A clinical trial to assess the safety and effects of a novel medicine intended for the treatment of patients with liver disease due to Alpha-1 Antitrypsin Deficiency (AATD)
- Conditions
- alpha-1 antitrypsin deficiency (AATD)-associated liver diseaseMedDRA version: 23.1Level: LLTClassification code 10001806Term: Alpha-1 anti-trypsin deficiencySystem Organ Class: 100000004850Therapeutic area: Diseases [C] - Digestive System Diseases [C06]
- Registration Number
- EUCTR2018-003385-14-PT
- Lead Sponsor
- Arrowhead Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 36
1. Male or non-nursing female patients 18-75 years of age, inclusive, at the time of Screening with previous diagnosis of PiZZ genotype Alpha-1 Antitrypsin Deficiency. PiZZ diagnosis from source verifiable medical records is permitted. Otherwise, patients must undergo PiZZ confirmatory testing at Screening. PiMZ or PiSZ genotypes are not
permitted.
2. Able and willing to provide written informed consent prior to the performance of any study specific procedures.
3. Liver biopsy indicating a liver fibrosis score less than F4 based on local pathologist read.
a. A patient with no fibrosis may participate based in a previous biopsy conducted within one year if a source verifiable medical record specifies no evidence of fibrosis.
4. A 12-lead ECG at Screening that, in the opinion of the Investigator, has no new acute abnormalities (e.g., new onset atrial fibrillation) that compromise the patient's safety in this study. Stable disease (e.g., stable atrial fibrillation) is acceptable.
5. Non-smoker (defined as does not smoke cigarettes daily for at least 12 months) with current non-smoking status confirmed by urine cotinine at screening AND any previous smoking history prior to 12 months must be < 15 pack years. Patients may be on nicotine replacement (patch or gum). e-cigarettes (vapor) is not permitted. A positive urine cotinine result due to nicotine replacement is acceptable for enrollment at the discretion of the Investigator.
6. Use highly effective contraception during the study and for 3 months following the last dose of ARO-AAT. Males must not donate sperm for at least 3 months post last dose of study treatment. Females of childbearing potential must have a negative urine pregnancy test at Screening and on Day 1 pre-dose. Females not of childbearing potential must be post-menopausal (defined as cessation of regular menstrual periods for at least 12 months without an alternative medical cause), confirmed by follicle-stimulating hormone (FSH) consistent with postmenopausal state based on lab reference ranges.
•Using twice the normal protection of birth control by using a condom AND one other form of either birth control pills (The Pill), depot or injectable birth control, IUD (Intrauterine Device), birth Control Patch (e.g., Ortho Evra), NuvaRing®, OR Surgical sterilization as a single form of birth control: i.e., tubal ligation, hysterectomy, bilateral oophorectomy, vasectomy or equivalently effective surgical form of birth control, is acceptable.
•True abstinence for the duration of the study and 12 weeks after the dose of ARO-AAT is acceptable only when in line with the preferred and usual lifestyle of the patient. Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea methods are not considered true abstinence and are not acceptable methods of contraception.
*All laboratory tests used as inclusion criteria may be repeated once and the repeat value may be used for inclusion purposes.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 36
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 6
1. INR = 1.2 at Screening (one retest permitted). If based on opinion of Investigator and/or prescribing physician patient is appropriate for anticoagulant holiday, patient may stop taking anticoagulant for an appropriate washout period and if indicated a repeat INR within < 1.2 would be acceptable. Vitamin K may be used for reversal. If INR is not indicated (direct thrombin inhibitors or Xa inhibitors) then appropriate washout period alone may be acceptable. (Note: Anti-platelet agents, aspirin, clopidogrel or NSAIDS are acceptable but must be held 7 days before and 7 days after liver biopsy)
2. Platelet count < 150 x 109/L at Screening (one retest permitted)
3. ALT and AST levels > 250 U/L at Screening (one retest permitted)
4. eGFR < 60ml/min / 1.73m2 at Screening (one retest permitted)
5. FEV1 <65% of predicted (preferentially post-bronchodilatory reading) at Screening (one retest permitted)
6. Recent (last 3 months) pneumonia or lower respiratory infection (which must be verifiable from the medical record). Patient reported infection is not sufficient to meet this criterion.
7. Unavoidable exposure to inhaled environmental toxins that in the clinical judgement of the investigator could impair pulmonary function significantly over the course of the study.
8. Human immunodeficiency virus infection, as shown by the presence of anti-HIV antibody (sero-positive)
9. Seropositive for HBV (HBsAg positive at Screening) or HCV (detectable HCV RNA at Screening). Cured HCV (positive antibody test without detectable HCV RNA is acceptable).
10. Uncontrolled hypertension (Systolic BP > 170 and diastolic BP >100 mmHg at Screening). Patients may rescreen once BP is successfully controlled.
11. A history of torsades de pointes, ventricular rhythm disturbances (e.g., ventricular tachycardia or fibrillation), untreated heart block (excluding first-degree block, being PR interval prolongation only), congenital long QT syndrome or new acute ST segment elevation or depression or new acute Q wave on ECG. Stable atrial dysrhythmias (e.g., stable atrial fibrillation) are acceptable.
12. Symptomatic heart failure (per NYHA guidelines), unstable angina, myocardial infarction, severe cardiovascular disease (ejection fraction <
20%, transient ischemic attack (TIA) or cerebrovascular accident (CVA) within 6 months prior to Screening
13. History of malignancy within the last 1 year except for adequately treated basal cell carcinoma, squamous cell skin cancer, superficial
bladder tumors, or in situ cervical cancer. Patients with other curatively treated malignancies who have no evidence of metastatic disease and
>1-year disease-free interval may be entered following approval by the Medical Monitor
14. History of major surgery within the prior 1 month prior to Screening
15. Regular use of alcohol within one month prior to the Screening visit (i.e., more than 14 units of alcohol per week [1 Unit = 150 mL of wine, 360 mL of beer, or 45 mL of 40% alcohol])
16. Use of illicit drugs (such as cocaine, phencyclidine [PCP]) within 1 year prior to the Screening visit or positive urine drug screen at Screening (a urine drug screen positive for benzodiazepines, opioids or THC is acceptable for enrollment at the discretion of the Investigator). The patient may still be eligible at discretion of Medical Monitor and Investigator if positive urine drug screen is due to a prescription medication.
17. Use of an investigational agent or device within 30 days prior to dosing or c
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method