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

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Brief Title

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

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)

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.
    


Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

Frequency of adverse events of INBRX-101

Secondary Outcome

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

Condition

Alpha-1 Antitrypsin Deficiency

Intervention

INBRX-101/rhAAT-Fc

Study Arms / Comparison Groups

 Part 1 Single Ascending Dose
Description:  INBRX-101 will be escalated in subjects with alpha-1 antitrypsin deficiency (AATD).

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

30

Start Date

July 19, 2019

Completion Date

December 2021

Primary Completion Date

December 2021

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.
      

Gender

All

Ages

18 Years - 80 Years

Accepts Healthy Volunteers

No

Contacts

Klaus Wagner, MD, PhD, , 

Location Countries

United Kingdom

Location Countries

United Kingdom

Administrative Informations


NCT ID

NCT03815396

Organization ID

Ph1 INBRX-101


Responsible Party

Sponsor

Study Sponsor

Inhibrx, Inc.


Study Sponsor

Klaus Wagner, MD, PhD, Study Director, CMO


Verification Date

May 2020