Long-term, Open-label Study of SAR447537 (INBRX-101) in Adults With Alpha-1 Antitrypsin Deficiency Emphysema (ELEVAATE OLE)

A Phase 2, Single Arm, Open Label Extension Study, Evaluating the Long-Term Safety and Clinical Efficacy of SAR447537 (INBRX-101) in Adults With Alpha-1 Antitrypsin Deficiency (AATD) Emphysema

Phase 2 open label extension study to evaluate SAR447537 (INBRX-101) in adults with AATD emphysema

Study Overview

• Status: Active, not recruiting
• Conditions: Emphysema; Alpha 1-Antitrypsin Deficiency
• Intervention / Treatment: Drug: SAR447537

Detailed Description

This is a Phase 2, Single Arm, Open Label Extension Study, Evaluating the Long-Term Safety and Clinical Efficacy of SAR447537 (INBRX-101) in Adults With Alpha-1 Antitrypsin Deficiency (AATD) Emphysema.

• Study Type: Interventional
• Enrollment (Estimated): 185
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Chermside, Queensland, Australia, 4032
      • Investigational Site Number : 202
    • South Brisbane, Queensland, Australia, 4101
      • Investigational Site Number : 204
  • South Australia
    • North Adelaide, South Australia, Australia, 5000
      • Investigational Site Number : 201
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Investigational Site Number : 207
    • Fitzroy, Victoria, Australia, 3065
      • Investigational Site Number : 203
    • Frankston, Victoria, Australia, 3199
      • Investigational Site Number : 205
• Denmark
  • Hellerup, Denmark, 2900
    • Investigational Site Number : 701
  • Vejle, Denmark, 7100
    • Investigational Site Number : 702
• Ireland
  • Dublin
    • Dublin, Dublin, Ireland, D09 XR63
      • Investigational Site Number : 501
• New Zealand
  • Auckland, New Zealand, 1051
    • Investigational Site Number : 403
  • Wellington, New Zealand, 6021
    • Investigational Site Number : 404
• Poland
  • Krakow, Poland, 30-688
    • Investigational Site Number : 802
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 01-138
      • Investigational Site Number : 801
• Spain
  • Madrid, Spain, 28040
    • Investigational Site Number : 902
  • Santiago de Compostela, Spain, 15706
    • Investigational Site Number : 903
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Investigational Site Number : 901
• Sweden
  • Gothenburg, Sweden, 413 46
    • Investigational Site Number : 601
• United Kingdom
  • Coventry, United Kingdom, CV2 2DX
    • Investigational Site Number : 309
  • Angus
    • Dundee, Angus, United Kingdom, DD1 9SY
      • Investigational Site Number : 308
  • Cheshire
    • Wythenshawe, Cheshire, United Kingdom, M23 9QZ
      • Investigational Site Number : 306
  • Devon
    • Exeter, Devon, United Kingdom, EX2 5DW
      • Investigational Site Number : 307
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
      • Investigational Site Number : 304
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205-2610
      • UAB Lung Health Center- Site Number : 105
  • Arizona
    • Phoenix, Arizona, United States, 85013-4220
      • St Joseph's Hospital and Medical Center- Site Number : 126
  • California
    • Los Angeles, California, United States, 90095-3075
      • David Geffen School of Medicine at UCLA- Site Number : 124
    • Sacramento, California, United States, 95817-2201
      • University of California Davis Medical Center- Site Number : 110
  • Colorado
    • Denver, Colorado, United States, 80206-2761
      • National Jewish Medical and Research Center- Site Number : 123
  • Connecticut
    • Danbury, Connecticut, United States, 06810-5038
      • Nuvance Health Medical Practices, Pulmonary & Sleep Specialists- Site Number : 119
  • Florida
    • Gainesville, Florida, United States, 32610-3003
      • University of Florida - Gainesville - 1600 SW Archer Rd- Site Number : 101
  • Indiana
    • Indianapolis, Indiana, United States, 46202-5128
      • Indiana University- Site Number : 127
  • Massachusetts
    • Boston, Massachusetts, United States, 02115-6105
      • Brigham and Women's Hospital -75 Francis Street- Site Number : 131
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455-0341
      • University of Minnesota-420 Delaware Str SE- Site Number : 125
  • Missouri
    • Hannibal, Missouri, United States, 63401-6890
      • Hannibal Regional Healthcare System-HRMG-Hannibal- Site Number : 111
  • New York
    • New York, New York, United States, 10032-3729
      • Columbia University Irving Medical Center- Site Number : 104
  • Oregon
    • Portland, Oregon, United States, 97239-3011
      • Oregon Health and Science University- Site Number : 117
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033-2360
      • Penn State Health Milton S. Hershey Medical Center- Site Number : 122
    • Philadelphia, Pennsylvania, United States, 19140-5103
      • Temple University Hospital - 3401 N Broad St- Site Number : 130
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303-4225
      • Velocity Clinical Research - Spartanburg - PPDS- Site Number : 120
  • Texas
    • Houston, Texas, United States, 77030-2703
      • Houston Methodist Hospital- Site Number : 113
  • Utah
    • 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% predicted at screening and post-bronchodilator FEV1/FVC<0.7
5. Current non-smoking status

