Alpha-1 Antitrypsin DeficiencyPhase 1NCT02363946
A Study of ARC-AAT in Healthy Volunteer Subjects and Patients With Alpha-1 Antitrypsin Deficiency (AATD)
A Phase 1 study testing ARC-AAT Injection and Diphenhydramine in people with Alpha-1 Antitrypsin Deficiency, run by Arrowhead Pharmaceuticals at 4 sites in 4 countries.
Trial summary
The purpose of the study is to determine the safety and tolerability of escalating doses of ARC-AAT and to evaluate the pharmacokinetics of ARC-AAT and the effect of ARC-AAT on circulating levels of alpha-1 antitrypsin (AAT). Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Alpha-1 Antitrypsin Deficiency
- What is being tested?
- ARC-AAT Injection and Diphenhydramine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 65 participants
- Where
- 4 sitesin 4 countries
- Study dates
- Feb 2015to Nov 2016
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- (Part A - Healthy Volunteers)
- Male or female healthy volunteers 18-50 years of age
- Written informed consent
- Body mass index between 18.0 and 28.0 kg/m2
- 12-lead electrocardiogram (ECG) at Screening and pre-dose assessment with no clinically significant abnormalities
- Non-pregnant/non-nursing females
Show all 18Show fewer
- Non-smoker for at least one year with current non-smoking status confirmed by urine cotinine
- Normal lung function (or not clinically significant per investigator assessment) based on spirometry and diffusion capacity of lung for carbon monoxide (DLCO) according to American Thoracic Society (ATS) - European Respiratory Society (ERS) criteria
- Highly effective, double barrier contraception (both male and female partners) during the study and for 3 months following the dose of ARC-AAT
- Willing and able to comply with all study assessments and adhere to protocol schedule
- Suitable venous access for blood sampling
- No abnormal finding of clinical relevance at screening
- Normal AAT level
- (Part B-Patients) - As for Part A with the following exceptions:
- Male or female patients 18-70 years of age
- Confirmed diagnosis of homozygous alpha 1-protease inhibitor deficiency (PiZZ genotype) not receiving alpha-1 antitrypsin augmentation therapy for more than 4 weeks
- BMI between 18.0 and 35.0 kg/m2
- Non-smoker for at least three years with current non-smoking status confirmed by urine cotinine
Who cannot join
- (Part A-Healthy Volunteers)
- Current regular smoker of cigarettes or cigars or was a regular smoker over the past 1 year
- Recent (within last 6 weeks) transfusion of fresh frozen plasma, platelets, or packed red blood cells, or anticipated need for transfusion during study
- Acute signs of hepatitis/other infection within 4 weeks of screening and/or baseline
- Concurrent anticoagulants
- Use of dietary and/or herbal supplements that can interfere with liver metabolism within 7 days of screening
Show all 37Show fewer
- Use of any drugs known to induce or inhibit hepatic drug metabolism within 14 days prior to study treatment
- Depot injection/implant of any drug other than birth control within 3 months prior to study treatment
- Diagnosis of diabetes mellitus or history of glucose intolerance
- 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), and/or history of delta virus hepatitis
- Uncontrolled hypertension (blood pressure > 150/100 mmHg)
- History of cardiac rhythm disturbances
- Family history of congenital long QT syndrome or unexplained sudden cardiac death
- Symptomatic heart failure (per New York Heart Association [NYHA] guidelines)
- Unstable angina, myocardial infarction, severe cardiovascular disease, transient ischemic attack (TIA) or cerebrovascular accident (CVA) within past 6 months
- History of malignancy within last 5 years except adequately treated basal cell carcinoma, squamous cell skin cancer, superficial bladder tumors, or in situ cervical cancer.
