Long-Term Safety of KVD900 for Hereditary Angioedema

Recruiting at 67 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

145 Participants Needed

Trial Summary

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.

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

Research shows that KVD900, an oral plasma kallikrein inhibitor, has potential as an on-demand treatment for hereditary angioedema, a condition causing episodes of swelling and pain. Similar drugs like sebetralstat have shown promising results in reducing these symptoms in clinical trials. ^{1 2 3 4 5}

What safety data exists for KVD900 (sebetralstat) in humans?

Sebetralstat, also known as KVD900, has shown promising safety results in a phase 2 trial for treating hereditary angioedema, with no serious adverse effects reported. This suggests it is generally safe for human use in the context of this condition. ^{2 3 4 6 7}

What makes the drug KVD900 unique for treating hereditary angioedema?

KVD900 (sebetralstat) is unique because it is designed to be a fast-acting oral treatment specifically for hereditary angioedema, which is a rare condition with limited treatment options. Unlike some other treatments that may require injections, KVD900 offers the convenience of oral administration. ^{8 9 10 11 12}

What is the purpose of this trial?

This trial tests the long-term safety of KVD900 in individuals with HAE. KVD900 aims to reduce symptoms by blocking proteins that cause swelling. Another treatment, Berotralstat, is used to prevent HAE attacks.

Research Team

Study Director

Principal Investigator

KalVista Pharmaceuticals, Ltd.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. 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]

2. 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]

3. 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]

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

Hereditary angioedema outcomes in US patients switched from injectable long-term prophylactic medication to oral berotralstat. [2023]

5. 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]

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

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

7. 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]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Renoprotection Provided by Additional Diuretic Treatment in Partially Nephrectomized Ren-2 Transgenic Rats Subjected to the Combined RAS and ETA Blockade. [2022]

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

Clinical toxicity of furosemide in hospitalized patients. A report from the Boston Collaborative Drug Surveillance Program. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of a 14-day administration of tolvaptan in the treatment of patients with ascites in hepatic oedema. [2018]

11. England pubmed.ncbi.nlm.nih.gov

Long-term bumetanide treatment of patients with edema due to renal disease. Cooperative studies. [2019]

12. England pubmed.ncbi.nlm.nih.gov

Effect of loading dose and formulation on safety and efficacy of conivaptan in treatment of euvolemic and hypervolemic hyponatremia. [2019]