CSL312 for Hereditary Angioedema

Recruiting at 12 trial locations

Overseen By Trial Registration Coordinator

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: CSL Behring

Must not be taking: C1-INH, Androgens, Antifibrinolytics, others

Disqualifiers: Other angioedema, Pregnancy, 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

Duration: 12 months

20 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to investigate the safety, PK / PD, and efficacy of SC CSL312 for prophylactic treatment of pediatric subjects with HAE.

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications for hereditary angioedema (HAE) at least 2 weeks before the treatment period starts.

What data supports the effectiveness of the drug CSL312 for hereditary angioedema?

Research shows that garadacimab (CSL312), a new type of drug that blocks a specific protein involved in hereditary angioedema, is being tested for its ability to prevent attacks of this condition. The study aims to see if monthly injections of this drug can safely reduce the frequency of these attacks. ^{1 2 3 4 5}

Is CSL312 (garadacimab) safe for humans?

Garadacimab (CSL312) has been studied for safety in people with hereditary angioedema, and it involves monthly injections. The research indicates it is generally safe for use in humans, but as with any treatment, there may be side effects. ^{1 2 6 7 8}

How is the drug CSL312 different from other treatments for hereditary angioedema?

CSL312, also known as garadacimab, is unique because it is a fully-human monoclonal antibody that targets and inhibits activated factor XII (FXIIa), a key player in the process that leads to hereditary angioedema attacks. Unlike some other treatments, it is administered once a month as a subcutaneous injection, offering a novel approach to preventing these attacks. ^{1 6 7 9 10}

Research Team

Study Director

Principal Investigator

CSL Behring

Eligibility Criteria

This trial is for boys and girls aged 2 to 11 with Hereditary Angioedema (HAE), weighing at least in the 10th percentile for their age. They must have had at least two HAE attacks in the past six months. Kids can't join if they're in another study, have other types of angioedema, are taking certain HAE medications, or plan to have major surgery.

Inclusion Criteria

I am between 2 and 11 years old and my weight is in the healthy range for my age.

I am either male or female.

I have been diagnosed with hereditary angioedema.

Exclusion Criteria

I have been diagnosed with another type of swelling condition besides HAE.

I use medication to prevent swelling attacks due to HAE.

Participation in another interventional clinical study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive subcutaneous CSL312 for prophylactic treatment of hereditary angioedema

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• CSL312

Trial Overview The trial is testing CSL312 given under the skin as a preventive treatment for kids with HAE. It aims to check how safe it is, how the body processes it (pharmacokinetics/PK), and how well it works (pharmacodynamics/PD).

Participant Groups

Group I: CSL312 Experimental Treatment 1 Intervention

Ages 2-5 years and 6-11 years will have specific subcutaneous dosing schedules

Who Is Running the Clinical Trial?

CSL Behring

Lead Sponsor

Trials

204

Recruited

1,207,000+

Dr. Paul McKenzie

CSL Behring

Chief Executive Officer since 2023

PhD in Chemical Engineering from Carnegie Mellon University, B.S. in Chemical Engineering from the University of Pennsylvania

Dr. Bill Mezzanotte

CSL Behring

Chief Medical Officer since 2021

MD from Duke University

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]

Emerging therapies for hereditary angioedema (HAE), including C1 esterase replacement, kallikrein inhibitors, and bradykinin receptor 2 antagonists, have shown promise in phase 1 and phase 2 trials, indicating their potential effectiveness in treating HAE.

The clinical trials are well-designed, being double-blind and placebo-controlled, and they focus on patients with confirmed low C1 inhibitor levels, suggesting a robust approach to developing new treatments for HAE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hereditary angiodema: a current state-of-the-art review, VI: novel therapies for hereditary angioedema. Frank, MM.[2019]

In a study involving 212 patients with hereditary angioedema, lanadelumab significantly reduced the mean attack rate by 87.4%, with patients being attack-free for an average of 97.7% of the treatment days.

The treatment was well-tolerated, with most adverse events being mild and resolving quickly; no serious treatment-related adverse events or deaths were reported, indicating a favorable safety profile for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term prevention of hereditary angioedema attacks with lanadelumab: The HELP OLE Study. Banerji, A., Bernstein, JA., Johnston, DT., et al.[2022]

References

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

Efficacy and safety of garadacimab, a factor XIIa inhibitor for hereditary angioedema prevention (VANGUARD): a global, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. [2023]

2. 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]

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

Quantifying the burden of disease and perceived health state in patients with hereditary angioedema in Sweden. [2022]

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

Hereditary angiodema: a current state-of-the-art review, VI: novel therapies for hereditary angioedema. [2019]

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

Demographic and clinical characteristics of patients with hereditary angioedema in Canada. [2022]

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

Prevention of Hereditary Angioedema Attacks with a Subcutaneous C1 Inhibitor. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Prophylactic use of an anti-activated factor XII monoclonal antibody, garadacimab, for patients with C1-esterase inhibitor-deficient hereditary angioedema: a randomised, double-blind, placebo-controlled, phase 2 trial. [2022]

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

Long-term prevention of hereditary angioedema attacks with lanadelumab: The HELP OLE Study. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

A novel splice site mutation in the SERPING1 gene leads to haploinsufficiency by complete degradation of the mutant allele mRNA in a case of familial hereditary angioedema. [2021]

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

Review of the Manitoba cohort of patients with hereditary angioedema with normal C1 inhibitor. [2022]