- History of major surgery within 3 months of screening
- Regular use of alcohol within 1 month prior to screening (i.e., more than fourteen units of alcohol per week)
- Evidence of acute inflammation, sepsis or hemolysis or clinical evidence of lower respiratory tract infection
- Diagnosis of significant psychiatric disorder
- Use of illicit drugs (such as cocaine, phencyclidine [PCP] and crack) within 1 year prior to screening or positive urine drug screen
- History of allergy or hypersensitivity reaction to bee venom
- Use of an investigational agent or device within 30 days prior to dosing or current participation in an investigational study
- Clinically significant history/presence of any gastrointestinal pathology, unresolved gastrointestinal symptoms, liver or kidney disease
- Other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs
- Any clinically significant history/presence of poorly controlled neurological, endocrinal, cardiovascular, pulmonary, hematological, immunologic, psychiatric, metabolic or other uncontrolled systemic disease
- Blood donation (500 mL) within 7 days prior to study treatment
- History of fever within 2 weeks of screening
- Concomitant medical/psychiatric condition or social situation that would affect compliance or result in additional safety risk
- Excessive exercise/physical activity within 3 days of screening or enrollment or planned during the study
- History of thromboembolic disease, stroke within 6 months of baseline, and/or concurrent anticoagulant medication(s)
- (Part B-Patients) - As for Part A with the following exceptions:
- History of major surgery within 2 months of Screening
- Forced expiratory volume at one second (FEV1) at baseline < 60%
- AATD patients with liver elastography score > 11 at Screening
Trial locations and contacts
4 sites in 4 countries.
4 sites in 4 countries
About this study
Official title: A Double-Blind, Placebo-Controlled, Dose-Escalating, Phase 1 Study to Determine the Safety, Tolerability, Pharmacokinetics and Effect of Circulating Alpha-1 Antitrypsin Levels of ARC-AAT in Healthy Volunteer Subjects and in Patients With Alpha-1 Antitrypsin Deficiency (AATD)
The purpose of the study is to determine the safety and tolerability of escalating doses of ARC-AAT and to evaluate the pharmacokinetics of ARC-AAT and the effect of ARC-AAT on circulating levels of alpha-1 antitrypsin (AAT). The study will consist of two parts, Part A (conducted in healthy volunteers) and Part B (conducted in AATD patients) at up to 9 escalating dose levels with 6 participants per dose level.
Read the detailed description
Healthy volunteers and AATD patients will be randomized to receive a single intravenous injection of either ARC-AAT or Placebo in double-blind fashion. Up to thirteen cohorts (6 participants per cohort) will be enrolled. Participants in all cohorts will be confined to the clinical facility beginning on Day -1 with discharge on Day 2. Escalation to the next dose level will proceed until a participant experiences a dose-limiting toxicity (DLT) or there is achievement of pre-determined threshold reductions in AAT levels. Dosing in participants with AATD will commence based on pre-determined threshold reductions in AAT levels for healthy volunteers. For each participant, the duration of the study clinic visits is up to 11 weeks, from Screening to the End-of-Study examination. However, including a Day 90 Follow-Up telephone call, the maximum study duration is approximately 20 weeks.
- Conditions
- Alpha-1 Antitrypsin Deficiency
- Being tested
- ARC-AAT Injection, Placebo, Diphenhydramine
- Keywords
- alpha-1 antitrypsin, AATD
- Medical subject headings
- alpha 1-Antitrypsin Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ARC-AAT InjectionDrug
Also called ARC-AAT
RNA interference-based, liver-targeted therapeutic
PlaceboOther
0.9 % normal saline
DiphenhydramineDrug
Diphenhydramine 50 mg p.o. was administered 2 hours (±30 minutes) pre-dose as antihistamine pre-treatment.
| Study group | Role | What they receive |
|---|---|---|
| Part A: 0.38 mg/kg | Experimental | Single dose administration of ARC-AAT intravenous (IV) injection, 0.38 mg/kg in healthy volunteers Receives: Drug: ARC-AAT Injection; Drug: Diphenhydramine |
| Part A: 1.0 mg/kg | Experimental | Single dose administration of ARC-AAT IV injection, 1.0 mg/kg in healthy volunteers Receives: Drug: ARC-AAT Injection; Drug: Diphenhydramine |
