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

Start Date01 Sep 2024

Sponsor / Collaborator

Children's Hospital & Medical Center

[+2]

NCT05582798 / RecruitingPhase 4IIT

A Proof of Concept Trial of Alpha-1 Antitrypsin Augmentation Therapy in Patients With Bronchiectasis

Double-blind, randomized, cross-over trial involving 20 participants with bronchiectasis.
This trial will make an important contribution to therapeutic development in bronchiectasis by determining whether alpha-1 antitrypsin (AAT) therapy results in reduced airway inflammation and improves neutrophil function.
Patients will be randomly assigned to receive Prolastin-C 120mg/kg (n=10 patients) by weekly intravenous infusions, Prolastin-C 180mg/kg (n=10 patients) by weekly intravenous infusions or placebo (0.9% saline) for a period of 4 weeks, followed by a 3-5 week washout period and a further 4 weeks during which patients will cross-over to receive the alternative therapy.

Start Date01 Nov 2022

Sponsor / Collaborator

University Of Dundee

NCT01700036 / CompletedPhase 2

A Pilot Study of Alpha-1-Antitrypsin (AAT) in Steroid Refractory Acute Graft vs Host Disease

This clinical trial will study the safety and efficacy of using the drug Zemaira, an Alpha 1-Antitrypsin (AAT) medication (also known as an Alpha1-Proteinase Inhibitor [Human]) for the treatment of steroid refractory GVHD.
For bone marrow transplant patients, the most common, serious complication is Graft vs Host Disease (GVHD), which at its most severe is a life-threatening, complication and a significant cause of treatment related death, following stem cell transplantation. GVHD is a major obstacle to the overall success of transplant treatment, a strategy that would otherwise provide the possibility of a cure for patients with blood cancers or severe blood disorders. GVHD primarily affects the skin, gut, and liver of the recipient, and involves the interaction of the recipient's (the host's) cells and tissues with the donor's immune system cells that see the host tissues as foreign, and attack the host's cells resulting in tissue and organ damage.
The severity of acute GvHD ranges from mild to severe, and for patients who don't respond to steroid therapy, the complication is nearly always fatal, either from organ damage or opportunistic infection as a consequence of high dose, steroid treatments.
There is currently no known effective therapy for patients with acute graft vs host disease that's refractory (nonresponsive) to steroid therapy. As stated earlier,the overwhelming majority of these patients may ultimately die from infection. The incidence of acute GvHD that requires intervention, is higher for unrelated donor transplants, the most common treatment option available, and therefore, these patients are at higher risk for treatment related complications from GVHD. Approximately 20,000 unrelated donor transplants are performed each year. The magnitude of this problem then is significant for patients who otherwise might be cured of their blood cancer or disease.

Start Date01 Jul 2013

Sponsor / Collaborator

Rogel Cancer Center: University of Michigan

[+2]

100 Clinical Results associated with Alpha-1-Proteinase Inhibitor (Human)(CSL Behring)

100 Translational Medicine associated with Alpha-1-Proteinase Inhibitor (Human)(CSL Behring)

100 Patents (Medical) associated with Alpha-1-Proteinase Inhibitor (Human)(CSL Behring)

Literatures (Medical) associated with Alpha-1-Proteinase Inhibitor (Human)(CSL Behring)

01 Dec 2023·Pulmonary pharmacology & therapeutics

Evaluation of body weight–based dosing, alternative dosing regimens, and treatment interruptions for α1-proteinase inhibitors and implications on biochemical efficacy in patients with α1-antitrypsin deficiency

Article

Author: Gaurav, Mitali ; Li, Zhaoyang ; Yel, Leman

INTRODUCTION:

The recommended standard dose for α₁-proteinase inhibitor (A1PI) augmentation therapy is 60 mg/kg once-weekly (QW) intravenous (IV) infusions that aim to maintain systemic A1PI levels >11 μM, the biochemical efficacy threshold, in patients with α₁-antitrypsin deficiency (AATD). However, this standard dose may not be optimal for all patients. Body weight-based dosing, alternative dosing regimens, and treatment interruption periods were evaluated using population pharmacokinetic (PopPK) modeling and simulations.

