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

NCT03815396 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: Ph1 INBRX-101
• Study Type: interventional
• Target: 31
• Locations: 3 countries
• Sites: 10

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.

Conditions

Alpha-1 Antitrypsin Deficiency; AATD

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (8)

• Area under the serum concentration time curve (AUC) of INBRX-101

  Up to 7 months

• Maximum observed serum concentration (Cmax) of INBRX-101

  Up to 7 months

• Trough observed serum concentration (Ctrough) of INBRX-101

  Up to 7 months

• Time to Cmax (Tmax) of INBRX-101

  Up to 7 months

• Half-life (T1/2) of INBRX-101

  Up to 7 months

Study Arms (2)

Part 1 Single Ascending Dose

EXPERIMENTAL

INBRX-101 will be escalated in subjects with alpha-1 antitrypsin deficiency (AATD).

Drug: INBRX-101/rhAAT-Fc

Part 2 Multiple Ascending Dose

EXPERIMENTAL

INBRX-101 will be escalated in subjects with alpha-1 antitrypsin deficiency (AATD).

Drug: INBRX-101/rhAAT-Fc

Interventions

INBRX-101/rhAAT-Fc DRUG

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

Part 1 Single Ascending Dose; Part 2 Multiple Ascending Dose

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Inhibrx Biosciences, Inc: lead

Study Sites (10)

UC Davis School of Medicine

Sacramento, California, 95817, United States

Location

University of Florida College of Medicine

Gainesville, Florida, 32611, United States

Location

University of Miami

Miami, Florida, 33125, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Hannibal Clinic

Hannibal, Missouri, 63401, United States

Location

The New Zealand Respiratory and Sleep Institute

Auckland, New Zealand

Location

Christchurch Clinical Studies Trust Ltd

Christchurch, New Zealand

Location

Waikato Respiratory and Gastro Research Unit

Hamilton, New Zealand

Location

University of Cambridge

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

Location

University Hospital Birmingham NHS Foundation Trust

Birmingham, West Midlands, B15 2GW, United Kingdom

Location

MeSH Terms

Conditions

alpha 1-Antitrypsin Deficiency

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Subcutaneous Emphysema; Emphysema; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Vasily Andrianov, MD

  Inhibrx Biosciences, Inc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2019
• First Posted: January 24, 2019
• Study Start: July 19, 2019
• Primary Completion: August 18, 2022
• Study Completion: August 18, 2022
• Last Updated: September 13, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2); US (5); NZ (3)