| Part A: 2.0 mg/kg | Experimental | Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in healthy volunteers Receives: Drug: ARC-AAT Injection; Drug: Diphenhydramine |
| Part A: 3.0 mg/kg | Experimental | Single dose administration of ARC-AAT IV injection, 3.0 mg/kg in healthy volunteers Receives: Drug: ARC-AAT Injection; Drug: Diphenhydramine |
| Part A: 4.0 mg/kg | Experimental | Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in healthy volunteers Receives: Drug: ARC-AAT Injection; Drug: Diphenhydramine |
| Part A: 5.0 mg/kg | Experimental | Single dose administration of ARC-AAT IV injection, 5.0 mg/kg in healthy volunteers Receives: Drug: ARC-AAT Injection; Drug: Diphenhydramine |
| Part A: 6.0 mg/kg | Experimental | Single dose administration of ARC-AAT IV injection, 6.0 mg/kg in healthy volunteers Receives: Drug: ARC-AAT Injection; Drug: Diphenhydramine |
| Part A: 7.0 mg/kg | Experimental | Single dose administration of ARC-AAT IV injection, 7.0 mg/kg in healthy volunteers Receives: Drug: ARC-AAT Injection; Drug: Diphenhydramine |
| Part A: 8.0 mg/kg | Experimental | Single dose administration of ARC-AAT IV injection, 8.0 mg/kg in healthy volunteers Receives: Drug: ARC-AAT Injection; Drug: Diphenhydramine |
| Part A: Placebo | Placebo comparator | Single dose administration of 0.9% normal saline IV injection in healthy volunteers Receives: Other: Placebo; Drug: Diphenhydramine |
| Part B: 2.0 mg/kg | Experimental | Single dose administration of ARC-AAT IV injection, 2.0 mg/kg in participants with AATD Receives: Drug: ARC-AAT Injection; Drug: Diphenhydramine |
| Part B: 4.0 mg/kg | Experimental | Single dose administration of ARC-AAT IV injection, 4.0 mg/kg in participants with AATD Receives: Drug: ARC-AAT Injection; Drug: Diphenhydramine |
| Part B: 6.0 mg/kg | Experimental | Single dose administration of ARC-AAT IV injection, 6.0 mg/kg in participants with AATD Receives: Drug: ARC-AAT Injection; Drug: Diphenhydramine |
| Part B: 7.0 mg/kg | Experimental | Single dose administration of ARC-AAT IV injection, 7.0 mg/kg in participants with AATD Receives: Drug: ARC-AAT Injection; Drug: Diphenhydramine |
| Part B: Placebo | Placebo comparator | Single dose administration of 0.9% normal saline IV injection in participants with AATD Receives: Other: Placebo; Drug: Diphenhydramine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs
An adverse event (AE) is defined as any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. TEAEs are defined as defined as AEs with onset after administration of the study drug, or when a preexisting medical condition increases in severity or frequency after study drug administration. SAEs are defined as is an AE that: results in death; is life-threatening; requires inpatient hospitalization or prolongation of an existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a medically important event or reaction.
Measured: From the first dose of study treatment through Day 29 ± 1 day
Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values
Laboratory values collected include: hematology (haemoglobin, lymphocytes, neutrophils, platelets, white cell count, monocytes); biochemistry (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, bilirubin, creatine kinase, creatinine, gamma-glutamyltransferase, fasting glucose, troponin I); coagulation parameters (fibrinogen, international normalized ratio); and C-reactive protein.
Measured: Day 1 through Day 29 ± 1 day
Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Vital Signs, Electrocardiograms (ECGs), Pulmonary Function, Physical Findings, and Other Observations
Values collected include: vital signs (clinically concerning or symptomatic treatment emergent changes in heart rate, systolic blood pressure, diastolic blood pressure, respiratory rate, or temperature); ECGs (clinically significant changes from baseline were observed for ventricular rate, RR interval, QRS duration, QT interval or QT interval corrected for heart rate using Fridericia's formula [QTcF]; treatment emergent clinically significant changes in ST segments, P wave or T wave morphology; cardiac telemetry monitoring); clinically significant abnormal physical examination findings; treatment emergent sensitivity to bee venom; pulmonary function (clinically significant worsening in spirometry parameters and carbon monoxide diffusing capacity of the lung for carbon monoxide [DLCO]).
