Alpha-proteinase Inhibitor for Eosinophilic Esophagitis

(ZEEPS Trial)

Recruiting at 1 trial location

Overseen By Regina Yearout

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Children's Hospital Medical Center, Cincinnati

Must not be taking: Anticoagulants, Systemic steroids

Disqualifiers: COPD, IgA deficiency, Cancer, 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

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

Compensation: Varies

Number of Visits: 4

Duration: 4 weeks

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Zemaira, an alpha-proteinase inhibitor, to determine its effectiveness for Eosinophilic Esophagitis (EoE). EoE involves certain cells in the esophagus causing inflammation and swallowing issues. The trial aims to see if Zemaira can reduce these symptoms when other treatments have been insufficient. Suitable candidates for this trial have EoE that hasn't been controlled by standard treatments, such as diet changes or specific medications, for at least 8 weeks. As a Phase 2 trial, this research measures Zemaira's effectiveness in an initial, smaller group, offering a chance to explore new treatment options.

Will I have to stop taking my current medications?

The trial does not require you to stop your current medications if they are stable and related to Eosinophilic Esophagitis. You must keep the same dosage for certain medications like proton pump inhibitors and leukotriene inhibitors during the study.

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

Research shows that Zemaira, a type of protein treatment, has been safe for other health issues. Specifically, studies have demonstrated its safe use in treating alpha1-PI deficiency. Patients received it once a week at the recommended dose, and it was well-tolerated. This suggests it might also be safe for people with eosinophilic esophagitis, a condition where certain white blood cells build up in the esophagus. While the current study examines its safety for this new use, past evidence provides some reassurance about its overall safety in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Eosinophilic Esophagitis?

Most treatments for eosinophilic esophagitis, such as corticosteroids and dietary management, work by reducing inflammation or avoiding allergens. But the alpha-proteinase inhibitor, like Zemaira, works differently by targeting and modulating the activity of proteins that contribute to inflammation. Researchers are excited about this treatment because it offers a novel approach, potentially providing relief by directly addressing the underlying protein imbalances in the esophagus. This could lead to more effective and faster symptom control than current standard treatments.

What evidence suggests that this treatment might be an effective treatment for Eosinophilic Esophagitis?

Research has shown that alpha-proteinase inhibitors, such as Zemaira, are under investigation for their potential to aid in eosinophilic esophagitis (EoE). EoE occurs when certain white blood cells accumulate in the esophagus, causing inflammation and discomfort. Zemaira, the investigational treatment in this trial, blocks proteins responsible for this inflammation. Early findings suggest that Zemaira might reduce these inflammatory cells, potentially relieving symptoms. However, further research is necessary to confirm these early results in humans. ^{1 3 5 6 7}

Who Is on the Research Team?

Marc E Rothenberg, MD, PhD

Principal Investigator

Cincinnati Children's Hospital Medical Center

Are You a Good Fit for This Trial?

Adults aged 18-70 with Eosinophilic Esophagitis (EoE) who've had moderate to severe abdominal/chest pain or swallowing difficulties at least twice a week, and whose symptoms weren't controlled by standard treatments. Participants must be willing to maintain their current diet and medical management for EoE throughout the study.

Inclusion Criteria

Willing and able to comply with study visits and activities

Willing to maintain current dietary regimen throughout the course of the study. Diet must have been stable for 8 weeks prior to baseline endoscopy

My esophagus has inflammation with more than 15 eosinophils per high powered field, not caused by another known condition.

Exclusion Criteria

I do not have Crohn's, inflammatory bowel disease, or Celiac disease.

Known immunoglobulin A (IgA) deficiency (i.e., IgA level < 8 mg/dL at screening)

I am taking blood thinners other than aspirin or NSAIDs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

12 weeks

Treatment

Participants receive weekly intravenous infusions of Zemaira (120 mg/kg body weight) for 4 weeks

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Alpha-proteinase inhibitor

Trial Overview The trial is testing Zemaira (alpha-1 trypsin inhibitor) in patients with Eosinophilic Esophagitis. It's an open-label study, meaning both researchers and participants know what treatment is being given, focusing on how effective this drug is for treating EoE.

