CSL312 for Hereditary Angioedema

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CSL312, an experimental drug for children with hereditary angioedema (HAE), a condition causing sudden and severe swelling. Researchers aim to determine if CSL312 is safe and effective as a regular preventative measure (prophylactic treatment) for children. The trial seeks children aged 2 to 11 who have been diagnosed with HAE and have experienced at least two swelling attacks in the last six months. As a Phase 3 trial, this is the final step before FDA approval, offering a chance to contribute to a potential new treatment for 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.

Is there any evidence suggesting that CSL312 is likely to be safe for humans?

Research shows that CSL312, also known as garadacimab, has been tested for safety in individuals aged 12 and older. Studies found that taking garadacimab once a month significantly reduced the number of hereditary angioedema (HAE) attacks compared to a placebo. Importantly, these studies reported that patients generally tolerated the treatment well.

Long-term safety data also indicate that garadacimab remains effective and safe over time. Although specific information for younger children (ages 2-11) is not included in these findings, ongoing research is investigating its safety for them.

Overall, safety results from earlier studies suggest that CSL312 is a promising option for managing HAE, with no major safety concerns reported. ^{1 2 3 4 5}

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

Unlike the standard treatments for hereditary angioedema, which often involve intravenous infusions or oral medications, CSL312 offers a new approach through subcutaneous administration. This means it can be injected just under the skin, potentially making it easier and more convenient to use, especially for young children. Researchers are excited about CSL312 because it targets the same pathway as existing treatments but in a more user-friendly form, which could improve adherence and quality of life for patients.

What evidence suggests that CSL312 might be an effective treatment for hereditary angioedema?

Research has shown that CSL312, also known as garadacimab, can effectively treat hereditary angioedema (HAE). Studies have found that most patients taking garadacimab did not experience HAE attacks over six months. Specifically, one study showed that monthly doses of garadacimab greatly reduced the number of HAE attacks compared to a placebo. Patients also reported significant improvements in their quality of life, measured by a special questionnaire for angioedema. This evidence suggests that CSL312, which participants in this trial will receive, could be a promising option for managing HAE symptoms. ^{6 7 8 9 10}

Who Is on the Research Team?

Study Director

Principal Investigator

CSL Behring

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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).

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11804312/

Long‐term safety and efficacy of garadacimab for ... Patients receiving garadacimab experienced substantial improvements in QoL, measured by the Angioedema Quality of Life questionnaire (AE‐QoL) score, as early as ...

2. newsroom.csl.com newsroom.csl.com/News-Releases?item=123049

CSL's Phase 3 Study Shows First-In-Class Garadacimab ... Majority of patients were attack free during the entire six-month treatment period (61.5%); Study results presented for first time at 2023 ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04656418

NCT04656418 | CSL312 (Garadacimab) in the Prevention ... Male or female ≥ 12 years of age; diagnosed with clinically confirmed C1-INH hereditary angioedema; experience ≥ 3 attacks during the 3 months before screening.

4. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(23)00350-1/abstract

Efficacy and safety of garadacimab, a factor XIIa inhibitor ... Monthly garadacimab administration significantly reduced hereditary angioedema attacks in patients aged 12 years and older compared with placebo and had a ...

5. becarispublishing.com becarispublishing.com/doi/10.57264/cer-2024-0237

Matching-adjusted indirect comparison between ... The primary outcome was time-normalized number of HAE attacks. Secondary efficacy outcomes included time-normalized number of HAE attacks ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04739059

NCT04739059 | Long-term Safety and Efficacy of CSL312 ... An Open-label Study to Evaluate the Long-term Safety and Efficacy of CSL312 (Garadacimab) in the Prophylactic Treatment of Hereditary Angioedema. Conditions.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36868261/

Efficacy and safety of garadacimab, a factor XIIa inhibitor ... Monthly garadacimab administration significantly reduced hereditary angioedema attacks in patients aged 12 years and older compared with placebo and had a ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05819775

Study Details | NCT05819775 | CSL312_3003 Safety and ... 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. Official ...

9. thelancet.com thelancet.com/cms/10.1016/S2352-3026(24)00081-4/attachment/fbfb9e69-178b-4047-bee2-9c84c746e4b5/mmc1.pdf

Supplementary appendix and safety of CSL312 as prophylaxis to prevent hereditary angioedema (HAE). The study consists of a Screening Period, a. Run-in Period, 2 ...

10. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/all.16351

Long‐term safety and efficacy of garadacimab for ... The ongoing phase 3 (VANGUARD) OLE study evaluated the long-term safety and efficacy of garadacimab (FXIIa inhibitor) for HAE prophylaxis.