Study of INBRX-101 Compared to Plasma-derived A1PI Therapy in Adults With AATD Emphysema

Study Overview
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Brief Summary
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Phase 2 study to compare INBRX-101 to plasma derived A1PI therapy in adults with AATD emphysema

Detailed Description
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This is a Phase 2, Double-Blind, Randomized, Active-Control, Parallel Group Study to Assess the Pharmacokinetics, Pharmacodynamics, Immunogenicity, and Safety of INBRX-101 Compared to Plasma-Derived Alpha1-Proteinase Inhibitor (A1PI) Augmentation Therapy in Adults With Alpha-1 Antitrypsin Deficiency (AATD) Emphysema.

Official Title
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Phase 2, Double-Blind, Randomized, Active-Control, Parallel Group Study to Assess the Pharmacokinetics, Pharmacodynamics, Immunogenicity, and Safety of INBRX-101 Compared to Plasma-Derived Alpha1-Proteinase Inhibitor (A1PI) Augmentation Therapy in Adults With Alpha-1 Antitrypsin Deficiency (AATD) Emphysema

Conditions
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Emphysema, Alpha 1-Antitrypsin Deficiency

Intervention / Treatment
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* Drug: INBRX-101
* Drug: Zemaira


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females 18-80 years of age, inclusive, at the time of screening Diagnosis of AATD Evidence of emphysema secondary to AATD FEV1 of ≥ 30% and ≤ 80% predicted at screening Current non-smoking status. Exclusion Criteria: Receipt of A1PI augmentation therapy within 5 weeks prior to the first dose of study drug Known or suspected allergy to components of INBRX-101, A1PI or human IgG Known selective or severe Immunoglobulin A (IgA) deficiency Known or suspected diagnosis of type 1 diabetes or diagnosed with uncontrolled type 2 diabetes Received IV immunoglobulins, monoclonal antibodies and/or other biologic therapies within 30 days On waiting list for lung or liver transplant Acute respiratory tract infection or COPD exacerbation within 4 weeks prior to or during screening Evidence of decompensated cirrhosis Active cancers or has a history of malignancy within 5 years prior to screening History of unstable cor pulmonale Clinically significant congestive heart failure

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double-blind, randomized, active-control, parallel group interventional study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: INBRX-101 Q3W<br>IV every 3-weeks (Q3W) and placebo (normal saline) | Drug: INBRX-101<br>* A1PI, Recombinant, Bivalent Fc Fusion Protein<br>|
| Experimental: INBRX-101 Q4W<br>IV every 4-weeks (Q4W) and placebo (normal saline) | Drug: INBRX-101<br>* A1PI, Recombinant, Bivalent Fc Fusion Protein<br>|
| Active Comparator: Zemaira (A1PI)<br>60 mg/kg IV once weekly (QW) and placebo (normal saline) | Drug: Zemaira<br>* Alpha1-Proteinase Inhibitor (Human)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum functional AAT (fAAT) levels at steady-state | To assess the mean change in average fAAT concentration as measured by anti-neutrophil elastase capacity [ANEC] from baseline to average serum trough fAAT concentration at steady-state (Ctrough,ss) in patients treated with INBRX-101 compared to A1PI | 32 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| fAAT Concentration changes | Mean change in fAAT concentration from baseline to fAAT average concentration at steady-state (Cavg, ss) in patients treated with INBRX-101 compared to A1PI. | 32 Weeks | 
| Days with fAAT above the lower limit of the normal range | Percentage of days with fAAT above the lower limit of the normal range during steady-state dosing in patients treated with INBRX-101 compared to A1PI. | 32 weeks | 
| Incidence of TEAEs | Incidence of all treatment-emergent adverse events (TEAEs), TEAEs ≥ Grade 3, serious adverse events (SAEs), TEAEs requiring withdrawal from IP treatment, and infusion reactions will be determined. | 32 Weeks | 
| Anti-drug antibodies | Frequency of anti-drug antibodies (ADA) against INBRX-101 and endogenous AAT, as well as neutralizing ADA (NAb) against INBRX-101 and endogenous AAT will be determined. | 32 Weeks | 
| Population Pharmacokinetics: Clearance | Modeling by means of appropriate software to characterize the pharmacokinetic profile of INBRX-101 via estimation of the parameter clearance | 32 Weeks | 
| Population Pharmacokinetics: Volume of Distribution | Modeling by means of appropriate software to characterize the pharmacokinetic profile of INBRX-101 via estimation of the parameter volume of distribution | 32 Weeks | 
| Covariate Analysis: Biometric Values: Weight | Assessment of the impact of patient's weight [in kg] on the pharmacokinetic profile of INBRX-101 | 32 Weeks | 
| Covariate Analysis: Biometric Values: Height | Assessment of the impact of patient's height [in cm] on the pharmacokinetic profile of INBRX-101 | 32 Weeks | 
| Covariate Analysis: Biometric Values: Age | Assessment of the impact of patient's age [in years] on the pharmacokinetic profile of INBRX-101 | 32 Weeks | 
| Covariate Analysis: Biometric Values: Sex | Assessment of the impact of patient's sex [male or female] on the pharmacokinetic profile of INBRX-101 | 32 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AATD, Alpha 1-Antitrypsin Deficiency, Emphysema, INBRX-101, A1PI, AAT