Berotralstat for Pediatric Hereditary Angioedema

(APeX-P Trial)

Recruiting at 16 trial locations

Overseen By BioCryst Pharmaceuticals, Inc.

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: BioCryst Pharmaceuticals

Disqualifiers: Recurrent angioedema, Cardiac death, 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

Compensation: Varies

Number of Visits: Unknown

29 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the pharmacokinetics (PK) and safety of berotralstat to determine the appropriate weight-based dose for pediatric participants 2 to \< 12 years old for prophylactic treatment to prevent attacks of hereditary angioedema (HAE).

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the drug Berotralstat for pediatric hereditary angioedema?

Research shows that Berotralstat is effective in reducing the frequency of hereditary angioedema attacks in adults and adolescents, suggesting it may also be beneficial for children. It is an oral medication that works by inhibiting plasma kallikrein, a protein involved in the swelling attacks. ^{1 2 3 4 5}

Is berotralstat safe for humans?

Berotralstat is generally considered safe for humans, with studies showing it is well tolerated. The most common side effects are mild stomach issues, and serious side effects are rare. ^{1 4 5 6 7}

How is the drug Berotralstat unique for treating hereditary angioedema?

Berotralstat is unique because it is an oral, once-daily medication that inhibits plasma kallikrein, which helps prevent hereditary angioedema attacks. This is different from other treatments that may require injections or more frequent dosing. ^{1 2 4 5 8}

Research Team

Jolanta Bernatoniene, MD

Principal Investigator

Bristol Royal Hospital for Children

Eligibility Criteria

This trial is for children aged 2 to less than 12 with hereditary angioedema (HAE), weighing at least 12 kg, who could benefit from daily oral medication to prevent HAE attacks. It's not for kids with other types of angioedema, a family history of sudden heart death, certain liver issues, abnormal ECGs, or poor kidney function.

Inclusion Criteria

I am a boy or a girl not pregnant or breastfeeding, aged 2 to under 12.

My body weight is at least 12 kg.

In the opinion of the investigator, the participant would benefit from long term oral HAE prophylaxis

Exclusion Criteria

I have been diagnosed with another type of recurring swelling attacks.

A family member has died suddenly from heart issues.

Current participation in any other investigational drug study or received another investigational drug within 30 days of enrollment

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Standard-of-Care Treatment

Participants receive standard-of-care treatment for hereditary angioedema

12 weeks

Berotralstat Treatment

Participants receive berotralstat treatment for prophylaxis of hereditary angioedema attacks

Up to 144 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Berotralstat

Trial Overview The study tests berotralstat in young patients to find the right dose based on their weight and assess its safety. The goal is to see if this drug can help prevent swelling attacks caused by HAE in these children.

Participant Groups

Group I: Berotralstat Experimental Treatment 1 Intervention

Berotralstat administered once daily in 4 dose cohorts determined by participant weight. Cohorts 1 and 2 will enroll in parallel. After 4 participants from Cohort 1 and 2, with ≥ 2 subjects from Cohort 2, have reached Week 2, Cohort 3 will open for enrollment. Cohort 4 will open for enrollment, after ≥ 4 subjects in Cohort 3 have reached Week 2. Prior to dosing Cohort 3 and 4, available PK and safety data will be reviewed to confirm it is safe to proceed and the appropriate weight bands for each. BioCryst will notify sites when Cohorts 3 and 4 are open for enrollment.

Who Is Running the Clinical Trial?

BioCryst Pharmaceuticals

Lead Sponsor

Trials

55

Recruited

4,400+

Findings from Research

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 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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Long-term safety and effectiveness of berotralstat for hereditary angioedema: The open-label APeX-S study. [2021]

2. 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]

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

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]

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

Orladeyo (Berotralstat): A Novel Oral Therapy for the Prevention of Hereditary Angioedema. [2022]

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

Berotralstat (BCX7353) is a novel oral prophylactic treatment for hereditary angioedema: Review of phase II and III studies. [2021]

7. Spain pubmed.ncbi.nlm.nih.gov

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

8. Denmark pubmed.ncbi.nlm.nih.gov

Oral berotralstat for the prophylaxis of hereditary angioedema attacks in patients in Japan: A phase 3 randomized trial. [2021]