A Multi-dose Study of ARC-520 in Patients With Hepatitis B 'e' Antigen (HBeAg) Positive, Chronic Hepatitis B Virus Infection
Sponsor
Arrowhead Pharmaceuticals (Industry)
Overall Status
Terminated
CT.gov ID
NCT02604212
Collaborator
(none)
32
16
4
13
2
0.2
Study Details
Study Description
Brief Summary
Patients with HBeAG positive, chronic HBV infection will receive either ARC-520 or placebo in combination with entecavir or tenofovir, and be evaluated for safety and efficacy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
This is a multicenter, randomized, double-blind, placebo-controlled, multi-dose study of ARC-520 in combination with entecavir or tenofovir administered to patients with HBeAg positive and immune active chronic HBV infection Eligible patients who have signed an Ethics Committee - approved informed consent, will be enrolled and will receive ARC-520 or placebo in combination with entecavir or tenofovir. The study will enroll up to a total of 90 eligible chronic HBV infected patients. 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 electrocardiograms (ECGs), liver fibrosis testing, concomitant medication assessment, blood sample collection for hematology, coagulation, chemistry, lactate, Pharmacokinetic (PK) measures (in a subset of patients), exploratory Pharmacodynamic (PD) measures, urinalysis, HBV serology, 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 33 weeks from screening to the Day 169 follow-up visit. For patients enrolling into a planned extension study, the total duration of this study is approximately 25 weeks from screening to Day 113 end of study visit.
Study Design
Study Type:
Interventional
Actual Enrollment
:
32 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Randomized, Double-blind, Placebo-controlled Multi-dose Study to Determine the Depth of Hepatitis B Surface Antigen (HBsAg) Reduction Following Intravenous ARC-520 in Combination With Entecavir or Tenofovir in Patients With HBeAg Positive, Chronic Hepatitis B Virus (HBV) Infection
Study Start Date
:
Nov 1, 2015
Actual Primary Completion Date
:
Dec 1, 2016
Actual Study Completion Date
:
Dec 1, 2016
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo Low Dose Comparator Placebo (low dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) |
Other: Placebo
Drug: entecavir
All participants will take entecavir or tenofovir throughout the study. Participants will be instructed to take their medication daily.
Drug: antihistamine
All participants will be pretreated with an oral antihistamine. The antihistamine used should in general be an H1>H2 receptor blocker and would include diphenhydramine 50 mg, cetirizine 10 mg, chlorpheniramine 8 mg or hydroxyzine 50 mg. The Investigator is free to choose any of these antihistamines available locally and consistent with their country's Marketing Authorisation.
Drug: tenofovir
All participants will take entecavir or tenofovir throughout the study. Participants will be instructed to take their medication daily.
|
| Placebo Comparator: Placebo High Dose Comparator Placebo (high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) |
Other: Placebo
Drug: entecavir
All participants will take entecavir or tenofovir throughout the study. Participants will be instructed to take their medication daily.
Drug: antihistamine
All participants will be pretreated with an oral antihistamine. The antihistamine used should in general be an H1>H2 receptor blocker and would include diphenhydramine 50 mg, cetirizine 10 mg, chlorpheniramine 8 mg or hydroxyzine 50 mg. The Investigator is free to choose any of these antihistamines available locally and consistent with their country's Marketing Authorisation.
Drug: tenofovir
All participants will take entecavir or tenofovir throughout the study. Participants will be instructed to take their medication daily.
|
| Experimental: ARC-520 1.0 mg/kg Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) |
Drug: ARC-520
Drug: entecavir
All participants will take entecavir or tenofovir throughout the study. Participants will be instructed to take their medication daily.
Drug: antihistamine
All participants will be pretreated with an oral antihistamine. The antihistamine used should in general be an H1>H2 receptor blocker and would include diphenhydramine 50 mg, cetirizine 10 mg, chlorpheniramine 8 mg or hydroxyzine 50 mg. The Investigator is free to choose any of these antihistamines available locally and consistent with their country's Marketing Authorisation.
Drug: tenofovir
All participants will take entecavir or tenofovir throughout the study. Participants will be instructed to take their medication daily.
|
| Experimental: ARC-520 2.0 mg/kg High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) |
Drug: ARC-520
Drug: entecavir
All participants will take entecavir or tenofovir throughout the study. Participants will be instructed to take their medication daily.