How Is the Trial Designed?

Group I: Active Drug Experimental Treatment 1 Intervention

Zemaira alpha-proteinase inhibitor

Alpha-proteinase inhibitor is already approved in United States, European Union for the following indications:

Approved in United States as Aralast for:

• Chronic augmentation therapy in adults with clinically evident emphysema due to severe congenital deficiency of alpha1-proteinase inhibitor (alpha1-antitrypsin deficiency)

Approved in United States as Glassia for:

• Chronic augmentation and maintenance therapy in adults with clinically evident emphysema due to severe hereditary deficiency of alpha1-proteinase inhibitor (alpha1-antitrypsin deficiency)

Approved in United States as Prolastin-C for:

• Chronic augmentation and maintenance therapy in adults with clinical evidence of emphysema due to severe hereditary deficiency of alpha1-proteinase inhibitor (alpha1-antitrypsin deficiency)

Approved in United States as Zemaira for:

• Chronic augmentation therapy in adults with clinically evident emphysema due to severe congenital deficiency of alpha1-proteinase inhibitor (alpha1-antitrypsin deficiency)

Approved in European Union as Alpha-1-proteinase inhibitor for:

• Congenital Alpha1–Proteinase Inhibitor deficiency

Who Is Running the Clinical Trial?

Children's Hospital Medical Center, Cincinnati

Lead Sponsor

Trials

844

Recruited

6,566,000+

CSL Behring

Industry 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

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

The improved purification method for alpha-proteinase inhibitor (PI) from fraction IV-1 paste achieved approximately 90% purity and a yield of 60-70%, making it effective for large-scale production.

This method incorporates advanced techniques like ion exchange chromatography and virus inactivation, ensuring both the safety and efficacy of the alpha 1 PI for potential treatment of congenital emphysema.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Purification of alpha 1 proteinase inhibitor from human plasma fraction IV-1 by ion exchange chromatography. Chen, SX., Hammond, DJ., Lang, JM., et al.[2013]

In a pilot study involving six patients with recalcitrant atopic dermatitis who did not respond to high potency topical steroids, treatment with alpha 1-proteinase inhibitor (alpha 1-PI) led to significant clinical improvement in symptoms like pain and itching within 6 to 21 days.

The therapy was safe, with no adverse side effects reported after 120 days, suggesting that alpha 1-PI may effectively address the imbalance of serine proteases in atopic dermatitis without causing harm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of atopic dermatitis with alpha 1-proteinase inhibitor. Wachter, AM., Lezdey, J.[2004]

Loss of the protein SPINK7 in the esophagus contributes to eosinophilic esophagitis (EoE) by increasing the activity of kallikrein 5 (KLK5), which impairs the barrier function of esophageal cells and leads to inflammation.

Inhibiting KLK5 or its receptor PAR2 shows promise as a potential treatment for EoE, as demonstrated by reduced eosinophilia and cytokine production in both murine models and clinical samples from patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional role of kallikrein 5 and proteinase-activated receptor 2 in eosinophilic esophagitis. Azouz, NP., Klingler, AM., Pathre, P., et al.[2022]

Prolastin-C, a new formulation of alpha1-proteinase inhibitor, showed pharmacokinetic equivalence to the original Prolastin in a study involving 24 subjects, indicating that both products deliver similar levels of the active protein in the bloodstream.

Both treatments had comparable safety profiles, with no significant differences in adverse events or treatment-emergent viral infections, suggesting that Prolastin-C is a safe alternative for patients with alpha1-antitrypsin deficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic comparability of Prolastin®-C to Prolastin® in alpha₁-antitrypsin deficiency: a randomized study. Stocks, JM., Brantly, ML., Wang-Smith, L., et al.[2021]

Prolastin aerosol therapy significantly increased sputum levels of alpha-1 proteinase inhibitor (alpha1-PI) in cystic fibrosis patients, indicating effective delivery of the treatment, with a three-fold increase observed (P = 0.002).

