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

Alpha-1 Antitrypsin Deficiency Clinical Trial

— rhAAT-Fc  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03815396
• Other study ID #: Ph1 INBRX-101
• Status: Completed
• Phase: Phase 1
• Start date: July 19, 2019
• Est. completion date: August 18, 2022

Study information

• Verified date: September 2022
• Source: Inhibrx, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: August 18, 2022
• Est. primary completion date: August 18, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• AATD
• Alpha 1-Antitrypsin Deficiency
• Alpha-1 Antitrypsin Deficiency

Intervention

Drug:
• INBRX-101/rhAAT-Fc
INBRX-101 is a recombinant human alpha-1 antitrypsin (AAT) Fc fusion protein (rhAAT-Fc).

Locations

Country	Name	City	State
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
United Kingdom	University Hospital Birmingham NHS Foundation Trust	Birmingham	West Midlands
United Kingdom	University of Cambridge	Cambridge	East Of England
United States	University of Florida College of Medicine	Gainesville	Florida
United States	Hannibal Clinic	Hannibal	Missouri
United States	Indiana University	Indianapolis	Indiana
United States	University of Miami	Miami	Florida
United States	UC Davis School of Medicine	Sacramento	California

Sponsors (1)

Lead Sponsor	Collaborator
Inhibrx, Inc.

Countries where clinical trial is conducted

United States,  New Zealand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	Maximum observed serum concentration (Cmax) of INBRX-101	Maximum observed serum concentration (Cmax) of INBRX-101 will be determined.	Up to 7 months
Secondary	Trough observed serum concentration (Ctrough) of INBRX-101	Trough observed serum concentration (Cmax) of INBRX-101 will be determined.	Up to 7 months
Secondary	Time to Cmax (Tmax) of INBRX-101	Time to Cmax (Tmax) of INBRX-101 will be determined.	Up to 7 months
Secondary	Half-life (T1/2) of INBRX-101	Half-life of INBRX-101 will be determined.	Up to 7 months
Secondary	Immunogenicity of INBRX-101	Frequency and consequences of anti-drug antibodies (ADA) against INBRX-101 will be determined.	Up to 7 months
Secondary	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
Secondary	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