Drug: antihistamine
All participants will be pretreated with an oral antihistamine. The antihistamine used should in general be an H1>H2 receptor blocker and would include diphenhydramine 50 mg, cetirizine 10 mg, chlorpheniramine 8 mg or hydroxyzine 50 mg. The Investigator is free to choose any of these antihistamines available locally and consistent with their country's Marketing Authorisation.
Drug: tenofovir
All participants will take entecavir or tenofovir throughout the study. Participants will be instructed to take their medication daily.
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) at Day 113 [Baseline, Day 113]
Change From Baseline in log qHBsAg at Day 113 in response to multiple doses of ARC-520 versus placebo, using a a mixed effect model for repeated measures (MMRM). Includes parameter baseline as a continuous covariate, and treatment and visit as fixed factors, interaction of treatment and visit, and interaction of parameter baseline and visit.
Secondary Outcome Measures
- Change From Baseline in Log qHBsAg Over Time [Baseline, Days 15, 29, 43, 57, 71, 85, 99]
Change From Baseline in log qHBsAg up to Day 99 in response to multiple doses of ARC-520 versus placebo, using a a mixed effect model for repeated measures (MMRM). Includes parameter baseline as a continuous covariate, and treatment and visit as fixed factors, interaction of treatment and visit, and interaction of parameter baseline and visit.
- Change From Baseline at Day 15 in Log qHBsAg, by Category [Baseline, Day 15]
Change in log qHBsAg from baseline, categorized into the following groups: no decrease, decrease > 0 to < 0.5 log IU/mL; decrease 0.5 to 1.0 log IU/mL; decrease > 1.0 log IU/mL, tabulated by dose and treatment for each visit.
- Change From Baseline at Day 29 in Log qHBsAg, by Category [Baseline, Day 29]
Change in log qHBsAg from baseline, categorized into the following groups: no decrease, decrease > 0 to < 0.5 log IU/mL; decrease 0.5 to 1.0 log IU/mL; decrease > 1.0 log IU/mL, tabulated by dose and treatment for each visit.
- Change From Baseline at Day 43 in Log qHBsAg, by Category [Baseline, Day 43]
Change in log qHBsAg from baseline, categorized into the following groups: no decrease, decrease > 0 to < 0.5 log IU/mL; decrease 0.5 to 1.0 log IU/mL; decrease > 1.0 log IU/mL, tabulated by dose and treatment for each visit.
- Change From Baseline at Day 57 in Log qHBsAg, by Category [Baseline, Day 57]
Change in log qHBsAg from baseline, categorized into the following groups: no decrease, decrease > 0 to < 0.5 log IU/mL; decrease 0.5 to 1.0 log IU/mL; decrease > 1.0 log IU/mL, tabulated by dose and treatment for each visit.
- Change From Baseline at Day 71 in Log qHBsAg, by Category [Baseline, Day 71]
Change in log qHBsAg from baseline, categorized into the following groups: no decrease, decrease > 0 to < 0.5 log IU/mL; decrease 0.5 to 1.0 log IU/mL; decrease > 1.0 log IU/mL, tabulated by dose and treatment for each visit.
- Change From Baseline at Day 85 in Log qHBsAg, by Category [Baseline, Day 85]
Change in log qHBsAg from baseline, categorized into the following groups: no decrease, decrease > 0 to < 0.5 log IU/mL; decrease 0.5 to 1.0 log IU/mL; decrease > 1.0 log IU/mL, tabulated by dose and treatment for each visit.
- Change From Baseline at Day 99 in Log qHBsAg, by Category [Baseline, Day 99]
Change in log qHBsAg from baseline, categorized into the following groups: no decrease, decrease > 0 to < 0.5 log IU/mL; decrease 0.5 to 1.0 log IU/mL; decrease > 1.0 log IU/mL, tabulated by dose and treatment for each visit.
- Change From Baseline at Day 113 in Log qHBsAg, by Category [Baseline, Day 113]
Change in log qHBsAg from baseline, categorized into the following groups: no decrease, decrease > 0 to < 0.5 log IU/mL; decrease 0.5 to 1.0 log IU/mL; decrease > 1.0 log IU/mL, tabulated by dose and treatment for each visit.
- Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and Discontinuations Due to AEs [Through Day 169 (± 3 days)]
An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. A treatment emergent AE (TEAE) was defined as an AE that was not present prior to the first study drug administration and started at/after the time of initiation of administration of study drug, or an AE which was present prior to initiation of study drug administration, which increased in severity after study drug administration. An SAE is any untoward medical occurrence that, at any dose: 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.