The therapy led to a decrease in sputum taurine levels, which correlates with respiratory exacerbations, suggesting that Prolastin may help reduce airway inflammation in cystic fibrosis without adversely affecting pulmonary function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolastin aerosol therapy and sputum taurine in cystic fibrosis. Cantin, AM., Berthiaume, Y., Cloutier, D., et al.[2013]

Alpha 1-antitrypsin is crucial for protecting the lungs from damage caused by neutrophil elastase, and its deficiency can lead to emphysema, especially in smokers, highlighting the importance of avoiding smoking for affected individuals.

The abnormal Z-mutant form of alpha 1-antitrypsin can accumulate in the liver, leading to serious liver diseases, including cirrhosis and cancer, with liver transplantation being a potential treatment for end-stage liver disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alpha 1-antitrypsin deficiency: an overview. van Steenbergen, W.[2022]

In a randomized, placebo-controlled trial involving 41 adult patients with eosinophilic esophagitis (EoE), montelukast was found to be well tolerated, with no reported side effects.

After 26 weeks, 40% of patients taking montelukast maintained remission from EoE symptoms, but this was not significantly different from the 23.8% remission rate in the placebo group, indicating that montelukast may not be effective for maintaining remission after steroid therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Montelukast Does not Maintain Symptom Remission After Topical Steroid Therapy for Eosinophilic Esophagitis. Alexander, JA., Ravi, K., Enders, FT., et al.[2021]

Alpha 1-proteinase inhibitor (Prolastin) has been used since 1988 as an intravenous treatment for pulmonary emphysema caused by alpha 1-antitrypsin deficiency, although no formal controlled studies have confirmed its efficacy.

Prolastin has a strong safety record and has also been used experimentally for inhalation in cystic fibrosis and to treat panniculitis, but its future may be challenged by newer antiproteases that could offer better administration routes and pricing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alpha 1-antitrypsin augmentation therapy. Sandhaus, RA.[2005]

In a study of 36 adult patients with eosinophilic esophagitis, treatment with mometasone furoate significantly reduced dysphagia symptoms compared to placebo, with a median score reduction of 6.5 versus 0 (p < 0.01).

While mometasone improved dysphagia, it did not show a significant benefit in overall health-related quality of life as measured by two different questionnaires, indicating that while it helps with swallowing difficulties, it may not enhance broader quality of life aspects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topically applied mometasone furoate improves dysphagia in adult eosinophilic esophagitis - results from a double-blind, randomized, placebo-controlled trial. Tytor, J., Larsson, H., Bove, M., et al.[2021]

A new plasma-derived alpha1-Proteinase Inhibitor (Zemaira) was shown to be bioequivalent to the existing treatment (Prolastin) in restoring serum Alpha1-antitrypsin levels in individuals with AAT deficiency, achieving levels above the protective threshold of 11 microM.

The study, involving 44 subjects over a 10-week double-blind phase, found that Zemaira was well tolerated with a lower incidence of treatment-related adverse events (7%) compared to Prolastin (21%), and there were no cases of viral transmission, indicating its safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-center study: the biochemical efficacy, safety and tolerability of a new alpha1-proteinase inhibitor, Zemaira. Stocks, JM., Brantly, M., Pollock, D., et al.[2019]

Eosinophilic esophagitis is a chronic disorder that mimics GERD symptoms but does not respond to anti-GERD treatments; effective management includes dietary restrictions and topical corticosteroids.