METHODS:

A nonlinear mixed-effects PopPK model with covariate effects was developed using data from 3 clinical studies investigating 60 mg/kg QW IV A1PI infusions in patients with AATD (n = 65) to evaluate A1PI pharmacokinetic (PK) characteristics. Model-based simulations were conducted for predefined body weight categories, alternative dosing regimens (60-180 mg/kg QW or once every 2 weeks [Q2W]), and treatment interruption periods ranging from 3 to 14 days.

RESULTS:

A1PI PK characteristics were well described by a 2-compartment turnover model with zero-order input and linear elimination. Body weight was a statistically significant determinant of variability in central volume of distribution. Model-based simulations suggested that patients with a higher body weight may attain the 11 μM threshold quicker than patients with a lower body weight and that QW dosing was better at maintaining A1PI levels >11 μM, even when higher Q2W doses were administered. Missing a dose for as few as 3 days could result in A1PI levels <11 μM.

DISCUSSION:

Findings suggest that doses higher than 60 mg/kg administered QW might be more clinically beneficial in some patients with AATD, and that body weight should be considered in dose optimization.

01 Sep 2022·Pulmonary therapy

Pharmacokinetics and Biochemical Efficacy of an α1-Proteinase Inhibitor (Aralast NP) in α1-Antitrypsin Deficiency: a Cross-Product Retrospective Comparability Analysis

Article

Author: Franke, Ryan M ; Li, Zhaoyang ; Morris, Denise N ; Yel, Leman

INTRODUCTION:

Augmentation therapy with plasma-derived α₁-proteinase inhibitor (A1PI) products is currently the only approved disease-specific therapy for α₁-antitrypsin deficiency (AATD), a genetic disorder associated with decreased levels of A1PI. Systemic trough levels of A1PI in plasma or serum are widely accepted as a biochemical efficacy endpoint in clinical trials for A1PI products.

METHODS:

Retrospective analyses utilizing data from three clinical studies in patients with AATD were conducted to evaluate the pharmacokinetic(s) (PK) and biochemical efficacy comparability of Aralast NP and two other A1PI augmentation therapies, Aralast and Prolastin. All three A1PI products were administered as either single or multiple 60 mg/kg intravenous infusions. PK and biochemical efficacy comparability analyses were conducted by evaluating antigenic and functional A1PI serum or plasma concentration data from each of the three studies.

RESULTS:

Comparable PK parameters were demonstrated between the three products for antigenic A1PI levels following a single infusion, with baseline-corrected and uncorrected geometric mean ratios for peak and systemic exposure ranging from 89.0% to 99.6%, with 90% confidence intervals within the 80-125% reference interval for bioequivalence. Biochemical efficacy comparability analyses of Aralast and Prolastin after multiple infusions at steady state showed geometric mean ratios for uncorrected and baseline-corrected antigenic and functional A1PI trough concentrations over weeks 8-11, and for individual weeks, that ranged from 75.8% to 106.6%, with the majority of the 90% confidence intervals falling either within the 80-125% interval or in proximity to it. Nonparametric superpositioning at steady state suggested that predicted trough concentrations for Aralast NP were comparable to the observed concentrations for Aralast and Prolastin.

CONCLUSION:

These retrospective analyses provide robust evidence that Aralast NP has biochemical efficacy and PK comparable to that of Aralast and Prolastin, supporting the use of any of these A1PI products for the treatment of patients with AATD.

TRIAL REGISTRATION NUMBERS:

ClinicalTrials.gov identifiers, NCT00242385 and NCT00396006.

01 Jun 2022·Pulmonary pharmacology & therapeuticsQ3 · MEDICINE

Comparative biochemical efficacy analysis of an alpha1-proteinase inhibitor (Glassia®) in patients with alpha-1 antitrypsin deficiency

