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

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ClinicalTrials.gov Identifier: NCT02900183
Recruitment Status : Withdrawn (Company decision to not initiate trial)
First Posted : September 14, 2016
Last Update Posted : May 18, 2017
Sponsor:
Information provided by (Responsible Party):
Arrowhead Pharmaceuticals

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.

Condition or disease Intervention/treatment Phase
Alpha-1 Antitrypsin Deficiency Drug: ARC-AAT Injection Phase 2

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Estimated Study Start Date : October 2016
Actual Primary Completion Date : November 2016
Actual Study Completion Date : November 2016


Arm Intervention/treatment
Experimental: ARC-AAT Injection
Intravenous administration of ARC-AAT Injection (4 mg/kg or 6 mg/kg) every 28 days for a total of 7 doses
Drug: ARC-AAT Injection
RNA interference (RNAi)-based, liver-targeted therapeutic




Primary Outcome Measures :
  1. Incidence and frequency of adverse events as a measure of safety and tolerability of multiple doses of ARC-AAT Injection [ Time Frame: Baseline through Day 287 End-of Study Visit ]

Secondary Outcome Measures :
  1. Change from baseline in circulating serum levels of alpha-1 antitrypsin [ Time Frame: Baseline through Day 287 End-of Study Visit ]


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:

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

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): NCT02900183


Locations
Canada, Ontario
Inspiration Research Limited
Toronto, Ontario, Canada, M5T3A9
Ireland
Beaumont Hospital
Dublin, Ireland
Italy
IRCCS Policlinico San Matteo Foundation, University of Pavia
Pavia, Italy, 27100
Sweden
Skane University Hospital, Department of Gastroenterology
Malmo, Sweden, SE-205 02
Sponsors and Collaborators
Arrowhead Pharmaceuticals

Responsible Party: Arrowhead Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02900183     History of Changes
Other Study ID Numbers: ARCAAT2001
2016-000917-59 ( EudraCT Number )
First Posted: September 14, 2016    Key Record Dates
Last Update Posted: May 18, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Alpha 1-Antitrypsin Deficiency
Liver Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Subcutaneous Emphysema
Emphysema
Pathologic Processes
Alpha 1-Antitrypsin
Protein C Inhibitor
Trypsin Inhibitors
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action