Current research is exploring anti-interleukin-5 monoclonal antibodies as a potential treatment, aiming to target the underlying causes of esophageal remodeling and fibrosis associated with the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of pediatric eosinophilic esophagitis: an update. Khan, S.[2021]

In a study of 80 patients with eosinophilic esophagitis, both oral prednisone and swallowed fluticasone were effective in improving esophageal histology and alleviating symptoms, with prednisone showing a greater degree of histologic improvement.

Despite the greater histologic benefits of prednisone, there was no significant difference in symptom resolution or relapse rates between the two treatments, and both groups experienced a high rate of symptom relapse after therapy was stopped, indicating the need for ongoing maintenance treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of oral prednisone and topical fluticasone in the treatment of eosinophilic esophagitis: a randomized trial in children. Schaefer, ET., Fitzgerald, JF., Molleston, JP., et al.[2022]

In vitro tests showed that yeast-derived recombinant alpha(1)-proteinase inhibitor did not directly affect the migration of neutrophils or eosinophils, indicating it does not act as a chemoattractant for these immune cells.

Despite its lack of direct chemotactic effects, the recombinant alpha(1)-proteinase inhibitor may still help maintain antibacterial defenses in patients receiving inhalation therapy, suggesting it has beneficial anti-inflammatory properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunomodulation by alpha(1)-proteinase inhibitor: lack of chemotactic effects of recombinant human alpha(1)-proteinase inhibitor from yeast on human peripheral blood granulocytes. Mosheimer, B., Alzner, R., Wiedermann, CJ.[2021]

Zemaira showed the highest purity and specific activity among the three alpha-1-proteinase inhibitor products tested, indicating it may be the most effective option for treating alpha-1-proteinase deficiency.

Prolastin had the lowest purity and higher levels of inactive A1-PI compared to Zemaira and Aralast, suggesting it may be less effective in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study comparing the purity, functionality and isoform composition of alpha-1-proteinase inhibitor (human) products. Cowden, DI., Fisher, GE., Weeks, RL.[2006]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05485155

NCT05485155 | Zemaira Eosinophilic Esophagitis Pilot Study This is a prospective, open-label drug study that will examine the effects of Zemaira (alpha-1 trypsin inhibitor) in patients with Eosinophilic Esophagitis.

2. cc.nih.gov cc.nih.gov/recruit/protocols/001854-I

An Open-Label Study of Zemaira (Alpha 1-Trypsin Inhibitor ... An Open-Label Study of Zemaira (Alpha 1-Trypsin Inhibitor) in Subjects with Eosinophilic Esophagitis ... Zemaira® to determine its effectiveness in treating EoE.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05485155?term=AREA%5BBasicSearch%5D(zemaira)&rank=3

NCT05485155 | Zemaira Eosinophilic Esophagitis Pilot Study This is a prospective, open-label drug study that will examine the effects of Zemaira (alpha-1 trypsin inhibitor) in patients with Eosinophilic Esophagitis.

4. mdpi.com mdpi.com/1999-4923/17/6/753

Current and Emerging Therapies for Eosinophilic ... Overall, this phase 3 trial demonstrated that weekly dupilumab significantly improved histologic outcomes and alleviated symptoms of EoE in adults and ...

5. cegir.rarediseasesnetwork.org cegir.rarediseasesnetwork.org/research-study/7811

Research Study | Consortium of Eosinophilic Gastrointestinal ... This study is being conducted to determine whether the study drug Zemaira is safe and effective in adults with eosinophilic esophagitis (EoE).

6. withpower.com withpower.com/trial/phase-2-esophagitis-9-2022-dde41

Alpha-proteinase Inhibitor for Eosinophilic Esophagitis Topically applied mometasone furoate improves dysphagia in adult eosinophilic esophagitis - results from a double-blind, randomized, placebo-controlled trial.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2844046/

Alpha1-Proteinase Inhibitor (Human) - PMC Clinical studies have shown Zemaira® to be a safe and effective treatment for alpha1-PI deficiency when administered once weekly at the recommended dose of 60 ...