- Pharmacokinetics of ARC-520: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24) [Through 48 hours post-dosing on Day 1 and Day 85]
- Pharmacokinetics of ARC-520: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Quantifiable Plasma Concentration (AUClast) [Through 48 hours post-dosing on Day 1 and Day 85]
- Pharmacokinetics of ARC-520: Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUCinf) [Through 48 hours post-dosing on Day 1 and Day 85]
- Pharmacokinetics of ARC-520: Maximum Observed Plasma Concentration (Cmax) [Through 48 hours post-dosing on Day 1 and Day 85]
- Pharmacokinetics of ARC-520: Clearance (CL) [Through 48 hours post-dosing on Day 1 and Day 85]
- Pharmacokinetics of ARC-520: Apparent Volume of Distribution (V) [Through 48 hours post-dosing on Day 1 and Day 85]
- Pharmacokinetics of ARC-520: Terminal Elimination Rate Constant (Kel) [Through 48 hours post-dosing on Day 1 and Day 85]
- Pharmacokinetics of ARC-520: Terminal Elimination Half-Life (t1/2) [Through 48 hours post-dosing on Day 1 and Day 85]
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Male or female, 18 to 75 years of age.
-
Written informed consent.
-
No clinically significant abnormalities at screening/pre-dose 12-lead ECG assessment.
-
No new abnormal finding of clinical relevance at the screening evaluation.
-
Diagnosis of HBeAg positive, immune active, chronic HBV infection.
-
2months of continuous treatment with daily, oral entecavir or tenofovir.
-
Willingness to continue taking entecavir or tenofovir throughout the study.
-
Must use 2 effective methods of contraception (double barrier contraception or hormonal contraceptive along with a barrier contraceptive) (both male and female partners).
Exclusion Criteria:
-
Pregnant or lactating
-
Acute signs of hepatitis/other infection within 4 weeks of screening.
-
Antiviral therapy other than entecavir or tenofovir within 3 months of screening.
-
Prior treatment with interferon in the last 3 years.
-
Use within the last 6 months or anticipated requirement for anticoagulants, corticosteroids, immunomodulators, or immunosuppressants.
-
Use of prescription medication within 14 days prior to treatment administration except: topical products without systemic absorption, statins (except rosuvastatin), hypertension medications, or hormonal contraceptives.
-
Depot injection or implant of any drug within 3 months prior to treatment administration, except injectable/implantable birth control.
-
Diagnosis of diabetes mellitus.
-
History of autoimmune disease especially autoimmune hepatitis.
-
Human immunodeficiency virus (HIV) infection.
-
Sero-positive for Hepatitis C Virus (HCV), and/or a history of delta virus hepatitis.
-
Hypertension defined as blood pressure > 150/100 mmHg.
-
History of cardiac rhythm disturbances.
-
Family history or congenital long QT syndrome, Brugada syndrome or unexplained sudden cardiac death.
-
Symptomatic heart failure, unstable angina, myocardial infarction, severe cardiovascular disease within 6 months prior to study entry.
-
History of malignancy except for adequately treated basal cell carcinoma, squamous cell skin cancer, superficial bladder tumors, or in situ cervical cancer.
-
Has had a major surgery within 3 months of screening.
-
History of alcohol and/or drug abuse < 12 months from screening.
-
Regular uses of alcohol within 6 months prior to screening (ie, more than 14 units of alcohol per week).
-
Evidence of severe systemic acute inflammation, sepsis, or hemolysis.
-
Diagnosed with a significant psychiatric disorder.
-
Use of recreational drugs, such as marijuana, within 3 months prior to screening.
-
Use of drugs such as cocaine, phencyclidine (PCP), and methamphetamines, within 1 year prior to screening.
-
History of allergy to bee sting.
-
Use of investigational agents or devices within 30 days prior to planned study dosing or current participation in an investigational study.
-
Clinically significant history or presence of any gastrointestinal pathology, unresolved gastrointestinal symptoms, liver or kidney disease.
-
Presence of cholangitis, cholecystitis, cholestasis, or duct obstruction.
-
Clinically significant history or presence of poorly controlled/uncontrolled systemic disease.
-
History of fever within 2 weeks of screening.