Q3 · MEDICINE

Article

Author: Franke, Ryan M ; Li, Zhaoyang ; Morris, Denise ; Yel, Leman

Alpha₁-proteinase inhibitor (A1PI) augmentation is the only specific treatment targeting the underlying deficiency in alpha₁-antitrypsin deficiency (AATD). The demonstration of efficacy has been based on maintaining the biochemical surrogate endpoints of plasma antigenic and functional A1PI levels above >11 μM. Here we report a biochemical comparability analysis based on data from a phase 2/3, randomized, double-blind, two-arm study with partial crossover of Glassia® (Baxalta US Inc. Westlake Village, CA, USA) and Prolastin® (Grifols Therapeutics LLC, Research Triangle Park, NC, USA) in patients with AATD (NCT00460096). Patients (N = 50) were randomly assigned in a 2:1 ratio to receive either Glassia (n = 33) or Prolastin (n = 17), respectively. In the present study, data from patients in the per-protocol population (n = 29, Glassia; n = 12, Prolastin) were analyzed. We compared the biochemical efficacy of these two A1PI products at steady state of A1PI in plasma after weekly intravenous administration of A1PI at a dose of 60 mg/kg body weight. For both antigenic and functional A1PI levels, with or without baseline correction, the geometric mean ratios (GMRs) of plasma trough levels (Glassia/Prolastin) over a 6-week period at steady state (Weeks 7-12 post-randomization) were near or above 100%, with the 90% confidence intervals (CIs) contained within the 80%-125% interval. For antigenic A1PI, the GMR (90% CI) was 115.8% (108.1-124.2) for baseline corrected and 114.2% (109.2-119.5) for uncorrected concentrations. For functional A1PI, the GMR (90% CI) was 98.7 (92.5-105.4) for baseline corrected and 107.8% (102.3-113.5) for uncorrected concentrations. In conclusion, the biochemical efficacy of Glassia using the endpoints of plasma antigenic and functional A1PI trough concentrations at steady state was comparable with Prolastin in patients with AATD.

News (Medical) associated with Alpha-1-Proteinase Inhibitor (Human)(CSL Behring)

02 Jan 2024

·www.prnewswire.com

CSL Behring Demonstrates Continued Commitment to Alpha-1 Community with Addition of ZEMAIRA® [Alpha1-Proteinase Inhibitor (Human)] 4- and 5-Gram Vials

- 4- and 5-gram ZEMAIRA® vials may reduce the number of vials necessary for reconstitution, thereby providing convenience and lowering package waste KING OF PRUSSIA, Pa., Jan. 2, 2024 /PRNewswire/ -- CSL Behring, a business unit of global biotechnology leader CSL, today announced the availability of 4- and 5-gram vial sizes for ZEMAIRA® [Alpha1-Proteinase Inhibitor (Human)]. Previously available only in a 1-gram vial, the 4- and 5-gram packaging is significant for the Alpha-1 community as it will streamline the preparation process for ZEMAIRA and reduce waste. ZEMAIRA dosing is weight-based, so a person weighing 183 pounds would require five 1-gram vials. With the 4- and 5-gram vial sizes, healthcare professionals will need to reconstitute fewer ZEMAIRA vials per dose for their patients with Alpha-1. Room temperature storage coupled with the larger vial sizes may also help streamline preparation and administration. "We have been providing ZEMAIRA to the Alpha-1 community for 20 years and are committed to listening and addressing unmet needs through our therapies and patient programs," said Shannen Silvestrini, Director, ZEMAIRA Marketing, CSL Behring. "With the larger vial sizes, we will continue to provide a safe and effective treatment option while potentially making it easier for healthcare professionals to prepare ZEMAIRA for their patients." Lowering the number of vials patients need also positively contributes to CSL's efforts to reduce waste in the supply chain and end-to-end production, which is an area of focus of the Environmental Pillar of CSL's Sustainability Strategy. For more information on ZEMAIRA, please visit . About Alpha1 Antitrypsin Deficiency Alpha1 Antitrypsin (AAT) Deficiency is a hereditary condition that can severely affect a patient's lung function. The condition is marked by a low level or absence of AAT, a natural protein that inhibits neutrophil elastase, thereby preventing destruction of lung tissue. Severe deficiency of AAT is associated with a strong tendency for the development of emphysema, a form of chronic obstructive pulmonary disease (COPD), and can significantly impact everyday life and life expectancy. About ZEMAIRA® ZEMAIRA is a highly purified form of AAT (human) currently approved in the US, Brazil, Mexico, and Puerto Rico, where it is indicated for chronic augmentation and maintenance therapy in adults with Alpha 1 Antitrypsin Deficiency and clinical evidence of emphysema. CSL Behring markets ZEMAIRA as Respreeza® in Europe. Important Safety Information (ISI) Alpha1-Proteinase Inhibitor (Human), ZEMAIRA® is indicated to raise the plasma level of alpha1-proteinase inhibitor (A1-PI) in patients with A1-PI deficiency and related emphysema. The effect of this raised level on the frequency of pulmonary exacerbations and the progression of emphysema have not been established in clinical trials. ZEMAIRA may not be suitable for everyone; for example, people with known hypersensitivity to components used to make ZEMAIRA, those with a history of anaphylaxis or severe systemic response to A1-PI products, and those with certain IgA deficiencies. If you think any of these may apply to you, ask your doctor. Early signs of hypersensitivity reactions to ZEMAIRA include hives, rash, tightness of the chest, unusual breathing difficulty, wheezing, and feeling faint. Immediately discontinue use and consult with physician if such symptoms occur. In clinical studies, the following adverse reactions were reported in at least 5% of subjects receiving ZEMAIRA: headache, sinusitis, upper respiratory infection, bronchitis, fatigue, increased cough, fever, injection-site bleeding, nasal symptoms, sore throat, and swelled blood vessels. Because ZEMAIRA is made from human blood, the risk of transmitting infectious agents, including viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent and its variant (vCJD), cannot be completely eliminated. Please see full prescribing information for ZEMAIRA. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit , or call 1-800-FDA-1088. You can also report side effects to CSL Behring's Pharmacovigilance Department at 1-866-915-6958. About CSL Behring CSL Behring is a global biotherapeutics leader driven by our promise to save lives. Focused on serving patients' needs by using the latest technologies, we discover, develop and deliver innovative therapies for people living with conditions in the immunology, hematology, cardiovascular and metabolic, respiratory, and transplant therapeutic areas. We use three strategic scientific platforms of plasma fractionation, recombinant protein technology, and cell and gene therapy to support continued innovation and continually refine ways in which products can address unmet medical needs and help patients lead full lives. CSL Behring operates one of the world's largest plasma collection networks, CSL Plasma. Our parent company, CSL (ASX:CSL; USOTC:CSLLY), headquartered in Melbourne, Australia, employs 32,000 people, and delivers its lifesaving therapies to people in more than 100 countries. For inspiring stories about the promise of biotechnology, visit CSLBehring.com/Vita and follow us on Twitter.com/CSLBehring. Media Contact Etanjalie Ayala Mobile: +1 610 297 1069 Email: [email protected] SOURCE CSL Behring

