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Safety, Tolerability and Effect on Liver Histologic Parameters of ARO-AAT (SEQUOIA)

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ClinicalTrials.gov Identifier: NCT03945292
Recruitment Status : Recruiting
First Posted : May 10, 2019
Last Update Posted : July 11, 2019
Sponsor:
Information provided by (Responsible Party):
Arrowhead Pharmaceuticals

Study Description
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Brief Summary:
The purpose of AROAAT2001 (SEQUOIA) is to evaluate the safety, tolerability and effect on liver histologic parameters with administration of the investigational product, ARO-AAT, in participants with alpha-1 antitrypsin deficiency (AATD). Participants will receive multiple subcutaneous doses of ARO-AAT.

Condition or disease Intervention/treatment Phase
Alpha 1-Antitrypsin Deficiency Drug: ARO-AAT Injection Other: Placebo Phase 2 Phase 3

Detailed Description:
In Part A, participants will be enrolled to receive multiple doses of ARO-AAT or placebo at varying dose levels. Once Part A is complete, a single dose level for Part B will be selected based on safety and pharmacodynamic parameters from Part A. Patients enrolled into Part A will roll over to the Part B dose level or continue to receive placebo.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Placebo-Controlled, Multi-dose, Phase 2/3 Study to Determine the Safety, Tolerability and Effect on Liver Histologic Parameters in Response to ARO-AAT in Patients With Alpha-1 Antitrypsin Deficiency (AATD) [SEQUOIA]
Estimated Study Start Date : July 30, 2019
Estimated Primary Completion Date : May 1, 2023
Estimated Study Completion Date : May 1, 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: ARO-AAT

Part A: administered on Days 1, 29 and 113 and every 84 days thereafter until dose selected for Part B

Part B: minimum of 6, maximum of 9 doses

 Drug: ARO-AAT Injection
solution for subcutaneous (sc) injection
Placebo Comparator: Placebo

Part A: administered on Days 1, 29 and 113 and every 84 days thereafter until dose selected for Part B

Part B: minimum of 6, maximum of 9 doses

 Other: Placebo
sterile normal saline (0.9% NaCl), calculated to match active comparator, for sc injection


Outcome Measures
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Primary Outcome Measures :
  1. Part A: Percentage Change From Baseline in Soluble Liver Z-Alpha-1 Antitrypsin (Z-AAT), insoluble liver Z-AAT Levels at Day 113 [ Time Frame: Baseline, Day 113 ]
  2. Part A: Percentage Change From Baseline in Serum AAT Levels at Day 113 [ Time Frame: Baseline, Day 113 ]
  3. Part A:Number of Participants with Adverse Events (AEs) Possibly or Probably Related to Treatment [ Time Frame: Up to Day 113 ]
  4. Part B:Number of Participants Achieving a 2-Point Improvement in a Histologic Grading Scale of AATD Associated Liver Disease AND No Worsening of Liver Fibrosis Based on Ishak Score [ Time Frame: End of Study Biopsy (84 days +/- 14 days after last Part B dose) ]

Secondary Outcome Measures :
  1. Part B: Change from Baseline Over Time in a Histologic Grading Scale of AATD Associated Liver Disease [ Time Frame: Baseline, End of Study Biopsy (84 days +/- 14 days after last Part B dose) ]
  2. Part B: Number of Participants with Ishak Fibrosis Stage 1 or Greater Achieving at Least a 1-Stage Improvement [ Time Frame: End of Study Biopsy (84 days +/- 14 days after last Part B dose) ]
  3. Part B: Change from Baseline Over Time in Ishak Fibrosis Score [ Time Frame: Baseline, End of Study Biopsy (84 days +/- 14 days after last Part B dose) ]
  4. Part B: Number of Participants with AEs Possibly or Probably Related to Treatment [ Time Frame: Up Through End of Study Biopsy (84 days +/- 14 days after last Part B dose) ]

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of AATD
  • Liver biopsy at Screening indicating liver fibrosis
  • Women of childbearing potential must have a negative pregnancy test, cannot be breastfeeding, 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
  • Previous lung or liver transplant due to AATD
  • 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

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03945292


Contacts
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Contact: Medical Monitor 626-304-3400 medicalmonitor@arrowheadpharma.com

Locations
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United States, Alabama
University of Alabama at Birmingham Medical Center Not yet recruiting
Birmingham, Alabama, United States, 35233
Contact: Rakesha Garner    205-934-1224    rgarner@uabmc.edu   
Principal Investigator: Brendan McGuire, MD         
United States, Florida
University of Florida Hepatology Research at CTRB Recruiting
Gainesville, Florida, United States, 32610
Contact: Angie Bauer, RN    352-273-9512    bauera@medicine.ufl.edu   
Principal Investigator: Virginia Clark, MD         
United States, Iowa
University of Iowa Hospitals and Clinics Not yet recruiting
Iowa City, Iowa, United States, 52242
Contact: Donna Evans, RN    319-353-4574    donna-evans@uiowa.edu   
Principal Investigator: Arvind Murali, MD         
United States, South Carolina
Medical University of South Carolina (MUSC) Not yet recruiting
Charleston, South Carolina, United States, 29425
Contact: Gwen Blanton    843-792-8438    blantonm@musc.edu   
Principal Investigator: Charlton Strange, MD         
United States, Tennessee
Vanderbilt University Medical Center Not yet recruiting
Nashville, Tennessee, United States, 37232
Contact: Mary Vozar, RN    615-936-1745    Mary.c.vozar@vumc.org   
Principal Investigator: Michael Porayko, MD         
Sponsors and Collaborators
Arrowhead Pharmaceuticals
More Information
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Responsible Party: Arrowhead Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03945292     History of Changes
Other Study ID Numbers: AROAAT2001
2018-003385-14 ( EudraCT Number )
First Posted: May 10, 2019    Key Record Dates
Last Update Posted: July 11, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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

Additional relevant MeSH terms:
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Alpha 1-Antitrypsin Deficiency
Liver Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
 Genetic Diseases, Inborn
Subcutaneous Emphysema
Emphysema
Pathologic Processes