Berotralstat for Pediatric Hereditary Angioedema

(APeX-P Trial)

Not currently recruiting at 19 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called berotralstat to evaluate its effectiveness and safety for children aged 2 to under 12 with hereditary angioedema (HAE), a condition causing sudden swelling. Researchers aim to determine the right dose based on the child's weight to help prevent these swelling attacks. Participants must have a diagnosis of HAE and require long-term oral treatment to prevent frequent swelling episodes. For children meeting these criteria, this trial could be a suitable option. As a Phase 3 trial, it represents the final step before FDA approval, providing a promising opportunity to access a potentially effective treatment.

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.

Is there any evidence suggesting that berotralstat is likely to be safe for humans?

Research shows that berotralstat is generally safe and well-tolerated, reducing the number of hereditary angioedema (HAE) attacks in many patients. Studies, including those involving children, have consistently demonstrated its safety.

Berotralstat is approved for preventing HAE attacks in individuals aged 12 and older, suggesting potential safety for younger children. Long-term studies indicate it remains safe over time. However, its safety for treating sudden HAE attacks has not yet been confirmed.

Overall, current data supports berotralstat's safety for preventing HAE attacks, but more research is needed for its use in children under 12. ^{1 2 3 4 5}

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

Unlike most treatments for hereditary angioedema that focus on acute attack management or use injections, Berotralstat offers a unique approach as an oral, once-daily preventative medication. This makes it more convenient and less invasive compared to the standard injectable therapies. Researchers are excited about Berotralstat because it works by inhibiting plasma kallikrein, which plays a crucial role in the swelling attacks associated with this condition, potentially reducing the frequency and severity of these episodes.

What evidence suggests that berotralstat might be an effective treatment for hereditary angioedema?

Research has shown that berotralstat reduces hereditary angioedema (HAE) attacks in people of all ages, including children. Patients taking berotralstat experience fewer HAE attacks and enjoy a better quality of life. One study found that children had an average of about one attack per month while on berotralstat, compared to more frequent attacks with standard treatment. Taken once daily, this medication has proven safe and effective over the long term. Overall, berotralstat successfully prevents HAE attacks from the start and continues to work well over time. ^{1 2 6 7 8}

Who Is on the Research Team?

Jolanta Bernatoniene, MD

Principal Investigator

Bristol Royal Hospital for Children

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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]

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]

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 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]

Citations

1. ir.biocryst.com ir.biocryst.com/news-releases/news-release-details/biocryst-presents-new-data-long-term-efficacy-and-safety

BioCryst Presents New Data on the Long-term Efficacy and ... —Data across pediatric, adolescent, and adult populations demonstrate sustained reductions in HAE attacks and consistent safety profile—.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40490218/

Long-term safety and efficacy of once-daily berotralstat in ... Treatment with berotralstat led to improvements in HAE attack rates and Angioedema Quality of Life Questionnaire scores up to week 96, with greater improvements ...

3. jacionline.org jacionline.org/article/S0091-6749(24)02316-9/fulltext

HAE Attack Rates in Pediatric Patients 2 to <12 Years ... Median (range) berotralstat dosing duration was 48.1 (12.1-73.0) weeks. Median (range) monthly attack rate in the standard-of-care period was 0.96 (0-5.0).

4. annallergy.org annallergy.org/article/S1081-1206(25)00352-7/fulltext

Oral berotralstat for hereditary angioedema prophylaxis in ... Once-daily oral berotralstat treatment resulted in early and sustained reductions in HAE attack rates, attacks requiring on-demand treatment, ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05453968

Study Details | NCT05453968 | Berotralstat Treatment in ... This is a single-arm, open-label study designed to evaluate the PK and safety of berotralstat weight-based treatment for the prevention of hereditary angioedema ...

6. ir.biocryst.com ir.biocryst.com/news-releases/news-release-details/biocryst-present-new-pediatric-hae-data-american-college-allergy

BioCryst to Present New Pediatric HAE Data at the ... The safety and effectiveness of ORLADEYO for the treatment of acute HAE attacks have not been established.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40716738/

Oral berotralstat for hereditary angioedema prophylaxis in ... Berotralstat is an oral, small-molecule plasma kallikrein inhibitor, approved as prophylaxis of HAE attacks in patients aged 12 years or older.

8. sciencedirect.com sciencedirect.com/science/article/pii/S1081120625002790

Long-term safety and efficacy of once-daily berotralstat in ... This study supports the long-term safety of berotralstat and its efficacy in preventing HAE attacks and improving QoL.