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

Primary Purpose

Alpha-1 Antitrypsin Deficiency, AATD

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
INBRX-101/rhAAT-Fc
Sponsored by
Inhibrx, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alpha-1 Antitrypsin Deficiency focused on measuring Alpha-1 antitrypsin deficiency, AATD, alpha-1 disease, AAT

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • UC Davis School of Medicine
  • University of Florida College of Medicine
  • University of Miami
  • Indiana University
  • Hannibal Clinic
  • The New Zealand Respiratory and Sleep Institute
  • Christchurch Clinical Studies Trust Ltd
  • Waikato Respiratory and Gastro Research Unit
  • University of Cambridge
  • University Hospital Birmingham NHS Foundation Trust

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Part 1 Single Ascending Dose

Part 2 Multiple Ascending Dose

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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

Full Information

First Posted
January 21, 2019
Last Updated
September 9, 2022
Sponsor
Inhibrx, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03815396
Brief Title
Phase 1 Study to Assess the Safety, PK and PD of INBRX-101 in Adults With Alpha-1 Antitrypsin Deficiency
Acronym
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)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Completed
Study Start Date
July 19, 2019 (Actual)
Primary Completion Date
August 18, 2022 (Actual)
Study Completion Date
August 18, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Inhibrx, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alpha-1 Antitrypsin Deficiency, AATD
Keywords
Alpha-1 antitrypsin deficiency, AATD, alpha-1 disease, AAT

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
31 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part 1 Single Ascending Dose
Arm Type
Experimental
Arm Description
INBRX-101 will be escalated in subjects with alpha-1 antitrypsin deficiency (AATD).
Arm Title
Part 2 Multiple Ascending Dose
Arm Type
Experimental
Arm Description
INBRX-101 will be escalated in subjects with alpha-1 antitrypsin deficiency (AATD).
Intervention Type
Drug
Intervention Name(s)
INBRX-101/rhAAT-Fc
Intervention Description
INBRX-101 is a recombinant human alpha-1 antitrypsin (AAT) Fc fusion protein (rhAAT-Fc).
Primary Outcome Measure Information:
Title
Frequency of adverse events of INBRX-101
Description
Adverse events will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03.
Time Frame
Up to 7 months
Title
Severity of adverse events of INBRX-101
Description
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.
Time Frame
Up to 7 months
Secondary Outcome Measure Information:
Title
Area under the serum concentration time curve (AUC) of INBRX-101
Description
Area under the serum concentration time curve (AUC) of INBRX-101 will be determined.
Time Frame
Up to 7 months
Title
Maximum observed serum concentration (Cmax) of INBRX-101
Description
Maximum observed serum concentration (Cmax) of INBRX-101 will be determined.
Time Frame
Up to 7 months
Title
Trough observed serum concentration (Ctrough) of INBRX-101
Description
Trough observed serum concentration (Cmax) of INBRX-101 will be determined.
Time Frame
Up to 7 months
Title
Time to Cmax (Tmax) of INBRX-101
Description
Time to Cmax (Tmax) of INBRX-101 will be determined.
Time Frame
Up to 7 months
Title
Half-life (T1/2) of INBRX-101
Description
Half-life of INBRX-101 will be determined.
Time Frame
Up to 7 months
Title
Immunogenicity of INBRX-101
Description
Frequency and consequences of anti-drug antibodies (ADA) against INBRX-101 will be determined.
Time Frame
Up to 7 months
Title
Distribution of INBRX-101 in Bronchoalveolar Lavage Fluid (BALF)
Description
The concentration of INBRX-101 in bronchoalveolar lavage fluid (BALF) be determined.
Time Frame
Up to 7 months
Title
Functional concentration of INBRX-101 in serum and BALF
Description
The functional concentration of INBRX-101 in serum and BALF will be determined.
Time Frame
Up to 7 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vasily Andrianov, MD
Organizational Affiliation
Inhibrx, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
UC Davis School of Medicine
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
University of Florida College of Medicine
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32611
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33125
Country
United States
Facility Name
Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Hannibal Clinic
City
Hannibal
State/Province
Missouri
ZIP/Postal Code
63401
Country
United States
Facility Name
The New Zealand Respiratory and Sleep Institute
City
Auckland
Country
New Zealand
Facility Name
Christchurch Clinical Studies Trust Ltd
City
Christchurch
Country
New Zealand
Facility Name
Waikato Respiratory and Gastro Research Unit
City
Hamilton
Country
New Zealand
Facility Name
University of Cambridge
City
Cambridge
State/Province
East Of England
ZIP/Postal Code
CB2 0QQ
Country
United Kingdom
Facility Name
University Hospital Birmingham NHS Foundation Trust
City
Birmingham
State/Province
West Midlands
ZIP/Postal Code
B15 2GW
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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