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Trial record 4 of 128 for:    AAT

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 : August 12, 2019
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 August 12, 2019
Actual Study Start Date  ICMJE August 7, 2019
Estimated Primary Completion Date May 1, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 8, 2019)
  • 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 ]
  • Part A: Percentage Change From Baseline in Serum AAT Levels at Day 113 [ Time Frame: Baseline, Day 113 ]
  • Part A:Number of Participants with Adverse Events (AEs) Possibly or Probably Related to Treatment [ Time Frame: Up to Day 113 ]
  • 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) ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03945292 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 8, 2019)
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety, Tolerability and Effect on Liver Histologic Parameters of ARO-AAT
Official Title  ICMJE 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]
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Alpha 1-Antitrypsin Deficiency
Intervention  ICMJE
  • Drug: ARO-AAT Injection
    solution for subcutaneous (sc) injection
  • Other: Placebo
    sterile normal saline (0.9% NaCl), calculated to match active comparator, for sc injection
Study Arms  ICMJE
  • 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

    Intervention: Drug: ARO-AAT 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

    Intervention: Other: Placebo
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 8, 2019)
120
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 1, 2023
Estimated Primary Completion Date May 1, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

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: Medical Monitor 626-304-3400 medicalmonitor@arrowheadpharma.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03945292
Other Study ID Numbers  ICMJE AROAAT2001
2018-003385-14 ( EudraCT Number )
Has Data Monitoring Committee Yes
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 August 2019

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