CSL312 for Hereditary Angioedema

Not currently recruiting at 47 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CSL312 (also known as garadacimab) for individuals with hereditary angioedema (HAE), a condition that causes sudden swelling. The goal is to assess the safety and effectiveness of CSL312 over a long period. Participants must have been diagnosed with HAE, experienced at least three attacks in the last three months, and have frequent attacks. The study aims to find a better way to manage and prevent these painful and disruptive swelling episodes. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for HAE.

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 there any evidence suggesting that CSL312 (Garadacimab) is likely to be safe for humans?

Research shows that garadacimab, also known as CSL312, has undergone safety testing in people with hereditary angioedema. Studies found that patients generally tolerated garadacimab well. Most side effects were mild, such as injection site reactions or headaches, while serious side effects were rare.

One study provided long-term safety data, indicating that patients did not encounter major safety issues with extended use. This suggests that garadacimab could be a safe option for preventing hereditary angioedema attacks. It is important to remember that while studies show promising results, individual experiences may vary. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Garadacimab (CSL312) is unique because it targets hereditary angioedema by using a novel mechanism. Unlike current treatments, which often focus on bradykinin or C1 inhibitors, Garadacimab is a fully human monoclonal antibody that inhibits plasma kallikrein, a key player in the pathway leading to angioedema attacks. This specific targeting may offer more precise control of symptoms with potentially fewer side effects. Additionally, Garadacimab is administered subcutaneously, which could provide more convenience and ease for patients compared to intravenous options. Researchers are excited because this treatment could represent a new frontier in managing and preventing attacks with greater efficacy and patient comfort.

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

Studies have shown that garadacimab reduces the number of attacks in people with hereditary angioedema (HAE). Research indicates that taking garadacimab once a month significantly decreases these attacks. Patients have used it for over two years with positive results, demonstrating its effectiveness and safety for long-term use. Most people tolerate the treatment well, experiencing no serious side effects. Overall, garadacimab provides lasting protection against HAE attacks, making it a promising option for those with this condition. ^{1 4 5 6 7}

Who Is on the Research Team?

Study Director

Principal Investigator

CSL Behring

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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. 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 ...

2. 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.

3. 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 ...

4. medicalaffairs.cslbehring.com medicalaffairs.cslbehring.com/-/media/medical-affairs/documents/posters/hae/hae_garadacimab-naive-pts-in-phase-3-ole_poster_100091_csl-medical-affairs.pdf

Long-Term Efficacy of Garadacimab for Hereditary ... Long-Term Efficacy of Garadacimab for Hereditary Angioedema in Patients With or Without. Prior Exposure in a Phase 3 Open-Label Extension Study. John ...

5. 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.

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

Garadacimab for hereditary angioedema attack prevention ... safety data for garadacimab in adults with hereditary angioedema. Methods. This global phase 2 study comprised a treatment period 1 (TP1: 12 ...

7. 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 ... HAE, hereditary angioedema. 1. Zanichelli A et al. Expert Opin Emerg ... Integrated safety analysis set: Long-term safety data. Data cut-off: Feb 13 ...