibitor Deficiency-Real-World Data. Johnson, F., Stenzl, A., Hofauer, B., et al.[2023]

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]

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. 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 ... 2024;391:32-43. • Early treatment was associated with milder attacks and therefore less morbidity. • Results in a large number of attacks (N=377) ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S009167492102666X

KVD900, an oral on-demand treatment for hereditary ... These phase 1 studies evaluated the PK/PD profile of KVD900, showing that KVD900 rapidly achieves near-complete PKa inhibition and is generally safe and well ...