Sebetralstat for Hereditary Angioedema

(KONFIDENT-KID Trial)

Recruiting at 17 trial locations

Overseen By KalVista Pharmaceuticals

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: KalVista Pharmaceuticals, Ltd.

Must not be taking: ACE inhibitors, Estrogens, CYP3A4 modulators

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 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called sebetralstat (also known as KVD900) for children with hereditary angioedema (HAE), a condition causing sudden and severe swelling. Researchers aim to evaluate the effectiveness of different doses for children with HAE Type I or II. The trial includes three dose groups: 150 mg, 300 mg, and 600 mg. Eligible participants will have experienced at least one HAE attack in the past year and weigh more than 20 kg (about 44 pounds). As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires stopping certain medications, like angiotensin-converting enzyme inhibitors and estrogen-containing medications, before the screening visit. If you're taking strong or moderate CYP3A4 inhibitors or inducers, you may also need to stop those. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Sebetralstat (KVD900) is generally safe for treating hereditary angioedema (HAE). In various studies, patients tolerated Sebetralstat well. Most side effects were mild, such as headaches or slight stomach upset, and were similar to those experienced by people taking a placebo, a harmless pill used for comparison.

Longer studies where patients used Sebetralstat over time found that serious side effects were rare. The treatment appears safe when used as directed, which is crucial for people with HAE because the condition can cause dangerous swelling attacks.

Since this trial is in a late phase, substantial safety data already supports Sebetralstat. This indicates that the treatment has been tested in humans before, with no major safety issues reported. ^{1 2 3 4 5}

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

Sebetralstat (KVD900) is unique because it offers a potentially faster and more convenient approach to managing hereditary angioedema (HAE) attacks. Unlike standard treatments, which often involve injections, Sebetralstat is taken orally, which could make it far easier and quicker for patients to use during an attack. Additionally, Sebetralstat works by inhibiting kallikrein, a key enzyme in the pathway that triggers swelling in HAE, potentially stopping attacks before they fully develop. Researchers are excited because this could mean faster relief for patients and a more practical solution for managing this unpredictable condition.

What evidence suggests that this trial's treatments could be effective for hereditary angioedema?

Research has shown that sebetralstat effectively treats hereditary angioedema (HAE) attacks. In a recent study, patients who took sebetralstat experienced faster relief from HAE symptoms compared to those who took a placebo, a pill with no active medicine. Another study found that sebetralstat is safe and effective when taken as needed, meaning it can be taken at the onset of symptoms. Early results also suggest that it helps people manage their condition better by treating attacks quickly. Sebetralstat could be an important option for those seeking to effectively manage HAE attacks.

In this trial, participants will join different dose groups to evaluate the effectiveness of various sebetralstat dosages. ^{2 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 children aged 2-11 with Hereditary Angioedema (HAE) Types I or II who've had at least one HAE attack in the past year. A parent or guardian must consent, and caregivers need to be able to manage treatment and follow the study's diary requirements.

Inclusion Criteria

I am between 2 and 11 years old.

I have been diagnosed with HAE Type I or II.

I have had at least one hereditary angioedema attack in the past year.

Exclusion Criteria

I have been diagnosed with another type of chronic swelling.

I haven't been in a drug trial for the last 4 weeks.

I have HAE and treatments like bradykinin blockers didn't work well for me.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of KVD900 at 75 mg, 150 mg, or 300 mg

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Sebetralstat (KVD900)

Trial Overview The trial tests three doses of Sebetralstat (KVD900): 75 mg, 150 mg, and 300 mg. It's an open-label study where everyone knows what treatment they're getting, aiming to assess safety, how the body processes the drug, and its effectiveness against HAE.

How Is the Trial Designed?

Group I: 600 mg Dose Group Experimental Treatment 1 Intervention

Patients will take a single 600 mg dose of KVD900.

