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

Primary Purpose

Alpha-1 Antitrypsin Deficiency

Status
Withdrawn
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ARC-AAT Injection
Sponsored by
Arrowhead Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alpha-1 Antitrypsin Deficiency

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Inspiration Research Limited
  • Beaumont Hospital
  • IRCCS Policlinico San Matteo Foundation, University of Pavia
  • Skane University Hospital, Department of Gastroenterology

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ARC-AAT Injection

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
September 9, 2016
Last Updated
May 17, 2017
Sponsor
Arrowhead Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT02900183
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)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Withdrawn
Why Stopped
Company decision to not initiate trial
Study Start Date
October 2016 (Anticipated)
Primary Completion Date
November 2016 (Actual)
Study Completion Date
November 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Arrowhead Pharmaceuticals

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alpha-1 Antitrypsin Deficiency

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ARC-AAT Injection
Arm Type
Experimental
Arm Description
Intravenous administration of ARC-AAT Injection (4 mg/kg or 6 mg/kg) every 28 days for a total of 7 doses
Intervention Type
Drug
Intervention Name(s)
ARC-AAT Injection
Intervention Description
RNA interference (RNAi)-based, liver-targeted therapeutic
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
Change from baseline in circulating serum levels of alpha-1 antitrypsin
Time Frame
Baseline through Day 287 End-of Study Visit

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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
Facility Information:
Facility Name
Inspiration Research Limited
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5T3A9
Country
Canada
Facility Name
Beaumont Hospital
City
Dublin
Country
Ireland
Facility Name
IRCCS Policlinico San Matteo Foundation, University of Pavia
City
Pavia
ZIP/Postal Code
27100
Country
Italy
Facility Name
Skane University Hospital, Department of Gastroenterology
City
Malmo
ZIP/Postal Code
SE-205 02
Country
Sweden

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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