Garadacimab for Hereditary Angioedema

Recruiting at 6 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety of switching to a new treatment, garadacimab, for individuals with hereditary angioedema (HAE), a condition causing sudden swelling. It targets those who have used other HAE treatments and will now try garadacimab once a month for about three months. Participants should have a known history of HAE symptoms, such as swelling without an itchy rash, and must have been on a stable dose of HAE medication for at least three months. As a Phase 4 trial, garadacimab is already FDA-approved and proven effective, and this research aims to understand how it benefits more patients.

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 is the safety track record for this treatment?

Research has shown that garadacimab is generally well-tolerated by people with hereditary angioedema (HAE). In studies, participants took garadacimab once a month for over two years, and most did not experience any attacks during this period.

Long-term safety data indicates that garadacimab remains safe for most people, as it did not cause serious side effects even after up to 5.5 years of use. These findings suggest that garadacimab is safe for many individuals with HAE. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Garadacimab is unique because it offers a new approach to treating hereditary angioedema by specifically targeting Factor XIIa, a protein involved in the cascade that triggers swelling attacks. Unlike standard treatments like C1 esterase inhibitors or kallikrein inhibitors, Garadacimab aims to interrupt the process earlier in the pathway, potentially reducing the frequency and severity of attacks with fewer side effects. Researchers are excited about Garadacimab because it could provide a more efficient and targeted option for patients, potentially improving their quality of life with a novel mechanism of action.

What is the effectiveness track record for garadacimab in treating hereditary angioedema?

Studies have shown that garadacimab reduces the number of attacks in people with hereditary angioedema (HAE). Research indicates that garadacimab provides long-lasting protection against these attacks. Additionally, garadacimab maintains a good safety record, even with long-term use. This demonstrates that it is both effective and safe for ongoing treatment. ^{5 6 7 8 9}

Who Is on the Research Team?

Study Director

Principal Investigator

CSL Behring

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

Citations

1. annallergy.org annallergy.org/article/S1081-1206(25)00557-5/fulltext

LONG-TERM INTEGRATED SAFETY AND EFFICACY OF ... These data confirm the favorable long-term safety profile of garadacimab up to 5.5 years of exposure, as well as durable efficacy with sustained protection ...

2. jacionline.org jacionline.org/article/S0091-6749(24)01894-3/fulltext

Garadacimab Real-World Treatment Outcomes Of ... The GREAT study will gather the first real-word data on effectiveness, safety, HRQoL, and HCRU in patients with HAE receiving garadacimab LTP in routine ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39370961/

Long-term safety and efficacy of garadacimab for ... Garadacimab has a favorable safety profile suitable for long-term use and provides durable protection against HAE attacks.

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

Matching-adjusted indirect comparison between ... Results: Compared with lanadelumab 300 Q2W, garadacimab 200 QM statistically significantly reduced number of moderate and/or severe HAE attacks ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT07001280

NCT07001280 | A Study Investigating the Effectiveness ... The primary aim of this study is to investigate the real-world effectiveness of garadacimab as measured by HAE attack rate before and after garadacimab ...

6. thelancet.com thelancet.com/journals/lanhae/article/PIIS2352-3026(24)00081-4/fulltext

Garadacimab for hereditary angioedema attack prevention Garadacimab for hereditary angioedema attack prevention: long-term efficacy, quality of life, and safety data from a phase 2, randomised, open-label extension ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38710185/

Garadacimab for hereditary angioedema attack prevention Once-monthly garadacimab for more than 2 years in patients with hereditary angioedema was well tolerated and efficacious in reducing monthly attack rate and ...

8. jacionline.org jacionline.org/article/S0091-6749(23)02309-6/fulltext

Integrated Safety And Efficacy Of Garadacimab For ... Over a median 1.2 years' observation, the majority of garadacimab-treated patients (94/164, 57.3%) remained attack-free. No placebo-receiving patients (n=25) ...

9. medicalaffairs.cslbehring.com medicalaffairs.cslbehring.com/-/media/medical-affairs/documents/posters/garadacimab/garadacimab_integrated-safety-and-efficacy_slide-deck_csl-medical-affairs.pdf

Integrated safety and efficacy of garadacimab for hereditary ... Integrated safety analysis set: Long-term safety data. Data cut-off: Feb 13, 2023. *Newly enrolled patients received one 400 mg SC loading dose as their ...