Group II: 300 mg Dose Group Experimental Treatment 1 Intervention

Patients will take a single 300 mg dose of KVD900.

Group III: 150 mg Dose Group Experimental Treatment 1 Intervention

Patients will take a single 150 mg dose of KVD900.

Sebetralstat (KVD900) is already approved in European Union, United States, Switzerland, United Kingdom for the following indications:

Approved in European Union as Sebetralstat for:

• Hereditary angioedema (HAE) Type I or II

Approved in United States as Sebetralstat for:

• Hereditary angioedema (HAE) Type I or II

Approved in Switzerland as Sebetralstat for:

• Hereditary angioedema (HAE) Type I or II

Approved in United Kingdom as Sebetralstat for:

• Hereditary angioedema (HAE) Type I or II

Who Is Running the Clinical Trial?

KalVista Pharmaceuticals, Ltd.

Lead Sponsor

Trials

12

Recruited

810+

Published Research Related to This Trial

In a 48-week phase 3 trial involving 108 patients with hereditary angioedema, berotralstat significantly reduced the monthly attack rates from an average of 3.06 to 1.06 for the 150 mg dose, demonstrating its effectiveness in HAE prophylaxis.

The treatment was well-tolerated, with most adverse events being mild or moderate, and no serious drug-related side effects reported, indicating a favorable safety profile for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Trial of the Efficacy and Safety of Berotralstat (BCX7353) as an Oral Prophylactic Therapy for Hereditary Angioedema: Results of APeX-2 Through 48 Weeks (Part 2). Wedner, HJ., Aygören-Pürsün, E., Bernstein, J., et al.[2021]

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 24-week phase 3 trial involving 121 patients with hereditary angioedema (HAE), berotralstat significantly reduced the frequency of HAE attacks, with a reduction to 1.31 attacks per month at the 150 mg dose compared to 2.35 attacks per month in the placebo group.

Berotralstat was found to be safe and well tolerated, with no serious drug-related adverse events reported, although some patients experienced mild side effects like abdominal pain and diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral once-daily berotralstat for the prevention of hereditary angioedema attacks: A randomized, double-blind, placebo-controlled phase 3 trial. Zuraw, B., Lumry, WR., Johnston, DT., et al.[2021]

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 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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2213219825008219

Long-term Safety and Effectiveness of Sebetralstat This analysis evaluated long-term safety and effectiveness of sebetralstat in KONFIDENT-S (NCT05505916), an ongoing, 2-year, open-label ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05259917

Study Details | NCT05259917 | A Phase III, Crossover Trial ... This study is a randomized, double-blind, placebo-controlled, phase III, three-way crossover clinical trial evaluating the efficacy and safety of KVD900.

3. nejm.org nejm.org/doi/10.1056/NEJMoa2314192

Oral Sebetralstat for On-Demand Treatment of Hereditary ... We conducted the phase 3 KONFIDENT trial to assess the efficacy and safety of sebetralstat as compared with placebo for the on-demand treatment ...

4. ir.kalvista.com ir.kalvista.com/news-releases/news-release-details/kalvista-pharmaceuticals-presents-new-sebetralstat-data-western

KalVista Pharmaceuticals Presents New Sebetralstat Data ... “These interim results suggest that, if approved, sebetralstat could be a safe and effective oral on-demand treatment for breakthrough attacks, ...

5. kalvista.gcs-web.com kalvista.gcs-web.com/news-releases/news-release-details/kalvista-pharmaceuticals-presents-new-data-highlighting

Release Details - KalVista Pharmaceuticals An oral on-demand treatment like sebetralstat could address key barriers and empower patients to treat earlier to ultimately improve outcomes.”.

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

7. 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 ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05505916

NCT05505916 | An Open-label Extension Trial to Evaluate ... This is an open-label, multicenter extension trial to evaluate the long-term safety of KVD900 in patients who are 12 years or older with HAE type I or II.

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35086692/

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 ...