Drug Approval

100 Deals associated with Alpha-1-Proteinase Inhibitor (Human)(CSL Behring)

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Indication	Country/Location	Organization	Date
Alpha 1-Antitrypsin Deficiency	US	CSL Behring LLC	08 Jul 2003
Pulmonary Emphysema	US	CSL Behring LLC	08 Jul 2003

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01370018 (CTgov)	Phase 2/3	HIV Infections	4	Zemaira (Alpha-1-Proteinase Inhibitor in HIV)	jehbnqldvc(jxipjtcsfs) = ytsbvmqjxv baydzayvmn (ulgaxlbmuj, zrweahifjb - yayhcprfiz)	-	28 Sep 2021
				Zemaira (Alpha-1-Proteinase Inhibitor)	ztpputapgy(gagviyekww) = acvvaewmdg cvbrlcygvg (ykaqbtzrdx, rxbgbyfekr - vayyqaigun) View more
NCT01700036 (Pubmed \| Circulation) Manual	Phase 2	Acute Graft Versus Host Disease	40	α 1 -Antitrypsin	udxesykqun(ogzxkgogrt) = jrqacruwpu frhccuolhy (fqkaxkuiqh ) View more	Positive	22 Mar 2018
NCT00261833 (CTgov)	Phase 4	Alpha 1-Antitrypsin Deficiency \| Emphysema \| Pulmonary Emphysema	180	Alpha1-proteinase inhibitor (Zemaira®)	txppsjvykb(epkyvhrcog): Difference in lung density(adjusted P15) = 0.618 (95% CI, -0.024 to 1.261), P-Value = 0.029; Difference in lung density(adjusted P15) = 0.740 (95% CI, 0.059 - 1.420), P-Value = 0.017; Difference in lung density(adjusted P15) = 0.478 (95% CI, -0.223 to 1.180), P-Value = 0.090 View more	-	19 Jan 2015
				Placebo (Placebo)

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