Measured: Day 1 through Day 29 ± 1 day
Pharmacokinetics of ARC-AAT: Maximum Observed Plasma Concentration (Cmax) for the Analytes AD00370 and ARC-Melittin-Like Peptide (MLP; Part A)
Measured: Day 1, 2, and 3 at pre-dose and then at 0.08, 0.5, 1, 3, 6, 24 and 48 hours post-dose
Pharmacokinetics of ARC-AAT: Time to Maximum Observed Concentration (Tmax) for the Analytes AD00370 and ARC-MLP (Part A)
Measured: Day 1, 2, and 3 at pre-dose and then at 0.08, 0.5, 1, 3, 6, 24 and 48 hours post-dose
Pharmacokinetics of ARC-AAT: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Time 24 Hours (AUC0-24) for the Analytes AD00370 and ARC-MLP (Part A)
Measured: Day 1, 2, and 3 at pre-dose and then at 0.08, 0.5, 1, 3, 6, 24 and 48 hours post-dose
Pharmacokinetics of ARC-AAT: Area Under the Plasma Concentration Versus Time Curve From From Zero to Infinity (AUCinf) for the Analytes AD00370 and ARC-MLP (Part A)
Measured: Day 1, 2, and 3 at pre-dose and then at 0.08, 0.5, 1, 3, 6, 24 and 48 hours post-dose
Pharmacokinetics of ARC-AAT: Terminal Elimination Rate Constant Obtained From the Slope of the Line (Kel) for the Analytes AD00370 and ARC-MLP (Part A)
Measured: Day 1, 2, and 3 at pre-dose and then at 0.08, 0.5, 1, 3, 6, 24 and 48 hours post-dose
Pharmacokinetics of ARC-AAT: Half-Life (t1/2) for the Analytes AD00370 and ARC-MLP (Part A)
Measured: Day 1, 2, and 3 at pre-dose and then at 0.08, 0.5, 1, 3, 6, 24 and 48 hours post-dose
Percentage Reduction From Baseline of AAT Up to Day 29
Clinical assay for total serum AAT level was used for Part A. A quantitative measurement of AAT was used for Part B. A negative percent reduction indicates a percentage increase. Baseline AAT levels consisted of a geometric mean based on 3 assessments taken prior to study drug administration: at 2 time points during the Screening window at least 5 days apart, and on Day -1.
Measured: Baseline, Days 3, 8, 15, 22 and 29
Secondary outcomes (5)
Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence)
Data presents the study visit day upon which a participant had the first occurrence of AAT reduction of > 30% from Baseline, and the number of participants who had a > 30% reduction at any visit (overall). Baseline AAT levels consisted of a geometric mean based on 3 assessments taken prior to study drug administration: at 2 time points during the Screening window at least 5 days apart, and on Day -1.
Measured: Baseline, Days 3, 8, 15, 22 and 29
Maximum Percentage Reduction in Mean AAT (Nadir of Mean AAT)
Measured: Study Day for Nadir of Mean AAT: Day 8 (for Part B 2 mg/kg arm), Day 15 (for Part A 0.38 mg/kg, 2 mg/kg, 4 mg/ kg, Placebo arms; Part B 4 mg/kg, Placebo arms), Day 22 (Part A 3 mg/kg, 5 mg/kg, 6 mg/kg, 7 mg/kg arms), Day 29 (1 mg/kg, 8 mg/kg arms)
Number of Participants With a Return From Nadir AAT Blood Levels to Above Normal or Within 15% of Baseline in > 100 Days
Baseline AAT levels consisted of a geometric mean based on 3 assessments taken prior to study drug administration: at 2 time points during the Screening window at least 5 days apart, and on Day -1.
Measured: Baseline, up to Day 29, and through 100 days of follow-up
Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose
Measured: Pre-dose, 2 hours post-dose
Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose
Measured: Pre-dose, 2 hours post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Feb 2015 (estimated)
- Study startFeb 2015
- Primary completionNov 2016
- Study completionNov 2016
Why it stopped: Company decision to terminate the trial
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alpha-1 Antitrypsin DeficiencyStudies of the same condition, open and under way.
- More trials run by Arrowhead PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- Arrowhead Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02363946
- Sponsor's protocol ID
- ARCAAT-1001
- Other IDs
- U1111-1171-0247, 2015-001147-36, 2015
- Status last verified
- Dec 2025
- First submitted
- 2 Feb 2015
- Last updated
- 12 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Turner AM, Stolk J, Bals R, Lickliter JD, Hamilton J, Christianson DR, Given BD, Burdon JG, Loomba R, Stoller JK, Teckman JH. Hepatic-targeted RNA interference provides robust and persistent knockdown of alpha-1 antitrypsin levels in ZZ patients. J Hepatol. 2018 Aug;69(2):378-384. doi: 10.1016/j.jhep.2018.03.012. Epub 2018 Mar 21.
