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 Alpha-1 Proteinase Inhibitor (A1PI) Augmentation Therapy in Adults with Alpha-1 Antitrypsin Deficiency (AATD) Emphysema.
Cynthia Brown, MD
Primary Investigator
Brief description of study
Detailed description of study
What will happen during the study?
Prior to randomization into the double-blind, treatment phase, patients will provide informed
consent, undergo screening for up to 7 weeks (49-days) to determine study eligibility, and
complete the 5-week (35-days) washout required for patients receiving A1PI augmentation
therapy. Antigenic AAT levels, confirmed by the central laboratory, will be obtained during
screening (after completion of the required A1PI washout) as part of the eligibility
assessment.
After eligibility has been confirmed, patients will be randomized 2:2:1 to receive one of the
following dose regimens:
• INBRX-101 (N=36) at 120 mg/kg, intravenous (IV) every 3-weeks (Q3W) and
placebo (site supplied normal saline) IV on non-dosing weeks
• INBRX-101 (N=36) at 120 mg/kg IV every 4-weeks (Q4W) and placebo (site
supplied normal saline) IV on non-dosing weeks
• A1PI (N=18) at the approved dose of 60 mg/kg IV once weekly (QW).
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: Alpha-1 Antitrypsin Deficiency (AATD), Emphysema
-
Age: 18 years - 80 years
-
Gender: All
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 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
