Safety, Tolerability and Effect of ARC-AAT Injection on Circulating and Intrahepatic Alpha-1 Antitrypsin Levels

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Brief Title

Safety, Tolerability and Effect of ARC-AAT Injection on Circulating and Intrahepatic Alpha-1 Antitrypsin Levels

Official Title

An Open-Label, Multi-dose, Phase 2 Study to Determine the Safety, Tolerability and Effect on Circulating and Intrahepatic Alpha-1 Antitrypsin Levels of ARC-AAT as Evidenced by Changes in Liver Biopsy in Patients With Alpha-1 Antitrypsin Deficiency (AATD)

Brief Summary

      Patients with Alpha-1 Antitrypsin Deficiency (AATD) will be enrolled to receive multiple
      doses of ARC-AAT Injection. All subjects will require a pre-dose biopsy and a biopsy post
      last dose.

Detailed Description

      This is a multi-center, multi-dose study to evaluate the safety, tolerability and effect on
      intrahepatic and circulating Alpha-1 Antitrypsin (AAT) levels of ARC-AAT Injection,
      administered intravenously. Participants who have signed an Institutional Review Board/Ethics
      Committee (IRB/EC) approved informed consent form and met all of the protocol eligibility
      criteria will receive multiple intravenous doses (7 total doses administered every 28 days)
      of ARC-AAT Injection. Patients previously, currently or never receiving AAT augmentation
      therapy are acceptable for enrollment. All subjects will require a pre-dose biopsy and a
      post-dose biopsy completed after the last dose or at early termination as applicable. For
      each participant the duration of the study clinic visits is approximately 49 weeks, from the
      beginning of the Screening period to the Day 287 End-of-Study (EOS) visit.

      The following evaluations will be performed at regular intervals throughout the study:
      medical history, physical examinations, bee venom allergy blood test, vital sign measurements
      (blood pressure, temperature, heart rate, respiratory rate), weight, adverse events
      monitoring, electrocardiograms (ECGs), pregnancy tests (females), concurrent medication
      evaluation, pulmonary function testing, clinical laboratory tests including hematology,
      coagulation, chemistry, FibroTest, anti-drug antibodies, drug screens, serum AAT levels,
      liver biopsy, FibroScan, and urinalysis.

Study Phase

Phase 2

Study Type


Primary Outcome

Incidence and frequency of adverse events as a measure of safety and tolerability of multiple doses of ARC-AAT Injection

Secondary Outcome

 Change from baseline in circulating serum levels of alpha-1 antitrypsin


Alpha-1 Antitrypsin Deficiency


ARC-AAT Injection

Study Arms / Comparison Groups

 ARC-AAT Injection
Description:  Intravenous administration of ARC-AAT Injection (4 mg/kg or 6 mg/kg) every 28 days for a total of 7 doses


* 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


Estimated Enrollment


Start Date

October 2016

Completion Date

November 2016

Primary Completion Date

November 2016

Eligibility Criteria

        Inclusion Criteria:

          -  Male or non-nursing female patients 18-75 years of age, inclusive, at the time of

          -  Previous diagnosis of PiZZ genotype Alpha-1 Antitrypsin Deficiency (AATD)

          -  Non-smoker (not a daily cigarette smoker) for at least three years with current
             non-smoking status confirmed by urine cotinine at screening.

          -  Highly effective, double barrier contraception (both male and female partners) during
             the study and for 3 months following the last dose of ARC-AAT Injection

          -  Suitable venous access for blood sampling

        Exclusion Criteria:

          -  Known diagnosis of hepatic fibrosis from a cause other than AATD

          -  History of poorly controlled autoimmune disease, or any history of autoimmune

          -  Human immunodeficiency virus (HIV) infection

          -  Seropositive for Hepatitis B virus (HBV) or Hepatitis C virus (HCV)

          -  Uncontrolled hypertension

          -  History of cardiac rhythm disturbances

          -  Symptomatic heart failure, unstable angina, myocardial infarction, severe
             cardiovascular disease, transient ischemic attack (TIA) or cerebrovascular accident
             (CVA) within 6 months prior to study entry

          -  History of malignancy within the last 2 years except for adequately treated basal cell
             carcinoma, squamous cell skin cancer, superficial bladder tumors, or in situ cervical

          -  History of major surgery within 1 month of Screening

          -  Regular use of alcohol within one month prior to the Screening visit

          -  Use of illicit drugs (such as cocaine, phencyclidine [PCP] and crack) within 1 year
             prior to Screening or positive urine drug screen at Screening

          -  Use of an investigational agent or device within 30 days prior to dosing or current
             participation in an investigational study involving a therapeutic intervention

          -  Any clinically significant history/presence of an uncontrolled systemic disease

          -  Blood donation (≥500 mL) within 7 days prior to study treatment administration




18 Years - 75 Years

Accepts Healthy Volunteers



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Location Countries


Location Countries


Administrative Informations



Organization ID


Secondary IDs


Responsible Party


Study Sponsor

Arrowhead Pharmaceuticals

Study Sponsor

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Verification Date

May 2017