PubMed 29572094
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind, Placebo-Controlled, Dose-Escalating, Phase 1 Study to Determine the Safety, Tolerability, Pharmacokinetics and Effect of Circulating Alpha-1 Antitrypsin Levels of ARC-AAT in Healthy Volunteer Subjects and in Patients With Alpha-1 Antitrypsin Deficiency (AATD)
- ClinicalTrials.gov ID
- NCT02363946
- Acronym / sponsor ID
- ARCAAT-1001
- Conditions
- Alpha-1 Antitrypsin Deficiency
- Keywords
- alpha-1 antitrypsin, AATD
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Company decision to terminate the trial
- Enrolment
- 65 participants (actual)
- Lead sponsor
- Arrowhead PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Feb 2015
- Primary completion
- Nov 2016 (actual)
- Study completion
- Nov 2016 (actual)
- First posted
- 16 Feb 2015 (estimated)
- Results
- Posted 3 Aug 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to determine the safety and tolerability of escalating doses of ARC-AAT and to evaluate the pharmacokinetics of ARC-AAT and the effect of ARC-AAT on circulating levels of alpha-1 antitrypsin (AAT). The study will consist of two parts, Part A (conducted in healthy volunteers) and Part B (conducted in AATD patients) at up to 9 escalating dose levels with 6 participants per dose level.
Detailed description
Healthy volunteers and AATD patients will be randomized to receive a single intravenous injection of either ARC-AAT or Placebo in double-blind fashion. Up to thirteen cohorts (6 participants per cohort) will be enrolled. Participants in all cohorts will be confined to the clinical facility beginning on Day -1 with discharge on Day 2. Escalation to the next dose level will proceed until a participant experiences a dose-limiting toxicity (DLT) or there is achievement of pre-determined threshold reductions in AAT levels. Dosing in participants with AATD will commence based on pre-determined threshold reductions in AAT levels for healthy volunteers. For each participant, the duration of the study clinic visits is up to 11 weeks, from Screening to the End-of-Study examination. However, including a Day 90 Follow-Up telephone call, the maximum study duration is approximately 20 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 15
| Arm | Type | Receives |
|---|---|---|
| Part A: 0.38 mg/kg | Experimental | Drug: ARC-AAT Injection, Drug: DiphenhydramineSingle dose administration of ARC-AAT intravenous (IV) injection, 0.38 mg/kg in healthy volunteers |
| Part A: 1.0 mg/kg | Experimental | Drug: ARC-AAT Injection, Drug: DiphenhydramineSingle dose administration of ARC-AAT IV injection, 1.0 mg/kg in healthy volunteers |
| Part A: 2.0 mg/kg | Experimental | Drug: ARC-AAT Injection, Drug: DiphenhydramineSingle dose administration of ARC-AAT IV injection, 2.0 mg/kg in healthy volunteers |
| Part A: 3.0 mg/kg | Experimental | Drug: ARC-AAT Injection, Drug: DiphenhydramineSingle dose administration of ARC-AAT IV injection, 3.0 mg/kg in healthy volunteers |
| Part A: 4.0 mg/kg | Experimental | Drug: ARC-AAT Injection, Drug: DiphenhydramineSingle dose administration of ARC-AAT IV injection, 4.0 mg/kg in healthy volunteers |
| Part A: 5.0 mg/kg | Experimental | Drug: ARC-AAT Injection, Drug: DiphenhydramineSingle dose administration of ARC-AAT IV injection, 5.0 mg/kg in healthy volunteers |
| Part A: 6.0 mg/kg | Experimental | Drug: ARC-AAT Injection, Drug: DiphenhydramineSingle dose administration of ARC-AAT IV injection, 6.0 mg/kg in healthy volunteers |
| Part A: 7.0 mg/kg | Experimental | Drug: ARC-AAT Injection, Drug: DiphenhydramineSingle dose administration of ARC-AAT IV injection, 7.0 mg/kg in healthy volunteers |
| Part A: 8.0 mg/kg | Experimental | Drug: ARC-AAT Injection, Drug: DiphenhydramineSingle dose administration of ARC-AAT IV injection, 8.0 mg/kg in healthy volunteers |
| Part A: Placebo | Placebo comparator | Other: Placebo, Drug: DiphenhydramineSingle dose administration of 0.9% normal saline IV injection in healthy volunteers |
| Part B: 2.0 mg/kg | Experimental | Drug: ARC-AAT Injection, Drug: DiphenhydramineSingle dose administration of ARC-AAT IV injection, 2.0 mg/kg in participants with AATD |
| Part B: 4.0 mg/kg | Experimental | Drug: ARC-AAT Injection, Drug: DiphenhydramineSingle dose administration of ARC-AAT IV injection, 4.0 mg/kg in participants with AATD |
