IV C1 Esterase Inhibitor for Hereditary Angioedema

Recruiting at 24 trial locations

Overseen By Patrick M Murphy

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Octapharma

Must not be taking: Androgens, Monoclonal antibodies

Disqualifiers: Pregnancy, B-cell malignancy, Thromboembolic events, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: Single administration per attack

124 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called OCTA-C1-INH (a C1 esterase inhibitor) for individuals with hereditary angioedema (HAE), a condition causing sudden swelling attacks. The trial aims to determine if this treatment can effectively prevent and treat these episodes. Participants will receive either the actual treatment or a placebo (a harmless substance) to compare results. Those who have experienced at least three moderate to severe HAE attacks in the last three months might be suitable for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new treatment.

Will I have to stop taking my current medications?

The trial requires participants to stop certain medications before starting the study. You must not take specific blood products, hormone therapies, and some pain medications for a period ranging from 7 to 14 days before the trial. Please check with the study team for details on your specific medications.

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

Research has shown that C1 esterase inhibitors (C1-INH) are generally safe for treating hereditary angioedema (HAE). In a large international study, patients using C1-INH demonstrated a good safety record, with most handling the treatment well and experiencing few serious side effects. Additionally, C1-INH has proven safe and effective for HAE. Notably, the FDA has already approved this treatment for HAE in other situations, which increases confidence in its safety. Overall, evidence suggests that OCTA-C1-INH is a well-tolerated option for managing HAE. ^{1 2 3 4 5}

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

OCTA-C1-INH is unique because it directly targets the root cause of hereditary angioedema by replenishing C1 esterase inhibitor levels in the body. Unlike current treatments that may focus on managing symptoms or preventing attacks, OCTA-C1-INH provides a more targeted approach by using a purified form of the C1 inhibitor, potentially leading to more effective and rapid relief. Researchers are excited about this treatment because it has the potential to offer a more personalized and efficient solution, reducing the frequency and severity of attacks compared to existing therapies.

What evidence suggests that OCTA-C1-INH might be an effective treatment for hereditary angioedema?

Research has shown that OCTA-C1-INH, which participants in this trial may receive, effectively treats hereditary angioedema (HAE). One study found that it significantly reduced the time for symptom improvement during an HAE attack. Patients who received the C1 esterase inhibitor experienced faster symptom resolution. Long-term evidence indicates that similar treatments, such as HAEGARDA, reduce the frequency of HAE attacks over time. This suggests that OCTA-C1-INH might effectively manage sudden symptoms and prevent future attacks. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals with a confirmed diagnosis of Hereditary Angioedema (HAE) types I or II. Participants must have had multiple HAE attacks in recent months and have specific levels of C1-INH activity and C4 antigen. They should agree to follow study procedures, use certain contraceptives if applicable, and be at least 18 years old for phase one or at least 2 years old for phase two.

Inclusion Criteria

I have been diagnosed with HAE type I or II.

I am willing and able to follow all study rules and attend all appointments.

I've had 3 or more severe HAE attacks in the last 3 months, or if I'm between 2-12 years old, at least 1 in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either OCTA-C1-INH or placebo injection after the first qualifying attack for the treatment and pre-procedure prevention of acute hereditary angioedema attacks

Single administration per attack

1 visit (in-person) per attack

Follow-up

Participants are monitored for symptom relief and response to treatment after injection

4 hours post-injection

Continuous monitoring for 4 hours

Long-term follow-up

Participants are monitored for long-term safety and effectiveness

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• OCTA-C1-INH

Trial Overview The trial is testing an intravenous treatment called OCTA-C1-INH against a placebo to see if it's effective and safe in treating acute hereditary angioedema attacks. It's a phase 3 study where participants are randomly assigned to receive either the real medication or a placebo in different groups without knowing which they're getting.

How Is the Trial Designed?

Group I: OCTA-C1-INH Experimental Treatment 1 Intervention

OCTA-C1-INH injection, 20IU/kg BW after first qualifying attack. Treatment to be administered to blinded as well as open-label subjects.

Group II: Placebo Placebo Group 1 Intervention

0.1 mL/kg BW 0.9% sodium chloride solution injection after first qualifying attack. Only blinded subjects to receive.

OCTA-C1-INH is already approved in United States, European Union for the following indications:

Approved in United States as Berinert for:

• Acute abdominal, facial, or laryngeal hereditary angioedema (HAE) attacks

Approved in United States as Cinryze for:

• Routine prophylaxis against angioedema attacks in adolescent and adult patients with HAE

Approved in United States as Haegarda for:

• Routine prophylaxis to prevent Hereditary Angioedema (HAE) attacks in patients 6 years of age and older

Approved in European Union as C1 Esterase Inhibitor (Human) for:

• Hereditary Angioedema (HAE)

Who Is Running the Clinical Trial?