-
Immunized with a live attenuated vaccine within 7 days prior to dosing or planned vaccination (excluding flu vaccine by injection).
-
Presence of any medical or psychiatric condition or social situation that impacts compliance or results in additional safety risk.
-
Participated in excessive exercise/physical activity within 7 days of screening or planned during the trial.
-
History of coagulopathy/stroke within past 6 months, and/or concurrent anticoagulant medication(s).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Queen Mary Hospital | Hong Kong | China | 999077 | |
| 2 | Prince of Wales Hospital | Hong Kong | China | ||
| 3 | Klinikum der Johann Wolfgang Goethe Universitaet | Frankfurt | Germany | 60590 | |
| 4 | Asklepios Klinik St. Georg - Chirurgisch-Traumatologisches Zentrum | Hamburg | Germany | 20099 | |
| 5 | Medizinische Hochschule Hannover | Hannover | Germany | 30625 | |
| 6 | Eugastro Gmbh | Leipzig | Germany | 04103 | |
| 7 | Universitaetsklinikum Leipzig | Leipzig | Germany | 4103 | |
| 8 | Klinikum Der Ludwig-Maximilian-Universitaet Muenchen | Muenchen | Germany | 81377 | |
| 9 | University Hospital of Tuebingen | Tuebingen | Germany | 72076 | |
| 10 | Universitaetsklinikum Ulm, Klinik fur Innere Medizin I | Ulm | Germany | 89081 | |
| 11 | Universitaetsklinikum Wuerzburg, Medizinische Klinik Und Poliklinik II | Wuerzburg | Germany | 97080 | |
| 12 | Pusan National University Hospital | Busan | Korea, Republic of | 602-739 | |
| 13 | Gachon University Gil Medical Center | Incheon | Korea, Republic of | 405-760 | |
| 14 | Seoul National University Hospital | Seoul | Korea, Republic of | 110-744 | |
| 15 | Severance Hospital, Yonsei University College of Medicine | Seoul | Korea, Republic of | 120-752 | |
| 16 | Pusan National University Yangsan Hospital | Yangsan-si Gyeongnam | Korea, Republic of | 626-770 |
Sponsors and Collaborators
- Arrowhead Pharmaceuticals
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Arrowhead Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02604212
Other Study ID Numbers:
- Heparc-2003
- 2014-004751-31
First Posted:
Nov 13, 2015
Last Update Posted:
Apr 16, 2019
Last Verified:
Jan 1, 2019
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Placebo Low Dose Comparator | Placebo High Dose Comparator | ARC-520 1.0 mg/kg | ARC-520 2.0 mg/kg |
|---|---|---|---|---|
| Arm/Group Description | Placebo (low dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | Placebo (high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) |
| Period Title: Overall Study | ||||
| STARTED | 6 | 5 | 10 | 11 |
| COMPLETED | 4 | 4 | 6 | 8 |
| NOT COMPLETED | 2 | 1 | 4 | 3 |
Baseline Characteristics
| Arm/Group Title | Placebo Low Dose Comparator | Placebo High Dose Comparator | ARC-520 1.0 mg/kg | ARC-520 2.0 mg/kg | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Placebo (low dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | Placebo (high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | Total of all reporting groups |
| Overall Participants | 6 | 5 | 10 | 11 | 32 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
39.8
(9.54)
|
45.0
(10.68)
|
42.1
(12.57)
|
41.6
(12.05)
|
42.0
(10.98)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
3
50%
|
1
20%
|
0
0%
|
6
54.5%
|
10
31.3%
|
| Male |
3
50%
|
4
80%
|
10
100%
|
5
45.5%
|
22
68.8%
|
Outcome Measures
| Title | Change From Baseline in Quantitative Hepatitis B Surface Antigen (Log qHBsAg) at Day 113 |
|---|---|
| Description | Change From Baseline in log qHBsAg at Day 113 in response to multiple doses of ARC-520 versus placebo, using a a mixed effect model for repeated measures (MMRM). Includes parameter baseline as a continuous covariate, and treatment and visit as fixed factors, interaction of treatment and visit, and interaction of parameter baseline and visit. |
| Time Frame | Baseline, Day 113 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat population: all participants who received at least 1 dose of study drug and had valid qHBsAg values at baseline and at least one time point on or after the Day 15 visit. |
| Arm/Group Title | Placebo | ARC-520 1.0 mg/kg | ARC-520 2.0 mg/kg |
|---|---|---|---|
| Arm/Group Description | Placebo (low or high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) |
| Measure Participants | 6 | 6 | 8 |
| Least Squares Mean (Standard Error) [log IU/mL] |
-0.104
(0.073)
|
-0.146
(0.065)
|
-0.542
(0.061)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, ARC-520 1.0 mg/kg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6815 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.042 | |
| Confidence Interval |
(2-Sided) 95% -0.243 to 0.159 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.102 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, ARC-520 2.0 mg/kg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <.0001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.438 | |
| Confidence Interval |
(2-Sided) 95% -0.638 to -0.237 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.101 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | ARC-520 1.0 mg/kg, ARC-520 2.0 mg/kg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <.0001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.396 | |
