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Trial record 1 of 1 for:    NCT03946449
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Study of ARO-AAT in Patients With Alpha-1 Antitrypsin Deficiency Associated Liver Disease (AATD)

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ClinicalTrials.gov Identifier: NCT03946449
Recruitment Status : Active, not recruiting
First Posted : May 10, 2019
Last Update Posted : April 1, 2021
Sponsor:
Information provided by (Responsible Party):
Arrowhead Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE May 8, 2019
First Posted Date  ICMJE May 10, 2019
Last Update Posted Date April 1, 2021
Actual Study Start Date  ICMJE December 19, 2019
Estimated Primary Completion Date August 23, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 29, 2021)
Change From Baseline Over Time in Total, Soluble, and Insoluble Z-Alpha 1 Antitrypsin (Z-AAT) Liver Concentrations [ Time Frame: Baseline and Week 24 (Cohort 1 &1b) or Week 48 (Cohort 2); Extension Cohort: Extension Week 44 ]
Original Primary Outcome Measures  ICMJE
 (submitted: May 9, 2019)
Change From Baseline Over Time in a Histological Liver Disease Activity Scale [ Time Frame: Baseline and Week 24 (Cohort 1) or Week 48 (Cohort 2); Extension Cohort: Baseline and Extension Week 44 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 29, 2021)
  • Change From Baseline Over Time in Circulating Levels of Z-AAT [ Time Frame: Baseline through Week 24 (Cohort 1 & 1b) or through Week 48 (Cohort 2); Extension Cohort: Baseline through Extension Weeks 44 and 92 ]
  • Change From Baseline Over Time in Alanine Transaminase (ALT) [ Time Frame: Baseline through Week 24 (Cohort 1 & 1b) or Week 48 (Cohort 2); Extension Cohort: Baseline through Extension Weeks 44 and 92 ]
  • Change From Baseline Over Time in Gamma-Glutamyl Transferase (GGT) [ Time Frame: Baseline and Week 24 (Cohort 1 & 1b) or Week 48 (Cohort 2); Extension Cohort: Baseline and Extension Weeks 44 and 92 ]
  • Change From Baseline Over Time in Fibrosis-4 Index (FIB4) [ Time Frame: Baseline through Week 24 (Cohort 1 & 1b) or Week 48 (Cohort 2); Extension Cohort: Baseline through Extension Weeks 44 and 92 ]
  • Change From Baseline Over Time in Aspartate Transaminase (AST) to Platelet Ratio Index (APRI) [ Time Frame: Baseline through Week 24 (Cohort 1 & 1b) or Week 48 (Cohort 2); Extension Cohort: Baseline through Extension Weeks 44 and 92 ]
  • Change From Baseline Over Time in Plasma Collagen Type 3 (PRO-C3) [ Time Frame: Baseline through Week 24 (Cohort 1 & 1b) or Week 48 (Cohort 2); Extension Cohort: Baseline through Extension Weeks 44 and 92 ]
  • Change From Baseline Over Time in Hepatic Stiffness based on FibroScan (when available) [ Time Frame: Baseline and Week 24 (Cohort 1 & 1b) or Week 48 (Cohort 2); Extension Cohort: Baseline and Extension Weeks 44 and 92 ]
  • Change From Baseline Over Time in Histological Metrics of Liver Disease: Inflammation Score [ Time Frame: Baseline and Week 24 (Cohort 1 &1b) or Week 48 (Cohort 2); Extension Cohort: Extension Week 44 ]
    Change in inflammation score, based on pathology slide reads. Inflammation was assessed on a scale of 0-3, with higher scores showing more severe inflammation.
  • Change From Baseline Over Time in Histological Metrics of Liver Disease: Steatosis Score [ Time Frame: Baseline and Week 24 (Cohort 1 &1b) or Week 48 (Cohort 2); Extension Cohort: Extension Week 44 ]
    Change in steatosis score, based on pathology slide reads. Steatosis was assessed on a scale of 0-3, with higher scores showing more severe steatosis.
  • Change From Baseline Over Time in Histological Metrics of Liver Disease: Hepatocyte Cell Death Score [ Time Frame: Baseline and Week 24 (Cohort 1 &1b) or Week 48 (Cohort 2); Extension Cohort: Extension Week 44 ]
    Change in hepatocyte cell death score, based on pathology slide reads. Hepatocyte cell death was assessed on a scale of 0-2, with higher scores showing more severe hepatocyte cell death.
  • Change From Baseline Over Time in Meta-analysis of Histological Data in Viral Hepatitis (METAVIR) Fibrosis Score [ Time Frame: Baseline and Week 24 (Cohort 1 & 1b) or Week 48 (Cohort 2); Extension Cohort: Extension Week 44 ]
    METAVIR scores range from F0 to F4 (F0=No Fibrosis, F1=Mild Fibrosis, F2= Significant Fibrosis, F3=Severe Fibrosis, F4=Cirrhosis). Higher scores indicate more severe fibrosis.
  • Number of Participants with Adverse Events (AEs) Possibly or Probably Related to Treatment [ Time Frame: Up to Week 24 (Cohort 1 & 1b) or Week 48 (Cohort 2); Extension Cohort: up to Extension Week 44 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 9, 2019)
  • Change From Baseline Over Time in Ishak Fibrosis Score [ Time Frame: Baseline and Week 24 (Cohort 1) or Week 48 (Cohort 2); Extension Cohort: Baseline and Extension Week 44 ]
  • Percentage Change From Baseline In Soluble Liver Z-Alpha-1 Antitrypsin (Z-AAT), Insoluble Liver Z-AAT Levels [ Time Frame: Baseline and Week 24 (Cohort 1) or Week 48 (Cohort 2); Extension Cohort: Baseline and Extension Week 44 ]
  • Percentage Change From Baseline in Serum AAT Levels [ Time Frame: Baseline and Week 24 (Cohort 1) or Week 48 (Cohort 2); Extension Cohort: Baseline and Extension Week 44 ]
  • Change From Baseline Over Time in Hepatic SERPINA1 mRNA Expression (if sufficient sample is available) [ Time Frame: Baseline and Week 24 (Cohort 1) or Week 48 (Cohort 2); Extension Cohort: Baseline and Extension Week 44 ]
  • Changes From Baseline Over Time in Liver Fibrosis Gene Expression (if scientifically feasible and sufficient sample is available) [ Time Frame: Baseline and Week 24 (Cohort 1) or Week 48 (Cohort 2); Extension Cohort: Baseline and Extension Week 44 ]
  • Number of Participants with Adverse Events (AEs) Possibly or Probably Related to Treatment [ Time Frame: Up to Week 24 (Cohort 1) or Week 48 (Cohort 2); Extension Cohort: up to Extension Week 44 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of ARO-AAT in Patients With Alpha-1 Antitrypsin Deficiency Associated Liver Disease (AATD)
Official Title  ICMJE A Pilot Open Label, Multi-dose, Phase 2 Study to Assess the Safety and Efficacy of ARO-AAT in Patients With Alpha-1 Antitrypsin Deficiency Associated Liver Disease (AATD)
Brief Summary The purpose of this study is to evaluate the the safety and efficacy of ARO-AAT Injection (also referred to as ARO-AAT) administered subcutaneously to patients with alpha-1 antitrypsin deficiency.
Detailed Description Participants will be enrolled to receive multiple subcutaneous injections of ARO-AAT. All eligible participants will require a pre-dose biopsy completed as part of the study within the screening window. All participants will undergo an End of Study (EOS) biopsy. Treated participants will be offered the opportunity to continue treatment in an open label extension during which they will undergo a final biopsy.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Alpha 1-Antitrypsin Deficiency
Intervention  ICMJE Drug: ARO-AAT Injection
solution for subcutaneous (sc) injection
Study Arms  ICMJE
  • Experimental: ARO-AAT Cohort 1