Octapharma

Lead Sponsor

Trials

86

Recruited

11,300+

Wolfgang Marguerre

Octapharma

Chief Executive Officer since 1983

MBA from INSEAD

Wolfgang Frenzel

Octapharma

Chief Medical Officer since 2010

MD from University of Vienna

Published Research Related to This Trial

Administering C1 esterase inhibitor (C1-INH) concentrate within 6 hours of the onset of a hereditary angioedema (HAE) attack significantly improves the speed of symptom relief and complete resolution compared to treatment after 6 hours, as shown in a post hoc analysis of two studies involving C1-INH.

The analysis indicated that early treatment resulted in a hazard ratio of 3.36 for symptom relief and 4.30 for complete resolution, reinforcing the recommendation for prompt treatment of HAE attacks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of time to treatment on response to C1 esterase inhibitor concentrate for hereditary angioedema attacks. Craig, TJ., Rojavin, MA., Machnig, T., et al.[2013]

A retrospective analysis of 97 patients treated with plasma-derived C1-INH (Berinert) for acute hereditary angioedema attacks revealed a mean half-life of 32.7 hours, indicating prolonged therapeutic effects.

The long half-life of pC1-INH concentrate suggests it may offer extended protection against edema attacks, even after symptoms have resolved, compared to other treatments with shorter durations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population pharmacokinetics of plasma-derived C1 esterase inhibitor concentrate used to treat acute hereditary angioedema attacks. Bernstein, JA., Ritchie, B., Levy, RJ., et al.[2011]

In a phase III study involving 74 patients with hereditary angioedema (HAE), treatment with recombinant human C1 esterase inhibitor (rhC1INH) did not result in any thrombotic or thromboembolic events, indicating its safety for acute attack management.

Elevated plasma D-dimer levels were observed in 80% of patients during acute HAE attacks, especially in those with submucosal symptoms, but these levels decreased by Day 7 post-treatment, suggesting that rhC1INH effectively manages acute symptoms without increasing the risk of deep vein thrombosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elevated D-dimers in attacks of hereditary angioedema are not associated with increased thrombotic risk. Reshef, A., Zanichelli, A., Longhurst, H., et al.[2018]

In a study of 28 patients with hereditary angioedema (HAE) with normal C1-INH, Berinert® was found to be effective in treating acute attacks, with 22 out of 38 assessed attacks showing improvement within 60 minutes of treatment.

No severe adverse effects were reported, indicating that Berinert® is a safe treatment option for patients with HAE, including those with F12 gene mutations or unknown origins.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hereditary angioedema with normal C1 inhibitor: clinical characteristics and treatment response with plasma-derived human C1 inhibitor concentrate (Berinert®) in a French cohort. Bouillet, L., Boccon-Gibod, I., Gompel, A., et al.[2017]

In a long-term study involving 126 patients with hereditary angioedema, subcutaneous human C1-esterase inhibitor (C1-INH[SC]) demonstrated a strong safety profile, with low incidence of adverse events and effective prophylaxis against angioedema attacks over an average treatment duration of 1.5 years.

Patients receiving the higher dose of 60 IU/kg experienced a significant reduction in attack rates, with 83% of those treated for over 2 years remaining attack-free, highlighting the efficacy of C1-INH(SC) as a long-term treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Outcomes with Subcutaneous C1-Inhibitor Replacement Therapy for Prevention of Hereditary Angioedema Attacks. Craig, T., Zuraw, B., Longhurst, H., et al.[2020]

A study involving 20 adults with hereditary angioedema showed that the new C1-INH concentrate has pharmacokinetic parameters similar to existing treatments, indicating it is likely effective for managing the condition.

The new C1-INH demonstrated a favorable safety profile, with no serious adverse events or thromboembolic events reported, suggesting it is well tolerated in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasma-derived C1 esterase inhibitor pharmacokinetics and safety in patients with hereditary angioedema. Martinez-Saguer, I., Bork, K., Latysheva, T., et al.[2023]

Home therapy with human plasma-derived C1-esterase inhibitor (pC1-INH) significantly reduced the mean annual hospitalization days for pediatric patients with hereditary angioedema (HAE) from 3.8 to 0.11, indicating improved management of acute edema attacks.

The time from the onset of an attack to treatment administration decreased from 67.5 minutes to 15 minutes, and the time to initial symptom relief improved from 60 minutes to 40 minutes, demonstrating the efficacy and safety of pC1-INH in home settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Home therapy with intravenous human C1-inhibitor in children and adolescents with hereditary angioedema. Kreuz, W., Rusicke, E., Martinez-Saguer, I., et al.[2017]

C1-INH administered subcutaneously (C1-INH(SC)) at 60 IU/kg twice weekly significantly reduced the number of hereditary angioedema (HAE) attacks compared to C1-INH given intravenously (C1-INH(IV)) at 1000 U twice weekly, with a difference of 1.3 attacks per month (P=0.034).

The percentage of patients experiencing substantial reductions in monthly HAE attack rates (≥50%, ≥70%, and ≥90%) was significantly higher with C1-INH(SC) compared to C1-INH(IV), indicating that C1-INH(SC) may be a more effective option for routine prevention of HAE attacks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indirect comparison of intravenous vs. subcutaneous C1-inhibitor placebo-controlled trials for routine prevention of hereditary angioedema attacks. Bernstein, JA., Li, HH., Craig, TJ., et al.[2022]

C1 esterase inhibitor (Berinert®) is effective in treating severe angioedema, not just from hereditary causes but also from angiotensin-converting enzyme inhibitors (ACEIs), as demonstrated in a case study.

The successful treatment of a life-threatening angioedema episode with Berinert® highlights its potential as a therapeutic option for patients experiencing angioedema due to ACEIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Angiotensin-converting enzyme inhibitors-induced angioedema treated by C1 esterase inhibitor concentrate (Berinert®): about one case and review of the therapeutic arsenal. Lipski, SM., Casimir, G., Vanlommel, M., et al.[2020]

Recombinant human C1-esterase inhibitor (rhC1-INH) effectively manages acute hereditary angioedema (HAE) attacks in adolescents, with symptom relief beginning within 19 to 78.5 minutes after administration, based on a study involving 16 adolescents.

The treatment is well tolerated, showing no severe adverse events or hypersensitivity reactions, and successfully restored functional plasma C1-esterase inhibitor levels to normal in nearly all patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant Human C1-Esterase Inhibitor to Treat Acute Hereditary Angioedema Attacks in Adolescents. Baker, JW., Reshef, A., Moldovan, D., et al.[2018]

A registry study involving 135 subjects and 3196 infusions of the C1-inhibitor concentrate Berinert confirmed its extensive safety profile, with only 0.09 adverse events per infusion and minimal related complications.

Only two thromboembolic events were reported, both in patients with existing prothrombotic risk factors, indicating that Berinert is not an independent risk factor for such events when used for treating hereditary angioedema.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of C1-esterase inhibitor in acute and prophylactic therapy of hereditary angioedema: findings from the ongoing international Berinert patient registry. Busse, P., Bygum, A., Edelman, J., et al.[2015]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/19767078/

Efficacy of human C1 esterase inhibitor concentrate ... The primary outcome was time from start of treatment to onset of symptom relief. Secondary outcomes were time to complete resolution, proportion of patients ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06361537

Study of IV Human Plasma-derived C1 Esterase Inhibitor ... The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure.

3. haegarda.com haegarda.com/hcp/efficacy

HAEGARDA | Efficacy Long-term studies have shown the effectiveness HAEGARDA has on reducing HAE attacks over time. Learn about pivotal studies and results for HAEGARDA.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10684372/

Plasma-derived C1 esterase inhibitor pharmacokinetics and ... We investigated the pharmacokinetics and safety profile of new C1-INH in people with hereditary angioedema during an attack-free period.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT01912456

NCT01912456 | A Study to Evaluate the Clinical Efficacy ... The aim of this study is to assess the efficacy of C1-esterase inhibitor in preventing hereditary angioedema attacks when it is administered under the skin ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2213219816301283

Safety and Usage of C1-Inhibitor in Hereditary Angioedema This large, international, registry of patients using C1-INH is the most extensive of its kind, providing real-world data regarding general safety and ...

7. mayoclinic.org mayoclinic.org/drugs-supplements/c1-esterase-inhibitor-human-intravenous-route-subcutaneous-route/description/drg-20072383

C1 esterase inhibitor, human (intravenous route ... C1 esterase inhibitor is used to treat or prevent hereditary angioedema (HAE). ... Safety and efficacy have been established. Appropriate ...

8. cinryze.com cinryze.com/hcp/about

CINRYZE® Information for Healthcare Professionals CINRYZE was the first C1 esterase inhibitor (C1-INH) approved by the FDA for routine prophylaxis of hereditary angioedema (HAE) attacks in adults, adolescents, ...