| Confidence Interval |
(2-Sided) 95% -0.569 to -0.223 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.088 |
|
| Estimation Comments | ||
| Title | Change From Baseline in Log qHBsAg Over Time |
|---|---|
| Description | Change From Baseline in log qHBsAg up to Day 99 in response to multiple doses of ARC-520 versus placebo, using a a mixed effect model for repeated measures (MMRM). Includes parameter baseline as a continuous covariate, and treatment and visit as fixed factors, interaction of treatment and visit, and interaction of parameter baseline and visit. |
| Time Frame | Baseline, Days 15, 29, 43, 57, 71, 85, 99 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat population: all participants who received at least 1 dose of study drug and had valid qHBsAg values at baseline and at least one time point on or after the Day 15 visit. |
| Arm/Group Title | Placebo | ARC-520 1.0 mg/kg | ARC-520 2.0 mg/kg |
|---|---|---|---|
| Arm/Group Description | Placebo (low dose or high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) |
| Measure Participants | 10 | 10 | 10 |
| Day 15 |
3.734
(0.519)
|
3.069
(0.654)
|
3.000
(0.411)
|
| Day 29 |
3.692
(0.588)
|
3.148
(0.658)
|
3.027
(0.395)
|
| Day 43 |
3.812
(0.463)
|
3.097
(0.664)
|
2.893
(0.436)
|
| Day 57 |
3.793
(0.507)
|
3.148
(0.651)
|
2.882
(0.437)
|
| Day 71 |
3.756
(0.489)
|
3.088
(0.626)
|
2.714
(0.477)
|
| Day 85 |
3.743
(0.543)
|
3.198
(0.610)
|
2.698
(0.466)
|
| Day 99 |
3.767
(0.541)
|
3.048
(0.593)
|
2.606
(0.477)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, ARC-520 1.0 mg/kg |
|---|---|---|
| Comments | Day 15 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0131 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.208 | |
| Confidence Interval |
(2-Sided) 95% -0.372 to -0.044 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.083 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, ARC-520 2.0 mg/kg |
|---|---|---|
| Comments | Day 15 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0036 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.247 | |
| Confidence Interval |
(2-Sided) 95% -0.412 to -0.082 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.084 |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | ARC-520 1.0 mg/kg, ARC-520 2.0 mg/kg |
|---|---|---|
| Comments | Day 15 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6136 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.039 | |
| Confidence Interval |
(2-Sided) 95% -0.192 to 0.113 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.077 |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Placebo, ARC-520 1.0 mg/kg |
|---|---|---|
| Comments | Day 29 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3104 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.085 | |
| Confidence Interval |
(2-Sided) 95% -0.249 to 0.080 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.083 |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Placebo, ARC-520 2.0 mg/kg |
|---|---|---|
| Comments | Day 29 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0401 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.174 | |
| Confidence Interval |
(2-Sided) 95% -0.340 to -0.008 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.084 |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | ARC-520 1.0 mg/kg, ARC-520 2.0 mg/kg |
|---|---|---|
| Comments | Day 29 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2494 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.089 | |
| Confidence Interval |
(2-Sided) 95% -0.242 to 0.063 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.077 |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Placebo, ARC-520 1.0 mg/kg |
|---|---|---|
| Comments | Day 43 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0149 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.211 | |
| Confidence Interval |
(2-Sided) 95% -0.380 to -0.042 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.085 |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Placebo, ARC-520 2.0 mg/kg |
|---|---|---|
| Comments | Day 43 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0003 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.319 | |
| Confidence Interval |
(2-Sided) 95% -0.489 to -0.149 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.086 |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | ARC-520 1.0 mg/kg, ARC-520 2.0 mg/kg |
|---|---|---|
| Comments | Day 29 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1655 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.108 | |
| Confidence Interval |
(2-Sided) 95% -0.262 to 0.045 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.078 |
|
| Estimation Comments | ||
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | Placebo, ARC-520 1.0 mg/kg |
|---|---|---|
| Comments | Day 57 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0889 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.150 | |
| Confidence Interval |
