Garadacimab for Hereditary Angioedema

Recruiting at 3 trial locations

Overseen By Trial Registration Coordinator

Age: Any Age

Sex: Any

Trial Phase: Phase 4

Sponsor: CSL Behring

Must be taking: Lanadelumab, Berotralstat, pdC1INH

Must not be taking: Androgens, Antifibrinolytics

Disqualifiers: Other angioedema, Hypersensitivity, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 3 months

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires participants to switch from their current prophylactic HAE treatment to garadacimab. If you are using lanadelumab, berotralstat, or pdC1INH, you must have been on a stable dose for at least 3 months before joining the trial.

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

A study showed that Garadacimab, a new type of medication, can help prevent attacks of hereditary angioedema, a rare condition that causes sudden swelling. This drug works by blocking a specific protein involved in the disease, and it was tested in a large, carefully controlled trial to ensure its safety and effectiveness. ^{1 2 3 4 5}

Is garadacimab safe for humans?

Garadacimab has been studied in clinical trials for hereditary angioedema, and these studies have evaluated its safety in humans. The trials were designed to assess both the effectiveness and safety of garadacimab, indicating that safety data has been collected during these studies. ^{1 5 6 7 8}

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

Garadacimab is unique because it is a fully human monoclonal antibody that targets activated factor XII (FXIIa), a key player in the kallikrein-kinin system, to prevent hereditary angioedema attacks. It is administered once a month as a subcutaneous injection, offering a novel approach compared to other treatments that may require more frequent dosing or target different parts of the system. ^{1 2 4 6 9}

What is the purpose of this trial?

This study is designed to evaluate the safety after switching to garadacimab from another prophylactic hereditary angioedema (HAE) treatment (marketed kallikrein \[KK\] inhibitor or plasma-derived C1-esterase inhibitor \[pdC1INH\]prophylactic) when administered once monthly for approximately 3 months in participants aged greater than or equal to (\>=) 12 years with HAE.

Research Team

Study Director

Principal Investigator

CSL Behring

Eligibility Criteria

This trial is for individuals aged 12 or older with Hereditary Angioedema (HAE), who have been on a stable dose of certain HAE medications for at least 3 months. Participants must have had a positive response to previous HAE treatments and documented low levels of C1-esterase inhibitor or C4-antigen, or specific gene mutations associated with HAE.

Inclusion Criteria

My tests show low levels of C1INH or C4 in my blood.

I've responded well to emergency treatments for sudden HAE attacks.

I have a history of swelling episodes under the skin or in mucous membranes without hives.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants switch to garadacimab from their current prophylactic HAE treatment, administered once monthly

3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Garadacimab

Trial Overview The study tests the safety of Garadacimab as a once-monthly treatment when switching from other prophylactic HAE therapies. It aims to see how well participants do over approximately three months after making the switch.

Participant Groups

Group I: Garadacimab Experimental Treatment 1 Intervention

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

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]

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]

Lanadelumab significantly reduced the monthly attack rate of hereditary angioedema (HAE) from the first dose, with rates of 0.41-0.76 compared to 2.04 for placebo, indicating its strong efficacy in preventing attacks.

The treatment was well-tolerated, with similar rates of adverse events during the initial and later phases of the study, suggesting that lanadelumab is a safe long-term option for HAE management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lanadelumab demonstrates rapid and sustained prevention of hereditary angioedema attacks. Riedl, MA., Maurer, M., Bernstein, JA., et al.[2021]

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. Turkey pubmed.ncbi.nlm.nih.gov

Therapeutic management of hereditary angioedema: past, present, and future. [2022]

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

Hereditary angiodema: a current state-of-the-art review, IV: short- and long-term treatment of hereditary angioedema: out with the old and in with the new? [2019]

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. 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]

6. 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]

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

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

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

Lanadelumab demonstrates rapid and sustained prevention of hereditary angioedema attacks. [2021]

9. England pubmed.ncbi.nlm.nih.gov

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