A Phase 2 interventional study of ARC-520 and entecavir in Hepatitis B and Hepatitis D, sponsored by Arrowhead Pharmaceuticals. Terminated at 33 sites in 8 countries. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-01-13.
Sponsored by Arrowhead Pharmaceuticals · Phase 2, Interventional, and Treatment
Patients with chronic HBV infection will receive either ARC-520 alone or ARC-520 in combination with other treatments such as entecavir (ENT) or tenofovir (TDF) and/or pegylated interferon (PEG IFN) alpha 2a therapy, and be evaluated for safety and efficacy.
This is a multicenter, open-label study of ARC-520 based treatment regimens administered to patients with HBeAg positive or HBeAg negative immune active chronic Hepatitis B Virus (HBV) infection of various genotypes, or patients with Hepatitis D Virus (HDV). Eligible patients naive to previous treatment, and who have signed an Ethics Committee - approved informed consent, will be enrolled and will receive ARC-520 alone or ARC-520 plus additional treatments such as entecavir (ETV) or tenofovir (TDF) and/or pegylated interferon alpha 2a (PEG IFN) therapy. The study may initially involve up to a total of 96 eligible chronic HBV and HDV infected patients. Patients in all cohorts will receive a total of 13 doses of ARC-520 at 2mg/kg or 4 mg/kg. Patients will undergo the following evaluations at regular intervals during the study: medical history, physical examinations, vital sign measurements (blood pressure, heart rate, respiratory rate, and temperature), weight, adverse events assessment (AEs), 12-lead ECGs, liver fibrosis testing, concomitant medication assessment, blood sample collection for hematology, coagulation, chemistry, exploratory Pharmacodynamic (PD) measures, urinalysis, HBV serology, cytokines, Follicle Stimulating Hormone (FSH) testing (post-menopausal females) and pregnancy testing for females of childbearing potential. Clinically significant changes including AEs will be followed until resolution, until the condition stabilizes, until the event is otherwise explained, or until the patient is lost to follow-up. For each patient, the duration of the study is approximately 96 weeks, from enrolment to last visit. Prior to enrolment there is a 60 day screening period. Addition of new cohorts and additional treatment regimens are anticipated for this study.
1,045 studies on the registry are indexed under Hepatitis B; 139 are open to participants now.
This study's enrollment of 79 is below the median of 147 across 756 interventional studies indexed under Hepatitis B.
Browse Hepatitis B studies →Arrowhead Pharmaceuticals is the lead sponsor of 50 studies on the registry; 9 are open to participants now.
Of its 24 completed or terminated interventional studies of FDA-regulated products, 12 (50%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Treatment-naïve, hepatitis B "e" antigen (HBeAg)-positive participants with chronic hepatitis B (CHB) of any genotype administered ARC-520 (2 mg/kg intravenous \[IV\]) every 4 weeks for 48 weeks (13 doses).
Drug: ARC-520 · Drug: antihistamine
Treatment-naïve, HBeAg-positive, Genotype B participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered peginterferon (PEG IFN) alpha 2a for 48 weeks starting Day 87.
Drug: ARC-520 · Drug: entecavir · Biological: pegylated interferon alpha 2a · Drug: tenofovir disoproxil · Drug: antihistamine
Treatment-naïve, HBeAg-negative, Genotype B participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.
Drug: ARC-520 · Drug: entecavir · Biological: pegylated interferon alpha 2a · Drug: tenofovir disoproxil · Drug: antihistamine
Treatment-naïve, HBeAg-positive, Genotype C participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.
Drug: ARC-520 · Drug: entecavir · Biological: pegylated interferon alpha 2a · Drug: tenofovir disoproxil · Drug: antihistamine
Treatment-naïve, HBeAg-negative, Genotype C participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.
Drug: ARC-520 · Drug: entecavir · Biological: pegylated interferon alpha 2a · Drug: tenofovir disoproxil · Drug: antihistamine
Treatment-naïve, HBeAg-negative, Genotype D participants with CHB administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) concomitantly with daily orally administered ETV or TDF for approximately 60 weeks starting Day 1 and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 87.
Drug: ARC-520 · Drug: entecavir · Biological: pegylated interferon alpha 2a · Drug: tenofovir disoproxil · Drug: antihistamine
Treatment-naïve, HBeAg-negative or HBeAg-positive participants with hepatitis delta virus (HDV) administered ARC-520 (2 mg/kg increasing to 4 mg/kg or 4 mg/kg IV) every 4 weeks for 48 weeks (13 doses) and weekly subcutaneously administered PEG IFN alpha 2a for 48 weeks starting Day 15.
Drug: ARC-520 · Biological: pegylated interferon alpha 2a · Drug: antihistamine
Treatment-naïve, HBeAg-positive participants with CHB of any genotype administered ARC-520 (4 mg/kg IV) every 4 weeks for 48 weeks (13 doses).
Drug: ARC-520 · Drug: antihistamine
ARC-520 will be administered intravenously concomitantly with 0.9% normal saline using an infusion rate of 0.4 mL/min (24 mL/hour) for study treatment and 200 mL/hr for saline.
