Study of SAR447537 (INBRX-101) Compared to Plasma-derived A1PI Therapy in Adults With AATD Emphysema (ELEVAATE)

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

Phase 2 study to compare SAR447537 (INBRX-101) to plasma derived A1PI therapy in adults with AATD emphysema

Study Overview

• Status: Completed
• Conditions: Emphysema; Alpha 1-Antitrypsin Deficiency
• Intervention / Treatment: Drug: Zemaira; Drug: SAR447537

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.

• Study Type: Interventional
• Enrollment (Actual): 99
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia, 5000
    • Investigational Site Number : 201
  • Chermside, Australia, 4032
    • Investigational Site Number : 202
  • Queensland
    • Brisbane, Queensland, Australia, 2650
      • Donna McIntyre
    • Chermside, Queensland, Australia
      • Queensland Centre for Pulmonary Transplantation
  • South Australia
    • North Adelaide, South Australia, Australia, 5065
      • Royal Adelaide Hospital
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Eastern Health Clinical School
    • Fitzroy, Victoria, Australia, 3065
      • Investigational Site Number : 203
    • Fitzroy, Victoria, Australia
      • St Vincent Hospital Melbourne
    • Frankston, Victoria, Australia, 3199
      • Frankston Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Institute for Respiratory Health
    • Nedlands, Western Australia, Australia, 6009
      • Investigational Site Number : 206
• Denmark
  • Hellerup, Denmark, 2900
    • Investigational Site Number : 701
  • Vejle, Denmark, 7100
    • Investigational Site Number : 702
• New Zealand
  • Auckland, New Zealand, 1051
    • Investigational Site Number : 403
  • Wellington, New Zealand, 6021
    • P3 Research
  • Wellington, New Zealand, 6021
    • Investigational Site Number : 404
  • Auckland
    • Greenlane, Auckland, New Zealand, 1051
      • NZRSI
• Poland
  • Kraków, Poland, 30-688
    • Investigational Site Number : 802
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 01-138
      • Investigational Site Number : 801
• Spain
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Investigational Site Number : 901
  • La Coruña
    • Santiago de Compostela, La Coruña, Spain, 15706
      • Investigational Site Number : 903
• Sweden
  • Göteborg, Sweden, 413 46
    • Investigational Site Number : 601
• United Kingdom
  • Angus
    • Dundee, Angus, United Kingdom, DD1 9SY
      • Ninewells Hospital - PPDS
  • Cheshire
    • Manchester, Cheshire, United Kingdom, M23 9QZ
      • Medicines Evaluation Unit
  • Cheshire West And Chester
    • Wythenshawe, Cheshire West And Chester, United Kingdom, M23 9QZ
      • Investigational Site Number : 306
  • Warwickshire
    • Birmingham, Warwickshire, United Kingdom, B15 2WB
      • Investigational Site Number : 302
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • University of Alabama at Birmingham
    • Birmingham, Alabama, United States, 35233-2110
      • University of Alabama at Birmingham- Site Number : 105
  • Arizona
    • Phoenix, Arizona, United States, 85013-4220
      • St Joseph's Hospital and Medical Center- Site Number : 126
    • Phoenix, Arizona, United States, 85013-4220
      • St Joseph's Hospital and Medical Center
  • California
    • Los Angeles, California, United States, 90095
      • David Geffen School of Medicine
    • Los Angeles, California, United States, 90095-3075
      • David Geffen School of Medicine- Site Number : 124
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
    • Sacramento, California, United States, 95817
      • UC Davis Comprehensive Cancer Center- Site Number : 110
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Medical and Research Center
    • Denver, Colorado, United States, 80206-2761
      • National Jewish Medical and Research Center- Site Number : 123
  • Connecticut
    • Danbury, Connecticut, United States, 06810
      • Western Connecticut Medical Group
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida College of Medicine- Site Number : 101
    • Miami, Florida, United States, 33136
      • University of Miami
    • Miami, Florida, United States, 33125-1624
      • Bruce W. Carter Miami VA Medical Center - NAVREF - PPDS- Site Number : 114
    • Tampa, Florida, United States, 33607-6316
      • Pulmonary and Sleep of Tampa Bay- Site Number : 115
    • Tampa, Florida, United States, 33607
      • Pulmonary and Sleep of Tampa Bay
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center- Site Number : 112
  • Indiana
    • Indianapolis, Indiana, United States, 46202-5128
      • Indiana University
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455-4800
      • M Health Fairview Clinics and Surgery Center - Minneapolis- Site Number : 125
    • Minneapolis, Minnesota, United States, 55455-4800
      • M Health Fairview Clinics and Surgery Center - Minneapolis
  • Missouri
    • Hannibal, Missouri, United States, 63401
      • Hannibal Clinic
    • Hannibal, Missouri, United States, 63401-6890
      • Hannibal Regional Healthcare System-HRMG-Hannibal- Site Number : 111
  • New York
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center- Site Number : 104
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University- Site Number : 117
  • Pennsylvania
    • DuBois, Pennsylvania, United States, 15801-2277
      • Clinical Research Associates Of Central PA , LLC- Site Number : 128
    • DuBois, Pennsylvania, United States, 15801-2277
      • Clinical Research Associates Of Central Pa , Llc
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Health Milton S. Hershey Medical Center
    • Hershey, Pennsylvania, United States, 17033-2360
      • Penn State Health Milton S. Hershey Medical Center- Site Number : 122
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital- Site Number : 130
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303-4225
      • Velocity Clinical Research - Spartanburg - PPDS- Site Number : 120
    • Spartanburg, South Carolina, United States, 29303
      • Velocity Clinical Research - Spartanburg - PPDS
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital- Site Number : 113
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah Health
    • Salt Lake City, Utah, United States, 84132-0001
      • University of Utah Health Care- Site Number : 106

