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

Emphysema Clinical Trial

— ELEVAATE  

Official title:

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 Alpha1-Proteinase Inhibitor (A1PI) Augmentation Therapy in Adults With Alpha-1 Antitrypsin Deficiency (AATD) Emphysema

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05856331
• Other study ID #: INBRX101-01-201
• Status: Recruiting
• Phase: Phase 2
• Start date: October 12, 2023
• Est. completion date: March 2025

Study information

• Verified date: April 2024
• Source: Inhibrx, Inc.
• Contact: Gabe Berman
• Phone: 858-500-7833
• Email: clinicaltrials[@]inhibrx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

This is 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 Alpha1-Proteinase Inhibitor (A1PI) Augmentation Therapy in Adults With Alpha-1 Antitrypsin Deficiency (AATD) Emphysema.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: March 2025
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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 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

Related Conditions & MeSH terms

• Alpha 1-Antitrypsin Deficiency
• Emphysema
• Pulmonary Emphysema

Intervention

Drug:
• INBRX-101
A1PI, Recombinant, Bivalent Fc Fusion Protein
• Zemaira
Alpha1-Proteinase Inhibitor (Human)

Locations

Country	Name	City	State
Australia	Eastern Health Clinical School	Box Hill	Victoria
Australia	Donna McIntyre	Brisbane	Queensland
Australia	Queensland Centre for Pulmonary Transplantation	Chermside	Queensland
Australia	St Vincent Hospital Melbourne	Fitzroy	Victoria
Australia	Frankston Hospital	Frankston	Victoria
Australia	Institute for Respiratory Health	Nedlands	Western Australia
Australia	Royal Adelaide Hospital	North Adelaide	South Australia
New Zealand	NZRSI	Greenlane	Auckland
New Zealand	P3 Research	Wellington
United Kingdom	Queen Elizabeth Hospital Birmingham	Birmingham	Warwickshire
United Kingdom	Ninewells Hospital - PPDS	Dundee	Angus
United Kingdom	Royal Devon and Exeter Hospital (Wonford) - Barrack Rd	Exeter	Devon
United Kingdom	Medicines Evaluation Unit	Manchester	Cheshire
United Kingdom	Southampton General Hospital	Southampton	Hampshire
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	University of Chicago	Chicago	Illinois
United States	Western Connecticut Medical Group	Danbury	Connecticut
United States	National Jewish Medical and Research Center	Denver	Colorado
United States	Clinical Research Associates Of Central PA , LLC	DuBois	Pennsylvania
United States	University of Florida	Gainesville	Florida
United States	Hannibal Clinic	Hannibal	Missouri
United States	Penn State Health Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Houston Methodist Hospital	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	David Geffen School of Medicine	Los Angeles	California
United States	Loyola University Medical Center	Maywood	Illinois
United States	University of Miami	Miami	Florida
United States	M Health Fairview Clinics and Surgery Center - Minneapolis	Minneapolis	Minnesota
United States	Columbia University	New York	New York
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	St Joseph's Hospital and Medical Center	Phoenix	Arizona
United States	Oregon Health and Science University	Portland	Oregon
United States	UC Davis Medical Center	Sacramento	California
United States	University of Utah Health	Salt Lake City	Utah
United States	Velocity Clinical Research - Spartanburg - PPDS	Spartanburg	South Carolina
United States	Pulmonary and Sleep of Tampa Bay	Tampa	Florida
United States	Cleveland Clinic Florida	Weston	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Inhibrx, Inc.

Countries where clinical trial is conducted

United States,  Australia,  New Zealand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 patients treated with INBRX-101 compared to A1PI	32 Weeks
Secondary	fAAT Concentration changes	Mean change in fAAT concentration from baseline to fAAT average concentration at steady-state (Cavg, ss) in patients treated with INBRX-101 compared to A1PI.	32 Weeks
Secondary	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 patients treated with INBRX-101 compared to A1PI.	32 weeks
Secondary	Incidence of TEAEs	Incidence of all treatment-emergent adverse events (TEAEs), TEAEs = Grade 3, serious adverse events (SAEs), TEAEs requiring withdrawal from IP treatment, and infusion reactions will be determined.	32 Weeks
Secondary	Anti-drug antibodies	Frequency of anti-drug antibodies (ADA) against INBRX-101 and endogenous AAT, as well as neutralizing ADA (NAb) against INBRX-101 and endogenous AAT will be determined.	32 Weeks
Secondary	Population Pharmacokinetics: Clearance	Modeling by means of appropriate software to characterize the pharmacokinetic profile of INBRX-101 via estimation of the parameter clearance	32 Weeks
Secondary	Population Pharmacokinetics: Volume of Distribution	Modeling by means of appropriate software to characterize the pharmacokinetic profile of INBRX-101 via estimation of the parameter volume of distribution	32 Weeks
Secondary	Covariate Analysis: Biometric Values: Weight	Assessment of the impact of patient's weight [in kg] on the pharmacokinetic profile of INBRX-101	32 Weeks
Secondary	Covariate Analysis: Biometric Values: Height	Assessment of the impact of patient's height [in cm] on the pharmacokinetic profile of INBRX-101	32 Weeks
Secondary	Covariate Analysis: Biometric Values: Age	Assessment of the impact of patient's age [in years] on the pharmacokinetic profile of INBRX-101	32 Weeks
Secondary	Covariate Analysis: Biometric Values: Sex	Assessment of the impact of patient's sex [male or female] on the pharmacokinetic profile of INBRX-101	32 Weeks