0.5 mg once daily; oral
Also known as: Baraclude
180 mcg; subcutaneous injection once weekly
Also known as: Peginterferon, Pegasys
300 mg once daily; oral
Also known as: Viread
All participants will be pre-treated with an oral antihistamine selected by the investigator from the list of approved antihistamines that is available in that country. Acceptable antihistamines are: diphenhydramine 50 mg p.o., chlorpheniramine 8 mg p.o., hydroxyzine 50 mg p.o., or cetirizine 10 mg p.o.
Percentage of Participants Achieving a 1-log Reduction in Hepatitis B Surface Antigen (HBsAg) at Week 60 Compared to Baseline
The percentage of participants with chronic HBV achieving a 1-log reduction in HBsAg compared to baseline (mean of pre-dose values) at Week 60 after completion of 48 weeks of ARC-520 Injection.
Time frame: Baseline, Week 60
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs Considered Possibly or Probably Related to Treatment
The Principal Investigator (or medically qualified designee) will use clinical judgment to determine the relationship. An adverse event (AE) was considered "possibly related" when there is a reasonable possibility that the incident, experience, or outcome may have been caused by the product under investigation. An AE was considered "probably related" when there are facts, evidence, or arguments to suggest that the event is related to the product under investigation. Only AEs that occurred post-dose were considered treatment-emergent. Clinically significant abnormal laboratory findings or other abnormal assessments that are detected during the study or are present at baseline and significantly worsen following the start of the study will be reported as AEs.
Time frame: From first dose of study drug up to 36 weeks of treatment, plus up to 48 weeks of follow-up
Percentage of Participants With HBsAg Loss (Based on Qualitative Assay) Over Time
The qualitative HBsAg assay gives a binary result, positive or negative.
Time frame: Weeks 52, 60, 72 and 96
Percentage of Participants Achieving a 1-log Reduction in HBsAg and Achieving an HBsAg Level < 100 IU/L Over Time
Time frame: Weeks 52, 60, 72 and 96
Time to HBsAg Loss
Time frame: Baseline through Week 96
Time to Anti-HBs (Antibody to Hepatitis B Surface Antigen) Seroconversion
Time frame: Baseline through Week 96
Percentage of Participants With Anti-HBs Seroconversion Over Time
Time frame: Weeks 52, 60, 72 and 96
Percentage of Participants With HBeAg Loss and Anti-Hepatitis B e Antigen (Anti-HBe) Seroconversion (if HBeAg-Positive at Study Entry) Over Time
Time frame: Weeks 52, 60, 72 and 96
Percentage of Participants With Resistance to ARC-520 Injection by Week 52
Resistance is defined as \> 1.0 log IU/mL quantitative HBsAg (qHBsAg) increase from nadir, confirmed by repeat test.
Time frame: Week 52
Percentage of Participants With Resistance to the Combination Therapy From Baseline to Week 60
Resistance is defined as \> 1.0 log IU/mL increase in HBV DNA from nadir, confirmed by repeat test.
Time frame: Baseline, Week 60
Percentage of Participants With HDV With Undetectable HDV Ribonucleic Acid (RNA) After 48 Weeks of Concomitant ARC-520 Injection and PEG IFN Alpha 2a Therapy Over Time (Cohort 7 Only)
Time frame: Weeks 52, 60, 72 and 96
Log Change From Baseline in Quantitative HBV Deoxyribonucleic Acid (DNA) Serum Levels Over Time
Time frame: Baseline, Weeks 52, 60, 72 and 96
| Milestone | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Cohort 5 | Cohort 6 | Cohort 7 | Cohort 8 |
|---|---|---|---|---|---|---|---|---|
| Started | 10 | 2 | 7 | 12 | 11 | 13 | 12 | 12 |
| Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 10 | 2 | 7 | 12 | 11 | 13 | 12 | 12 |
| Withdrew: Adverse event | 1 | 0 | 2 | 0 | 1 | 0 | 0 | 0 |
| Withdrew: Withdrawal by subject | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Withdrew: Sponsor termination of the study | 9 | 2 | 5 | 12 | 10 | 12 | 12 | 12 |
The percentage of participants with chronic HBV achieving a 1-log reduction in HBsAg compared to baseline (mean of pre-dose values) at Week 60 after completion of 48 weeks of ARC-520 Injection.
No measurements were reported for this outcome.
The Principal Investigator (or medically qualified designee) will use clinical judgment to determine the relationship. An adverse event (AE) was considered "possibly related" when there is a reasonable possibility that the incident, experience, or outcome may have been caused by the product under investigation. An AE was considered "probably related" when there are facts, evidence, or arguments to suggest that the event is related to the product under investigation. Only AEs that occurred post-dose were considered treatment-emergent. Clinically significant abnormal laboratory findings or other abnormal assessments that are detected during the study or are present at baseline and significantly worsen following the start of the study will be reported as AEs.
| Participants | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Cohort 5 | Cohort 6 | Cohort 7 | Cohort 8 |
|---|---|---|---|---|---|---|---|---|
| Related TEAE | 1 | 0 | 3 | 2 | 3 | 4 | 3 | 3 |
| Related Serious TEAE | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
The qualitative HBsAg assay gives a binary result, positive or negative.
