Alpha 1-Antitrypsin Deficiency, Emphysema
Conditions
Keywords
AATD, Alpha 1-Antitrypsin Deficiency, Emphysema, SAR447537, INBRX-101, A1PI, AAT
Brief summary
Phase 2 study to compare SAR447537 (INBRX-101) to plasma derived A1PI therapy in adults with AATD emphysema
Detailed description
This is a Phase 2, Double-Blind, Randomized, Active-Control, Parallel Group Study to Assess the Pharmacokinetics, Pharmacodynamics, Immunogenicity, and Safety of SAR447537 (INBRX-101) Compared to Plasma-Derived Alpha1-Proteinase Inhibitor (A1PI) Augmentation Therapy in Adults With Alpha-1 Antitrypsin Deficiency (AATD) Emphysema.
Interventions
DRUGSAR447537
A1PI, Recombinant, Bivalent Fc Fusion Protein
DRUGZemaira
Alpha1-Proteinase Inhibitor (Human)
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Double-blind, randomized, active-control, parallel group interventional study
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Males or females 18-80 years of age, inclusive, at the time of screening 2. Diagnosis of AATD 3. Evidence of emphysema secondary to AATD 4. FEV1 of ≥ 30% and ≤ 80% predicted at screening 5. Current non-smoking status.
Exclusion criteria
1. Receipt of A1PI augmentation therapy within 5 weeks prior to the first dose of study drug 2. Known or suspected allergy to components of SAR447537 (INBRX-101), A1PI or human IgG 3. Known selective or severe Immunoglobulin A (IgA) deficiency 4. Known or suspected diagnosis of type 1 diabetes or diagnosed with uncontrolled type 2 diabetes 5. Received IV immunoglobulins, monoclonal antibodies and/or other biologic therapies within 30 days 6. On waiting list for lung or liver transplant 7. Acute respiratory tract infection or COPD exacerbation within 4 weeks prior to or during screening 8. Evidence of decompensated cirrhosis 9. Active cancers or has a history of malignancy within 5 years prior to screening 10. History of unstable cor pulmonale 11. Clinically significant congestive heart failure
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum functional AAT (fAAT) levels at steady-state | 32 Weeks | 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 participants treated with SAR447537 compared to A1PI |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Days with fAAT above the lower limit of the normal range | 32 weeks | Percentage of days with fAAT above the lower limit of the normal range during steady-state dosing in participants treated with SAR447537 compared to A1PI. |
| Incidence of TEAEs | 32 Weeks | Incidence of all treatment-emergent adverse events (TEAEs), TEAEs ≥ Grade 3, serious adverse events (SAEs), TEAEs leading to IMP discontinuation, adverse events of special interest (AESI) (including infusion- related reactions). |
| Anti-drug antibodies | 32 Weeks | Frequency of anti-drug antibodies (ADA) against SAR447537 and endogenous AAT, as well as neutralizing ADA (NAb) against SAR447537 and endogenous AAT. |
| Population Pharmacokinetics: Clearance | 32 Weeks | Modeling by means of appropriate software to characterize the pharmacokinetic profile of SAR447537 via estimation of the parameter clearance |
| fAAT Concentration changes | 32 Weeks | Mean change in serum fAAT concentration from baseline to fAAT average concentration at steady-state (Cavg, ss) in participants treated with SAR447537 compared to A1PI. |
| Covariate Analysis: Biometric Values: Weight | 32 Weeks | Assessment of the impact of participant's weight \[in kg\] on the pharmacokinetic profile of SAR447537 |
| Covariate Analysis: Biometric Values: Height | 32 Weeks | Assessment of the impact of participant's height \[in cm\] on the pharmacokinetic profile of SAR447537 |
| Covariate Analysis: Biometric Values: Age | 32 Weeks | Assessment of the impact of participant's age \[in years\] on the pharmacokinetic profile of SAR447537 |
| Covariate Analysis: Biometric Values: Sex | 32 Weeks | Assessment of the impact of participant's sex \[male or female\] on the pharmacokinetic profile of SAR447537 |
| Population Pharmacokinetics: Volume of Distribution | 32 Weeks | Modeling by means of appropriate software to characterize the pharmacokinetic profile of SAR447537 via estimation of the parameter volume of distribution |
Countries
Australia, Denmark, New Zealand, Poland, Spain, Sweden, United Kingdom, United States
Outcome results
None listed