Phase 1 Study to Assess the Safety, PK and PD of INBRX-101 in Adults With Alpha-1 Antitrypsin Deficiency (rhAAT-Fc)

An Open-Label, Multicenter, Phase 1 Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Intravenous Doses of Inhibrx rhAAT-Fc (INBRX-101) in Adults With Alpha-1 Antitrypsin Deficiency (AATD)

This is an open-label, 2-part, dose-escalating, Phase 1 study of INBRX-101 (rhAAT-Fc). Part 1 will consist of single ascending dose (SAD) administration of INBRX-101 and Part 2 will consist of multiple ascending dose (MAD) administrations of INBRX-101. The planned dosing schedule is IV every 3 to 4 weeks.

Study Overview

• Status: Completed
• Conditions: Alpha-1 Antitrypsin Deficiency; AATD
• Intervention / Treatment: Drug: INBRX-101/rhAAT-Fc

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

• New Zealand
  • Auckland, New Zealand
    • The New Zealand Respiratory and Sleep Institute
  • Christchurch, New Zealand
    • Christchurch Clinical Studies Trust Ltd
  • Hamilton, New Zealand
    • Waikato Respiratory and Gastro Research Unit
• United Kingdom
  • East Of England
    • Cambridge, East Of England, United Kingdom, CB2 0QQ
      • University of Cambridge
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B15 2GW
      • University Hospital Birmingham NHS Foundation Trust
• United States
  • California
    • Sacramento, California, United States, 95817
      • UC Davis School of Medicine
  • Florida
    • Gainesville, Florida, United States, 32611
      • University of Florida College of Medicine
    • Miami, Florida, United States, 33125
      • University of Miami
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Missouri
    • Hannibal, Missouri, United States, 63401
      • Hannibal Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Documented alpha-1 antitrypsin (AAT) serum concentration <11 μM.
• Diagnosis of alpha-1 antitrypsin deficiency (AATD) with any allelic combination with exception of the null/null genotype.
• For subjects in Part 2 80 and 120 mg/kg cohorts ONLY: post-bronchodilator FEV1 of at least 40% of predicted normal value.
• For subjects in Part 2 80 and 120 mg/kg cohorts ONLY: subjects eligible for bronchoscopy per judgment of investigator.
• Nonsmoker for at least 6 months prior to study and must remain nonsmoking for the entire study duration.
• Adequate hepatic and renal function as defined per protocol.
• Willing to undergo current augmentation therapy washout (if applicable) and refrain from initiating augmentation therapy, other investigational drug trials for AATD, therapy with IV immunoglobulins or monoclonal antibodies during the entire study, including follow-up.

Exclusion Criteria:

• Known or suspected allergy to components of INBRX-101 (AAT or human IgG) or pdAAT.
• Participation in any investigational drug trial within 30 days prior to this trial, or subjects receiving IV immunoglobulins or monoclonal antibodies within 30 days prior to this trial.
• History of and/or on the waiting list for lung or liver transplant, lobectomy, or lung volume reduction surgery.
• Acute respiratory tract infection or COPD exacerbation that required antibiotic treatment and/or increase in systemic steroid dosage within the 4 weeks prior to screening. Subjects are permitted to continue to receive steroids if the investigator judges the subject to have a history of stable dosing.
• Subjects with ongoing or history of unstable cor pulmonale.
• Infection with hepatitis A, B, or C or human immunodeficiency virus (HIV).
• Active autoimmune disease or documented history of autoimmune disease that 1) required systemic steroids or immune-suppressive medications and 2) tested positive for auto-antibodies. Exception: Endocrinopathies managed with hormone replacement therapy (HRT).
• Current substance and/or alcohol abuse with protocol defined exceptions.
• Current narcotics abuse with protocol defined exceptions.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 Single Ascending Dose; INBRX-101 will be escalated in subjects with alpha-1 antitrypsin deficiency (AATD).	Drug: INBRX-101/rhAAT-Fc; INBRX-101 is a recombinant human alpha-1 antitrypsin (AAT) Fc fusion protein (rhAAT-Fc).
Experimental: Part 2 Multiple Ascending Dose; INBRX-101 will be escalated in subjects with alpha-1 antitrypsin deficiency (AATD).	Drug: INBRX-101/rhAAT-Fc; INBRX-101 is a recombinant human alpha-1 antitrypsin (AAT) Fc fusion protein (rhAAT-Fc).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of adverse events of INBRX-101	Adverse events will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03.	Up to 7 months
Severity of adverse events of INBRX-101	Severity of adverse events will be assessed and assigned by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03.	Up to 7 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the serum concentration time curve (AUC) of INBRX-101	Area under the serum concentration time curve (AUC) of INBRX-101 will be determined.	Up to 7 months
Maximum observed serum concentration (Cmax) of INBRX-101	Maximum observed serum concentration (Cmax) of INBRX-101 will be determined.	Up to 7 months
Trough observed serum concentration (Ctrough) of INBRX-101	Trough observed serum concentration (Cmax) of INBRX-101 will be determined.	Up to 7 months
Time to Cmax (Tmax) of INBRX-101	Time to Cmax (Tmax) of INBRX-101 will be determined.	Up to 7 months
Half-life (T1/2) of INBRX-101	Half-life of INBRX-101 will be determined.	Up to 7 months
Immunogenicity of INBRX-101	Frequency and consequences of anti-drug antibodies (ADA) against INBRX-101 will be determined.	Up to 7 months
Distribution of INBRX-101 in Bronchoalveolar Lavage Fluid (BALF)	The concentration of INBRX-101 in bronchoalveolar lavage fluid (BALF) be determined.	Up to 7 months
Functional concentration of INBRX-101 in serum and BALF	The functional concentration of INBRX-101 in serum and BALF will be determined.	Up to 7 months

Collaborators and Investigators

• Sponsor: Inhibrx, Inc.
• Investigators: Study Director: Vasily Andrianov, MD, Inhibrx, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2019
• Primary Completion (Actual): August 18, 2022
• Study Completion (Actual): August 18, 2022

Study Registration Dates

• First Submitted: January 21, 2019
• First Submitted That Met QC Criteria: January 21, 2019
• First Posted (Actual): January 24, 2019

Study Record Updates

• Last Update Posted (Actual): September 13, 2022
• Last Update Submitted That Met QC Criteria: September 9, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Alpha-1 antitrypsin deficiency; AATD; AAT; alpha-1 disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Liver Diseases; Genetic Diseases, Inborn; Subcutaneous Emphysema; Emphysema; Alpha 1-Antitrypsin Deficiency
• Other Study ID Numbers: Ph1 INBRX-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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