    Administered on Day 1, Weeks 4 and 16 for a minimum of 3 doses.

    Treatment Extension (optional enrollment): Administered every 12 weeks for 8 additional doses.

    Intervention: Drug: ARO-AAT Injection
  • Experimental: ARO-AAT Cohort 1b

    Administered on Day 1, Weeks 4 and 16, for a minimum of 3 doses.

    Treatment Extension (optional enrollment): Administered every 12 weeks for 8 additional doses.

    Intervention: Drug: ARO-AAT Injection
  • Experimental: ARO-AAT Cohort 2

    Administered on Day 1, Weeks 4, 16, 28 and 40 for a minimum of 5 doses.

    Treatment Extension (optional enrollment): Administered every 12 weeks for 8 additional doses.

    Intervention: Drug: ARO-AAT Injection
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 29, 2021)
16
Original Estimated Enrollment  ICMJE
 (submitted: May 9, 2019)
12
Estimated Study Completion Date  ICMJE August 23, 2023
Estimated Primary Completion Date August 23, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Diagnosis of AATD
  • Women of childbearing potential must have a negative pregnancy test, cannot be breast feeding, and must be willing to use contraception
  • Willing to provide written informed consent and to comply with study requirements
  • Non-smoker for at least 1 year
  • No abnormal finding of clinical relevance at screening

Exclusion Criteria:

  • Clinically significant health concerns other than AATD
  • Previous diagnosis or diagnosis at Screening of definitive liver cirrhosis
  • Regular use of alcohol within one month prior to Screening
  • Use of an investigational agent or device within 30 days prior to dosing or current participation in an investigational study involving therapeutic intervention
  • Use of illicit drugs within 1 year prior to Screening

Note: additional inclusion/exclusion criteria may apply, per protocol

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Germany,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03946449
Other Study ID Numbers  ICMJE AROAAT2002
2019-000068-86 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Arrowhead Pharmaceuticals
Study Sponsor  ICMJE Arrowhead Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Arrowhead Pharmaceuticals
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP