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

• ClinicalTrials.gov Identifier: NCT03815396
• Recruitment Status: Completed
• First Posted: January 24, 2019
• Last Update Posted: September 13, 2022
• Sponsor: Inhibrx, Inc.
• Information provided by (Responsible Party): Inhibrx, Inc.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Alpha-1 Antitrypsin Deficiency; AATD	Drug: INBRX-101/rhAAT-Fc	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 31 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: July 19, 2019
• Actual Primary Completion Date: August 18, 2022
• Actual Study Completion Date: August 18, 2022

Arms and Interventions

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).

Outcome Measures

Primary Outcome Measures :

1. Frequency of adverse events of INBRX-101 [ Time Frame: Up to 7 months ]
   Adverse events will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03.
2. Severity of adverse events of INBRX-101 [ Time Frame: Up to 7 months ]
   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.

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, California

UC Davis School of Medicine

Sacramento, California, United States, 95817

United States, Florida

University of Florida College of Medicine

Gainesville, Florida, United States, 32611

University of Miami

Miami, Florida, United States, 33125

United States, Indiana

Indiana University

Indianapolis, Indiana, United States, 46202

United States, Missouri

Hannibal Clinic

Hannibal, Missouri, United States, 63401

New Zealand

The New Zealand Respiratory and Sleep Institute

Auckland, New Zealand

Christchurch Clinical Studies Trust Ltd

Christchurch, New Zealand

Waikato Respiratory and Gastro Research Unit

Hamilton, New Zealand

United Kingdom

University of Cambridge

Cambridge, East Of England, United Kingdom, CB2 0QQ

University Hospital Birmingham NHS Foundation Trust

Birmingham, West Midlands, United Kingdom, B15 2GW

Sponsors and Collaborators

Inhibrx, Inc.

Investigators

• Study Director: Vasily Andrianov, MD; Inhibrx, Inc.

More Information

• Responsible Party: Inhibrx, Inc.
• ClinicalTrials.gov Identifier: NCT03815396
• Other Study ID Numbers: Ph1 INBRX-101
• First Posted: January 24, 2019
• Last Update Posted: September 13, 2022
• Last Verified: September 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Inhibrx, Inc.:

Alpha-1 antitrypsin deficiency; AATD; alpha-1 disease; AAT

Additional relevant MeSH terms:

Alpha 1-Antitrypsin Deficiency; Liver Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Subcutaneous Emphysema; Emphysema; Pathologic Processes