No measurements were reported for this outcome.
No measurements were reported for this outcome.
No measurements were reported for this outcome.
No measurements were reported for this outcome.
No measurements were reported for this outcome.
No measurements were reported for this outcome.
Resistance is defined as \> 1.0 log IU/mL quantitative HBsAg (qHBsAg) increase from nadir, confirmed by repeat test.
No measurements were reported for this outcome.
Resistance is defined as \> 1.0 log IU/mL increase in HBV DNA from nadir, confirmed by repeat test.
No measurements were reported for this outcome.
No measurements were reported for this outcome.
No measurements were reported for this outcome.
Collected over From first dose of study drug up to 36 weeks of treatment, plus up to 48 weeks of follow-up. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Cohort 1 | — | 0/10 (0%) | 5/10 (50%) |
| Cohort 2 | — | 0/2 (0%) | 0/2 (0%) |
| Cohort 3 | — | 0/7 (0%) | 4/7 (57.1%) |
| Cohort 4 | — | 0/12 (0%) | 5/12 (41.7%) |
| Cohort 5 | — | 0/11 (0%) | 5/11 (45.5%) |
| Cohort 6 | — | 1/13 (7.7%) | 8/13 (61.5%) |
| Cohort 7 | — | 0/12 (0%) | 9/12 (75%) |
| Cohort 8 | — | 0/12 (0%) | 6/12 (50%) |
| Event | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Cohort 5 | Cohort 6 | Cohort 7 | Cohort 8 |
|---|---|---|---|---|---|---|---|---|
| Vestibular neuronitisInfections and infestations | 0/10 | 0/2 | 0/7 | 0/12 | 0/11 | 1/13 | 0/12 | 0/12 |
| Event | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Cohort 5 | Cohort 6 | Cohort 7 | Cohort 8 |
|---|---|---|---|---|---|---|---|---|
| NeutropeniaBlood and lymphatic system disorders | 0/10 | 0/2 | 0/7 | 0/12 | 0/11 | 0/13 | 5/12 | 0/12 |
| LeukopeniaBlood and lymphatic system disorders | 0/10 | 0/2 | 0/7 | 0/12 | 0/11 | 0/13 | 4/12 | 0/12 |
| FatigueGeneral disorders | 0/10 | 0/2 | 2/7 | 0/12 | 3/11 | 3/13 | 0/12 | 1/12 |
| NauseaGastrointestinal disorders | 1/10 | 0/2 | 1/7 | 0/12 | 0/11 | 3/13 | 0/12 | 0/12 |
| DizzinessNervous system disorders | 2/10 | 0/2 | 0/7 | 0/12 | 1/11 | 1/13 | 0/12 | 2/12 |
| Viral infectionInfections and infestations | 0/10 | 0/2 | 1/7 | 1/12 | 2/11 | 0/13 | 0/12 | 0/12 |
| CoughRespiratory, thoracic and mediastinal disorders | 0/10 | 0/2 | 1/7 | 1/12 | 2/11 | 1/13 | 0/12 | 0/12 |
| LymphopeniaBlood and lymphatic system disorders | 0/10 | 0/2 | 0/7 | 0/12 | 0/11 | 0/13 | 2/12 | 0/12 |
| ThrombocytopeniaBlood and lymphatic system disorders | 0/10 | 0/2 | 0/7 | 0/12 | 0/11 | 0/13 | 2/12 | 0/12 |
| Upper respiratory tract infectionInfections and infestations | 1/10 | 0/2 | 0/7 | 0/12 | 1/11 | 2/13 | 0/12 | 2/12 |
| Age, Continuous(years) | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Cohort 5 | Cohort 6 | Cohort 7 | Cohort 8 | Total |
|---|---|---|---|---|---|---|---|---|---|
| Mean | 32.5 ± 11.09 | 29.5 ± 0.71 | 40.4 ± 7.37 | 36.3 ± 9.32 | 39.6 ± 12.61 | 38.2 ± 7.97 | 39.6 ± 7.73 | 36.7 ± 7.32 | 37.4 ± 9.17 |
| Sex: Female, Male(Participants) | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Cohort 5 | Cohort 6 | Cohort 7 | Cohort 8 | Total |
|---|---|---|---|---|---|---|---|---|---|
| Female | 7 | 1 | 4 | 6 | 3 | 2 | 6 | 5 | 34 |
| Male | 3 | 1 | 3 | 6 | 8 | 11 | 6 | 7 | 45 |
Ran from Dec 2015 to primary completion in Dec 2016, 12 months.
Results were first posted in Apr 2019, 2 years 4 months after primary completion.
How these figures are worked out, and which studies are left out of them.
This study is terminated, as verified in Dec 2025. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: ARC-520