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Zemaira (A1PI); 60 mg/kg IV once weekly (QW) and placebo (normal saline)	Drug: Zemaira; Alpha1-Proteinase Inhibitor (Human); Other Names: Respreeza
Experimental: SAR447537 (INBRX-101) Q3W; IV every 3-weeks (Q3W) and placebo (normal saline)	Drug: SAR447537; A1PI, Recombinant, Bivalent Fc Fusion Protein
Experimental: SAR447537 (INBRX-101) Q4W; IV every 4-weeks (Q4W) and placebo (normal saline)	Drug: SAR447537; A1PI, Recombinant, Bivalent Fc Fusion Protein

What is the study measuring?

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 participants treated with SAR447537 compared to A1PI	32 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
fAAT Concentration changes	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.	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 participants treated with SAR447537 compared to A1PI.	32 weeks
Incidence of TEAEs	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).	32 Weeks
Anti-drug antibodies	Frequency of anti-drug antibodies (ADA) against SAR447537 and endogenous AAT, as well as neutralizing ADA (NAb) against SAR447537 and endogenous AAT.	32 Weeks
Population Pharmacokinetics: Clearance	Modeling by means of appropriate software to characterize the pharmacokinetic profile of SAR447537 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 SAR447537 via estimation of the parameter volume of distribution	32 Weeks
Covariate Analysis: Biometric Values: Weight	Assessment of the impact of participant's weight [in kg] on the pharmacokinetic profile of SAR447537	32 Weeks
Covariate Analysis: Biometric Values: Height	Assessment of the impact of participant's height [in cm] on the pharmacokinetic profile of SAR447537	32 Weeks
Covariate Analysis: Biometric Values: Age	Assessment of the impact of participant's age [in years] on the pharmacokinetic profile of SAR447537	32 Weeks
Covariate Analysis: Biometric Values: Sex	Assessment of the impact of participant's sex [male or female] on the pharmacokinetic profile of SAR447537	32 Weeks

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): October 12, 2023
• Primary Completion (Actual): August 6, 2025
• Study Completion (Actual): August 6, 2025

Study Registration Dates

• First Submitted: March 28, 2023
• First Submitted That Met QC Criteria: May 9, 2023
• First Posted (Actual): May 12, 2023

Study Record Updates

• Last Update Posted (Actual): August 11, 2025
• Last Update Submitted That Met QC Criteria: August 8, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Emphysema; AATD; Alpha 1-Antitrypsin Deficiency; AAT; INBRX-101; A1PI; SAR447537
• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Genetic Diseases, Inborn; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Lung Diseases, Obstructive; Liver Diseases; Subcutaneous Emphysema; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Emphysema; Alpha 1-Antitrypsin Deficiency; Molecular Mechanisms of Pharmacological Action; Protease Inhibitors; Enzyme Inhibitors; Serine Proteinase Inhibitors; Trypsin Inhibitors; Alpha 1-Antitrypsin
• Other Study ID Numbers: INBRX101-01-201; 2023-508084-76-00 (Registry Identifier: CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No