Sebetralstat for Hereditary Angioedema

(KONFIDENT-KID Trial)

Recruiting at 20 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

36 Participants Needed

Trial Summary

What is the purpose of this trial?

KVD900-303 is an open-label, multicenter clinical trial in patients aged 2 to 11 years old with HAE Type I or II.

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.

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

Sebetralstat, an oral plasma kallikrein inhibitor, showed promising results in a phase 2 trial for treating hereditary angioedema attacks, indicating it may effectively reduce swelling episodes. Similar drugs like berotralstat, also a kallikrein inhibitor, have been effective in preventing hereditary angioedema attacks, suggesting a potential benefit of Sebetralstat. ^{1 2 3 4 5}

Research Team

Study Director

Principal Investigator

KalVista Pharmaceuticals, Ltd.

Eligibility Criteria

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.

My caregiver can store, give me my medication, and fill out the treatment diary.

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

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

Treatment Details

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.

Participant Groups

Group I: 75 mg Dose Group Experimental Treatment 1 Intervention

Patients will take a single 75 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 dose.

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+

Findings from Research

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]

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 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]

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 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]

References

1. 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]

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

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

4. United States 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. [2021]

5. United States 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). [2021]