| Part B: 6.0 mg/kg | Experimental | Drug: ARC-AAT Injection, Drug: DiphenhydramineSingle dose administration of ARC-AAT IV injection, 6.0 mg/kg in participants with AATD |
| Part B: 7.0 mg/kg | Experimental | Drug: ARC-AAT Injection, Drug: DiphenhydramineSingle dose administration of ARC-AAT IV injection, 7.0 mg/kg in participants with AATD |
| Part B: Placebo | Placebo comparator | Other: Placebo, Drug: DiphenhydramineSingle dose administration of 0.9% normal saline IV injection in participants with AATD |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- (Part A - Healthy Volunteers)
- Male or female healthy volunteers 18-50 years of age
- Written informed consent
- Body mass index between 18.0 and 28.0 kg/m2
- 12-lead electrocardiogram (ECG) at Screening and pre-dose assessment with no clinically significant abnormalities
Key exclusion criteria (37 listed)
- (Part A-Healthy Volunteers)
- Current regular smoker of cigarettes or cigars or was a regular smoker over the past 1 year
- Recent (within last 6 weeks) transfusion of fresh frozen plasma, platelets, or packed red blood cells, or anticipated need for transfusion during study
- Acute signs of hepatitis/other infection within 4 weeks of screening and/or baseline
- Concurrent anticoagulants
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ARC-AAT InjectionAlso: ARC-AATRNA interference-based, liver-targeted therapeutic | Drug | Part A: 0.38 mg/kg, Part A: 1.0 mg/kg, Part A: 2.0 mg/kg, Part A: 3.0 mg/kg, Part A: 4.0 mg/kg, Part A: 5.0 mg/kg, Part A: 6.0 mg/kg, Part A: 7.0 mg/kg, Part A: 8.0 mg/kg, Part B: 2.0 mg/kg, Part B: 4.0 mg/kg, Part B: 6.0 mg/kg, Part B: 7.0 mg/kg |
| Placebo0.9 % normal saline | Other | Part A: Placebo, Part B: Placebo |
| DiphenhydramineDiphenhydramine 50 mg p.o. was administered 2 hours (±30 minutes) pre-dose as antihistamine pre-treatment. | Drug | Part A: 0.38 mg/kg, Part A: 1.0 mg/kg, Part A: 2.0 mg/kg, Part A: 3.0 mg/kg, Part A: 4.0 mg/kg, Part A: 5.0 mg/kg, Part A: 6.0 mg/kg, Part A: 7.0 mg/kg, Part A: 8.0 mg/kg, Part A: Placebo, Part B: 2.0 mg/kg, Part B: 4.0 mg/kg, Part B: 6.0 mg/kg, Part B: 7.0 mg/kg, Part B: Placebo |
Primary outcome
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs
Time frame: From the first dose of study treatment through Day 29 ± 1 day
An adverse event (AE) is defined as any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. TEAEs are defined as defined as AEs with onset after administration of the study drug, or when a preexisting medical condition increases in severity or frequency after study drug administration. SAEs are defined as is an AE that: results in death; is life-threatening; requires inpatient hospitalization or prolongation of an existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a medically important event or reaction.
Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Laboratory Values
Time frame: Day 1 through Day 29 ± 1 day
Laboratory values collected include: hematology (haemoglobin, lymphocytes, neutrophils, platelets, white cell count, monocytes); biochemistry (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, bilirubin, creatine kinase, creatinine, gamma-glutamyltransferase, fasting glucose, troponin I); coagulation parameters (fibrinogen, international normalized ratio); and C-reactive protein.
Number of Participants With Clinically Significant Treatment-Emergent Abnormalities in Vital Signs, Electrocardiograms (ECGs), Pulmonary Function, Physical Findings, and Other Observations
Time frame: Day 1 through Day 29 ± 1 day
Values collected include: vital signs (clinically concerning or symptomatic treatment emergent changes in heart rate, systolic blood pressure, diastolic blood pressure, respiratory rate, or temperature); ECGs (clinically significant changes from baseline were observed for ventricular rate, RR interval, QRS duration, QT interval or QT interval corrected for heart rate using Fridericia's formula [QTcF]; treatment emergent clinically significant changes in ST segments, P wave or T wave morphology; cardiac telemetry monitoring); clinically significant abnormal physical examination findings; treatment emergent sensitivity to bee venom; pulmonary function (clinically significant worsening in spirometry parameters and carbon monoxide diffusing capacity of the lung for carbon monoxide [DLCO]).
