KVD900 for Hereditary Angioedema

Recruiting at 52 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

12 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug KVD900 for hereditary angioedema?

Research shows that KVD900, an oral plasma kallikrein inhibitor, has promising potential as an on-demand treatment for hereditary angioedema, as it helps control the swelling and pain associated with the condition. ^{1 2 3 4 5}

Is KVD900 (sebetralstat) safe for humans?

Sebetralstat, also known as KVD900, is being tested for safety in a phase 3 trial for hereditary angioedema, and earlier trials have shown promising safety results. While specific safety data for KVD900 is limited, similar drugs like berotralstat have shown mild to moderate side effects, mostly related to the stomach, with minimal serious issues reported. ^{1 5 6 7 8}

What is the purpose of this trial?

This trial is testing a medication called KVD900 in teenagers with a rare condition that causes sudden swelling. The goal is to see how the medication behaves in their bodies and if it can help manage their symptoms.

Research Team

Study Director

Principal Investigator

KalVista Pharmaceuticals, Ltd.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. England 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. [2023]

2. 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]

3. Germany pubmed.ncbi.nlm.nih.gov

Social costs of icatibant self-administration vs. health professional-administration in the treatment of hereditary angioedema in Spain. [2021]

4. England 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. [2022]

5. England 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. [2023]

6. Spain pubmed.ncbi.nlm.nih.gov

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

7. New Zealand 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. [2021]

8. United States 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. [2023]