Alpha-1 Antitrypsin Deficiency related liver disease MedDRA version: 19.1 Level: PT Classification code 10001806 Term: Alpha-1 anti-trypsin deficiency System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: ARC-AAT Injection
Product Code: ARC-AAT
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: API-AAT
Current Sponsor code: API-AAT
Other descriptive name: API-AAT, A
Sponsors
Arrowhead Pharmaceuticals, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To be eligible for enrollment, participants must meet all of the following inclusion criteria: 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. Availability of documented PiZ phenotype is sufficient to allow enrollment but a confirmatory genotype must be performed. 2. Able and willing to provide written informed consent prior to the performance of any study specific procedures. 3. Participants with a BMI between 18.0 and 35.0 kg/m2, inclusive. Participants with BMI between 15-18 kg/m2 or between 35-40 kg/m2 may be enrolled at the PI’s discretion in consultation with Sponsor depending on co-morbidities. 4. A 12-lead ECG at Screening that, in the opinion of the investigator, has no abnormalities that compromise participant’s safety in this study. 5. Non-smoker (not a daily cigarette smoker) for at least 12 months with current non-smoking status confirmed by urine cotinine at screening. 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 PI. 6. Participants using 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. Males must not donate sperm for at least 3 months post last dose of study treatment. Male partners of female patients and female partners of male patients must also use contraception, if they are of childbearing potential. 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 postmenopausal (defined as cessation of regular menstrual periods for at least 12 months), confirmed by follicle-stimulating hormone (FSH) level > 40 mIU/mL or as otherwise 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 from the following: • Birth control pills (The Pill) • Depot or injectable birth control • IUD (Intrauterine Device) • Birth Control Patch (e.g., Othro Evra) • NuvaRing® • Surgical sterilization. i.e., tubal ligation, hysterectomy, bilateral oophorectomy, vasectomy or equivalently effective surgical form of birth control. Rhythm methods will not be considered as highly effective methods of birth control. 7. Participants who are willing and able to comply with all study assessments and adhere to the protocol schedule 8. Must have suitable venous access for blood sampling 9. No abnormal finding of clinical relevance at the Screening evaluation that in the opinion of the investigator could adversely impact subject safety during the study or adversely impact study results. 10. ALT, AST levels less than 5X times the upper limit of normal at Screening 11. Creatinine levels or equal to 60 at Screening 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 11 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 1
Exclusion criteria
Exclusion criteria: A potential participant will be excluded from the study if any of the following criteria apply: 1. INR > 1.3. If based on opinion of PI 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 170 and diastolic BP >100 mmHg at Screening) 8. A history of torsades de pointes, ventricular rhythm disturbances (e.g., ventricular tachycardia or fibrillation), pathologic sinus bradycardia (1 year disease-free interval may be entered following approval by the Medical Monitor 12. History of major surgery within 1 month of Screening 13. Regular use of alcohol within one month prior to the Screening visit (i.e., more than fourteen units of alcohol per week [1 Unit = 150 mL of wine, 360 mL of beer, or 45 mL of 40% alcohol]) 14. Use of illicit drugs (such as cocaine, phencyclidine [PCP] and crack) within 1 year prior to the Screening visit or positive urine drug screen at Screening (a urine drug screen positive for benzodiazepines, opioids or marijuana is acceptable for enrollment at the discretion of the PI) 15. History of known allergy to bee venom, any history of anaphylaxis or any history of severe systemic hypersensitivity reaction 16. Use of an investigational agent or device within 30 days prior to dosing or current participation in an investigational study involving a therapeutic intervention. Subjects who have participated in the ARCAAT-1001 study or observational studies are acceptable. 17. Any clinically significant history or presence of poorly controlled or decompensated neurological, endocrinal, cardiovascular, pulmonary, hematological, immunologic, psychiatric, metabolic or other uncontrolled systemic disease. 18. Blood donation (=500 mL) within 7 days prior to study trea
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the safety and tolerability of multiple doses of ARC-AAT Injection;Secondary Objective: To determine the effect of multiple doses of ARC-AAT Injection on circulating levels of alpha-1 antitrypsin;Primary end point(s): Safety and tolerability of repeated doses of ARC-AAT Injection. ;Timepoint(s) of evaluation of this end point: See Schedule of Assessments | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Serum alpha-1 antitrypsin levels;Timepoint(s) of evaluation of this end point: Pre-dose; Dosing Days 1, 29, 57, 85, 113, 141, 169; Days 197, 227, 257, 287 (EOS) | — |
Countries
Canada, Ireland, Sweden
Contacts
Public ContactSusan Boynton, Regulatory Affairs
Arrowhead Pharmaceuticals, Inc
Outcome results
None listed