Pharmacokinetics of ARC-AAT: Maximum Observed Plasma Concentration (Cmax) for the Analytes AD00370 and ARC-Melittin-Like Peptide (MLP; Part A)
Time frame: Day 1, 2, and 3 at pre-dose and then at 0.08, 0.5, 1, 3, 6, 24 and 48 hours post-dose
Pharmacokinetics of ARC-AAT: Time to Maximum Observed Concentration (Tmax) for the Analytes AD00370 and ARC-MLP (Part A)
Time frame: Day 1, 2, and 3 at pre-dose and then at 0.08, 0.5, 1, 3, 6, 24 and 48 hours post-dose
Pharmacokinetics of ARC-AAT: Area Under the Plasma Concentration Versus Time Curve From Time 0 to Time 24 Hours (AUC0-24) for the Analytes AD00370 and ARC-MLP (Part A)
Time frame: Day 1, 2, and 3 at pre-dose and then at 0.08, 0.5, 1, 3, 6, 24 and 48 hours post-dose
Pharmacokinetics of ARC-AAT: Area Under the Plasma Concentration Versus Time Curve From From Zero to Infinity (AUCinf) for the Analytes AD00370 and ARC-MLP (Part A)
Time frame: Day 1, 2, and 3 at pre-dose and then at 0.08, 0.5, 1, 3, 6, 24 and 48 hours post-dose
Pharmacokinetics of ARC-AAT: Terminal Elimination Rate Constant Obtained From the Slope of the Line (Kel) for the Analytes AD00370 and ARC-MLP (Part A)
Time frame: Day 1, 2, and 3 at pre-dose and then at 0.08, 0.5, 1, 3, 6, 24 and 48 hours post-dose
Pharmacokinetics of ARC-AAT: Half-Life (t1/2) for the Analytes AD00370 and ARC-MLP (Part A)
Time frame: Day 1, 2, and 3 at pre-dose and then at 0.08, 0.5, 1, 3, 6, 24 and 48 hours post-dose
Percentage Reduction From Baseline of AAT Up to Day 29
Time frame: Baseline, Days 3, 8, 15, 22 and 29
Clinical assay for total serum AAT level was used for Part A. A quantitative measurement of AAT was used for Part B. A negative percent reduction indicates a percentage increase. Baseline AAT levels consisted of a geometric mean based on 3 assessments taken prior to study drug administration: at 2 time points during the Screening window at least 5 days apart, and on Day -1.
5 secondary outcomes
Number of Participants With AAT Reduction > 30% From Baseline (First Occurrence)
Time frame: Baseline, Days 3, 8, 15, 22 and 29
Maximum Percentage Reduction in Mean AAT (Nadir of Mean AAT)
Time frame: Study Day for Nadir of Mean AAT: Day 8 (for Part B 2 mg/kg arm), Day 15 (for Part A 0.38 mg/kg, 2 mg/kg, 4 mg/ kg, Placebo arms; Part B 4 mg/kg, Placebo arms), Day 22 (Part A 3 mg/kg, 5 mg/kg, 6 mg/kg, 7 mg/kg arms), Day 29 (1 mg/kg, 8 mg/kg arms)
Number of Participants With a Return From Nadir AAT Blood Levels to Above Normal or Within 15% of Baseline in > 100 Days
Time frame: Baseline, up to Day 29, and through 100 days of follow-up
Mean Percentage Change in Circulating Blood Levels of Cytokines 2 Hours Post-Dose
Time frame: Pre-dose, 2 hours post-dose
Mean Percentage Change in Circulating Blood Levels of Complement Factors 2 Hours Post-Dose
Time frame: Pre-dose, 2 hours post-dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29572094Turner AM, Stolk J, Bals R, Lickliter JD, Hamilton J, Christianson DR, Given BD, Burdon JG, Loomba R, Stoller JK, Teckman JH. Hepatic-targeted RNA interference provides robust and persistent knockdown of alpha-1 antitrypsin levels in ZZ patients. J Hepatol. 2018 Aug;69(2):378-384. doi: 10.1016/j.jhep.2018.03.012. Epub 2018 Mar 21.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ARC-AAT Injection and Diphenhydramine in people with Alpha-1 Antitrypsin Deficiency, run by Arrowhead Pharmaceuticals at 4 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Australia, Germany, Netherlands, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Aug 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), or Discontinuations Due to TEAEs (time frame: From the first dose of study treatment through Day 29 ± 1 day). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02363946, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jan 2026.