Exclusion Criteria:

For newly identified participants

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, A1PI or human IgG
3. Uncontrolled diabetes mellitus despite adequate antidiabetic pharmacologic treatment with a screening HbA1c value ≥9%
4. Received IV immunoglobulins, monoclonal antibodies and/or other biologic therapies within 30 days
5. On waiting list for lung or liver transplant
6. Acute respiratory tract infection or COPD exacerbation within 4 weeks prior to or during screening
7. Evidence of decompensated cirrhosis
8. Active cancers or has a history of malignancy within 5 years prior to screening
9. History of unstable cor pulmonale

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SAR447537 (INBRX-101); A1PI, Recombinant, Bivalent Fc Fusion Protein, in a solution for intravenous injection	Drug: SAR447537; A1PI, Recombinant, Bivalent Fc Fusion Protein

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long-term safety and tolerability	Incidence of all treatment emergent adverse events (TEAEs), TEAEs ≥ Grade 3, serious adverse events (SAEs), TEAEs leading to discontinuation from SAR447537, and adverse events of special interest (AESIs) (including infusion-related reactions).	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trough serum functional AAT (fAAT) concentration changes	Change in fAAT concentration levels from baseline to end of treatment	3 years
Change in lung density by quantitative computerized tomography (CT)	Assess the annual rate of change in lung density assessed by serial quantitative CT (15th percentile point, PD15) at total lung capacity (TLC), centrally read, from baseline to end of treatment (EoT).	3 years
Trough SAR447537 concentration changes	Change in SAR447537 concentration levels from baseline to end of treatment	3 years
Covariate Analysis: Biometric Values: Weight	Assessment of the impact of participant's weight [in kg] on the pharmacokinetic profile of SAR447537	3 years
Covariate Analysis: Biometric Values: Height	Assessment of the impact of participant's height [in cm] on the pharmacokinetic profile of SAR447537	3 years
Covariate Analysis: Biometric Values: Age	Assessment of the impact of participant's age [in years] on the pharmacokinetic profile of SAR447537	3 years
Covariate Analysis: Biometric Values: Sex	Assessment of the impact of participant's sex [male or female] on the pharmacokinetic profile of SAR447537	3 years
Anti-drug antibodies	Frequency of anti-drug antibodies (ADA) against SAR447537 as well as neutralizing ADA (NAb) against SAR447537	3 years

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• INBRX101-01-202 Plain Language Results Summary

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2024
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): September 30, 2028

Study Registration Dates

• First Submitted: May 31, 2023
• First Submitted That Met QC Criteria: May 31, 2023
• First Posted (Actual): June 9, 2023

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 8, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Emphysema; AATD; Alpha 1-Antitrypsin Deficiency; AAT; INBRX-101; SAR447537
• Additional Relevant MeSH Terms: Pathologic Processes; Genetic Diseases, Inborn; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Liver Diseases; Subcutaneous Emphysema; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Emphysema; alpha 1-Antitrypsin Deficiency
• Other Study ID Numbers: INBRX101-01-202; 2023-508137-14-00 (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