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

Phase 1

Completed

• Conditions: Alpha-1 Antitrypsin Deficiency; AATD
• Interventions: Drug: INBRX-101/rhAAT-Fc

• Registration Number: NCT03815396
• Lead Sponsor: Inhibrx Biosciences, Inc

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-01-21
• Study First Submitted QC: 2019-01-21
• Study First Posted: 2019-01-24
• Study Start: 2019-07-19
• Primary Completion: 2022-08-18
• Study Completion: 2022-08-18
• Status Verified: 2022-09
• Last Update Submitted: 2022-09-09
• Last Update Posted: 2022-09-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 31

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part 1 Single Ascending Dose	INBRX-101/rhAAT-Fc	INBRX-101 will be escalated in subjects with alpha-1 antitrypsin deficiency (AATD).
Part 2 Multiple Ascending Dose	INBRX-101/rhAAT-Fc	INBRX-101 will be escalated in subjects with alpha-1 antitrypsin deficiency (AATD).

Primary Outcome Measures

Name	Time	Method
Frequency of adverse events of INBRX-101	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.
Severity of adverse events of INBRX-101	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

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

Trial Locations

Locations (10)

UC Davis School of Medicine; 🇺🇸 Sacramento, California, United States

Indiana University; 🇺🇸 Indianapolis, Indiana, United States

University of Miami; 🇺🇸 Miami, Florida, United States

University of Florida College of Medicine; 🇺🇸 Gainesville, Florida, United States

The New Zealand Respiratory and Sleep Institute; 🇳🇿 Auckland, New Zealand

Waikato Respiratory and Gastro Research Unit; 🇳🇿 Hamilton, New Zealand

Hannibal Clinic; 🇺🇸 Hannibal, Missouri, United States

Christchurch Clinical Studies Trust Ltd; 🇳🇿 Christchurch, New Zealand

University of Cambridge; 🇬🇧 Cambridge, East Of England, United Kingdom

University Hospital Birmingham NHS Foundation Trust; 🇬🇧 Birmingham, West Midlands, United Kingdom