Study of SAR447537 (INBRX-101) Compared to Plasma-derived A1PI Therapy in Adults With AATD Emphysema
- Conditions
- Alpha 1-Antitrypsin DeficiencyEmphysema
- Interventions
- Registration Number
- NCT05856331
- Lead Sponsor
- Sanofi
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 99
- 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.
- Receipt of A1PI augmentation therapy within 5 weeks prior to the first dose of study drug
- Known or suspected allergy to components of SAR447537 (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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description SAR447537 (INBRX-101) Q3W SAR447537 IV every 3-weeks (Q3W) and placebo (normal saline) Zemaira (A1PI) Zemaira 60 mg/kg IV once weekly (QW) and placebo (normal saline) SAR447537 (INBRX-101) Q4W SAR447537 IV every 4-weeks (Q4W) and placebo (normal saline)
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
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
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
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
Trial Locations
- Locations (81)
University of Alabama at Birmingham- Site Number : 105
🇺🇸Birmingham, Alabama, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
St Joseph's Hospital and Medical Center- Site Number : 126
🇺🇸Phoenix, Arizona, United States
St Joseph's Hospital and Medical Center
🇺🇸Phoenix, Arizona, United States
David Geffen School of Medicine- Site Number : 124
🇺🇸Los Angeles, California, United States
David Geffen School of Medicine
🇺🇸Los Angeles, California, United States
UC Davis Comprehensive Cancer Center- Site Number : 110
🇺🇸Sacramento, California, United States
UC Davis Medical Center
🇺🇸Sacramento, California, United States
National Jewish Medical and Research Center- Site Number : 123
🇺🇸Denver, Colorado, United States
National Jewish Medical and Research Center
🇺🇸Denver, Colorado, United States
Western Connecticut Medical Group- Site Number : 119
🇺🇸Danbury, Connecticut, United States
Western Connecticut Medical Group
🇺🇸Danbury, Connecticut, United States
GW Medical Faculty Associates - GW Cancer& Blood Disorders- Site Number : 107
🇺🇸Washington, District of Columbia, United States
University of Florida College of Medicine- Site Number : 101
🇺🇸Gainesville, Florida, United States
University of Florida
🇺🇸Gainesville, Florida, United States
Bruce W. Carter Miami VA Medical Center - NAVREF - PPDS- Site Number : 114
🇺🇸Miami, Florida, United States
University of Miami
🇺🇸Miami, Florida, United States
Pulmonary and Sleep of Tampa Bay- Site Number : 115
🇺🇸Tampa, Florida, United States
Pulmonary and Sleep of Tampa Bay
🇺🇸Tampa, Florida, United States
Cleveland Clinic Florida
🇺🇸Weston, Florida, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Loyola University Medical Center- Site Number : 112
🇺🇸Maywood, Illinois, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
Indiana University Health University Hospital- Site Number : 127
🇺🇸Indianapolis, Indiana, United States
Brigham and Women's Hospital - Lung Center
🇺🇸Boston, Massachusetts, United States
M Health Fairview Clinics and Surgery Center - Minneapolis- Site Number : 125
🇺🇸Minneapolis, Minnesota, United States
M Health Fairview Clinics and Surgery Center - Minneapolis
🇺🇸Minneapolis, Minnesota, United States
Hannibal Regional Healthcare System-HRMG-Hannibal- Site Number : 111
🇺🇸Hannibal, Missouri, United States
Hannibal Clinic
🇺🇸Hannibal, Missouri, United States
Columbia University Irving Medical Center- Site Number : 104
🇺🇸New York, New York, United States
Columbia University
🇺🇸New York, New York, United States
Pulmonary Health Physicians
🇺🇸Syracuse, New York, United States
Oregon Health and Science University- Site Number : 117
🇺🇸Portland, Oregon, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Clinical Research Associates Of Central PA , LLC- Site Number : 128
🇺🇸DuBois, Pennsylvania, United States
Clinical Research Associates Of Central PA , LLC
🇺🇸DuBois, Pennsylvania, United States
Penn State Health Milton S. Hershey Medical Center- Site Number : 122
🇺🇸Hershey, Pennsylvania, United States
Penn State Health Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Temple University Hospital- Site Number : 130
🇺🇸Philadelphia, Pennsylvania, United States
Temple University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Velocity Clinical Research - Spartanburg - PPDS- Site Number : 120
🇺🇸Spartanburg, South Carolina, United States
Velocity Clinical Research - Spartanburg - PPDS
🇺🇸Spartanburg, South Carolina, United States
Houston Methodist Hospital- Site Number : 113
🇺🇸Houston, Texas, United States
Houston Methodist Hospital
🇺🇸Houston, Texas, United States
University of Utah Health
🇺🇸Salt Lake City, Utah, United States
University of Utah Health Care- Site Number : 106
🇺🇸Salt Lake City, Utah, United States
Donna McIntyre
🇦🇺Brisbane, Queensland, Australia
Queensland Centre for Pulmonary Transplantation
🇦🇺Chermside, Queensland, Australia
Investigational Site Number : 204
🇦🇺South Brisbane, Queensland, Australia
Royal Adelaide Hospital
🇦🇺North Adelaide, South Australia, Australia
Eastern Health Clinical School
🇦🇺Box Hill, Victoria, Australia
Investigational Site Number : 207
🇦🇺Box Hill, Victoria, Australia
Investigational Site Number : 203
🇦🇺Fitzroy, Victoria, Australia
St Vincent Hospital Melbourne
🇦🇺Fitzroy, Victoria, Australia
Frankston Hospital
🇦🇺Frankston, Victoria, Australia
Institute for Respiratory Health
🇦🇺Nedlands, Western Australia, Australia
Investigational Site Number : 206
🇦🇺Nedlands, Western Australia, Australia
Investigational Site Number : 201
🇦🇺Adelaide, Australia
Investigational Site Number : 202
🇦🇺Chermside, Australia
Investigational Site Number : 205
🇦🇺Frankston, Australia
Investigational Site Number : 701
🇩🇰Hellerup, Denmark
Investigational Site Number : 702
🇩🇰Vejle, Denmark
NZRSI
🇳🇿Greenlane, Auckland, New Zealand
Investigational Site Number : 403
🇳🇿Auckland, New Zealand
Investigational Site Number : 404
🇳🇿Wellington, New Zealand
P3 Research
🇳🇿Wellington, New Zealand
Investigational Site Number : 801
🇵🇱Warszawa, Mazowieckie, Poland
Investigational Site Number : 802
🇵🇱Kraków, Poland
Investigational Site Number : 901
🇪🇸Santander, Cantabria, Spain
Investigational Site Number : 903
🇪🇸Santiago de Compostela, Spain
Investigational Site Number : 601
🇸🇪Göteborg, Sweden
Ninewells Hospital - PPDS
🇬🇧Dundee, Angus, United Kingdom
Investigational Site Number : 306
🇬🇧Wythenshawe, Cheshire West And Chester, United Kingdom
Medicines Evaluation Unit
🇬🇧Manchester, Cheshire, United Kingdom
Royal Devon and Exeter Hospital (Wonford) - Barrack Rd
🇬🇧Exeter, Devon, United Kingdom
Investigational Site Number : 304
🇬🇧Southampton, Hampshire, United Kingdom
Southampton General Hospital
🇬🇧Southampton, Hampshire, United Kingdom
Investigational Site Number : 302
🇬🇧Birmingham, Warwickshire, United Kingdom
Queen Elizabeth Hospital Birmingham
🇬🇧Birmingham, Warwickshire, United Kingdom
Investigational Site Number : 307
🇬🇧Exeter, United Kingdom