CSL312 for Hereditary Angioedema

Recruiting at 43 trial locations

Overseen By Trial Registration Coordinator

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: CSL Behring

Must not be taking: C1-INH, Androgens, Antifibrinolytics, Monoclonal antibodies

Disqualifiers: Other angioedema, Estrogen contraceptives, 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: Long-term

171 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase 3b study will evaluate long-term safety and efficacy of CSL312 (also known as garadacimab) when administered subcutaneously (SC)

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications. Specifically, you cannot use C1-INH products, androgens, antifibrinolytics, or other small molecule medications for HAE prevention at least 2 weeks before the trial's Run-in Period. Additionally, you must stop using monoclonal antibodies like lanadelumab 3 months before the Run-in Period.

Is garadacimab (CSL312) safe for humans?

Garadacimab (CSL312) has been studied for safety in people with hereditary angioedema, and it is generally considered safe when given as a monthly injection under the skin. ^{1 2 3 4 5}

How is the drug CSL312 (Garadacimab) unique for treating hereditary angioedema?

CSL312 (Garadacimab) is unique because it is a fully human monoclonal antibody that specifically targets and inhibits activated factor XII (FXIIa), a key player in the kallikrein-kinin system responsible for hereditary angioedema attacks. This drug is administered once a month as a subcutaneous injection, offering a novel approach compared to other treatments that may target different parts of the system or require more frequent dosing. ^{1 2 6 7 8}

Research Team

Study Director

Principal Investigator

CSL Behring

Eligibility Criteria

This trial is for males and females aged 12 or older with hereditary angioedema (HAE), who've had at least three HAE attacks in the past three months. Participants must not be pregnant, breastfeeding, or unwilling to use contraception. They can't have other forms of angioedema or have used certain medications like monoclonal antibodies within specific time frames before the study.

Inclusion Criteria

You have not taken the study drug CSL312 for at least 1 month before joining the trial.

I am 12 years old or older.

I have had 3 or more HAE attacks in the last 3 months.

Exclusion Criteria

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

I am pregnant, breastfeeding, or not willing to stop breastfeeding.

I am fertile, sexually active, and not using or unwilling to use birth control during and 30 days after the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CSL312 (Garadacimab) subcutaneously for long-term prophylactic treatment of hereditary angioedema

Long-term

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• CSL312 (Garadacimab)

Trial Overview The trial is testing CSL312 (Garadacimab) given under the skin to see how safe and effective it is over a long period for preventing swelling attacks in people with hereditary angioedema—a condition causing repeated episodes of severe swelling.

Participant Groups

Group I: CSL312 Experimental Treatment 1 Intervention

Fully human immunoglobulin G subclass 4/lambda recombinant inhibitor monoclonal antibody administered subcutaneously

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]

Long-term treatment with lanadelumab significantly improved health-related quality of life (HRQoL) in patients with hereditary angioedema (HAE), with nearly half of rollover patients achieving a clinically meaningful improvement in their quality of life scores.

A high percentage of patients reported controlled disease and excellent treatment response, indicating that lanadelumab not only reduces attack rates but also enhances overall patient satisfaction and productivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term lanadelumab treatment improves health-related quality of life in patients with hereditary angioedema. Lumry, WR., Maurer, M., Weller, K., et al.[2023]

Cinryze (C1-esterase inhibitor) provided significant relief from hereditary angioedema attacks in children, with a median time to relief of 30 minutes compared to 2 hours for placebo, demonstrating its efficacy in acute management.

In prophylaxis, Cinryze reduced the frequency of attacks by about 50%, with the median monthly attack rate dropping from 3.0 to 0.39, indicating its effectiveness in preventing future episodes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nanofiltered C1-esterase inhibitor for the acute management and prevention of hereditary angioedema attacks due to C1-inhibitor deficiency in children. Lumry, W., Manning, ME., Hurewitz, DS., et al.[2013]

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

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]

3. 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]

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

Long-term lanadelumab treatment improves health-related quality of life in patients with hereditary angioedema. [2023]

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

Nanofiltered C1-esterase inhibitor for the acute management and prevention of hereditary angioedema attacks due to C1-inhibitor deficiency in children. [2013]

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

HDX-MS study on garadacimab binding to activated FXII reveals potential binding interfaces through differential solvent exposure. [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

First Analysis of SERPING1 Gene in Patients with Hereditary Angioedema in Colombia Reveals Two Genotypic Variants in a Highly Symptomatic Individual. [2019]

8. England pubmed.ncbi.nlm.nih.gov

A review of kallikrein inhibitor lanadelumab in hereditary angioedema. [2020]