(2-Sided) 95% -0.324 to 0.023 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.088 |
|
| Estimation Comments | ||
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Placebo, ARC-520 2.0 mg/kg |
|---|---|---|
| Comments | Day 57 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0004 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.322 | |
| Confidence Interval |
(2-Sided) 95% -0.497 to -0.147 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.088 |
|
| Estimation Comments | ||
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | ARC-520 1.0 mg/kg, ARC-520 2.0 mg/kg |
|---|---|---|
| Comments | Day 57 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0298 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.172 | |
| Confidence Interval |
(2-Sided) 95% -0.326 to -0.017 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.078 |
|
| Estimation Comments | ||
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | Placebo, ARC-520 1.0 mg/kg |
|---|---|---|
| Comments | Day 71 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0415 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.184 | |
| Confidence Interval |
(2-Sided) 95% -0.361 to -0.007 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.089 |
|
| Estimation Comments | ||
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | Placebo, ARC-520 2.0 mg/kg |
|---|---|---|
| Comments | Day 71 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <.0001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.441 | |
| Confidence Interval |
(2-Sided) 95% -0.620 to -0.261 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.091 |
|
| Estimation Comments | ||
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | ARC-520 1.0 mg/kg, ARC-520 2.0 mg/kg |
|---|---|---|
| Comments | Day 71 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0015 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.257 | |
| Confidence Interval |
(2-Sided) 95% -0.413 to -0.100 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.079 |
|
| Estimation Comments | ||
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | Placebo, ARC-520 1.0 mg/kg |
|---|---|---|
| Comments | Day 85 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3510 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.086 | |
| Confidence Interval |
(2-Sided) 95% -0.268 to 0.096 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.092 |
|
| Estimation Comments | ||
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Placebo, ARC-520 2.0 mg/kg |
|---|---|---|
| Comments | Day 85 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <.0001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.404 | |
| Confidence Interval |
(2-Sided) 95% -0.590 to -0.219 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.094 |
|
| Estimation Comments | ||
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | ARC-520 1.0 mg/kg, ARC-520 2.0 mg/kg |
|---|---|---|
| Comments | Day 85 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0002 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.318 | |
| Confidence Interval |
(2-Sided) 95% -0.481 to -0.156 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.082 |
|
| Estimation Comments | ||
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | Placebo, ARC-520 1.0 mg/kg |
|---|---|---|
| Comments | Day 99 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1198 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.151 | |
| Confidence Interval |
(2-Sided) 95% -0.341 to 0.040 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.096 |
|
| Estimation Comments | ||
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | Placebo, ARC-520 2.0 mg/kg |
|---|---|---|
| Comments | Day 99 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <.0001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.516 | |
| Confidence Interval |
(2-Sided) 95% -0.708 to -0.325 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.097 |
|
| Estimation Comments | ||
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | ARC-520 1.0 mg/kg, ARC-520 2.0 mg/kg |
|---|---|---|
| Comments | Day 99 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <.0001 |
| Comments | ||
| Method | MMRM | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.366 | |
| Confidence Interval |
(2-Sided) 95% -0.535 to -0.197 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.085 |
|
| Estimation Comments | ||
| Title | Change From Baseline at Day 15 in Log qHBsAg, by Category |
|---|---|
| Description | Change in log qHBsAg from baseline, categorized into the following groups: no decrease, decrease > 0 to < 0.5 log IU/mL; decrease 0.5 to 1.0 log IU/mL; decrease > 1.0 log IU/mL, tabulated by dose and treatment for each visit. |
| Time Frame | Baseline, Day 15 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat population: all participants who received at least 1 dose of study drug and had valid qHBsAg values at baseline and at least one time point on or after the Day 15 visit. |
| Arm/Group Title | Placebo | ARC-520 1.0 mg/kg | ARC-520 2.0 mg/kg |
|---|---|---|---|
| Arm/Group Description | Placebo (low dose or high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) |
| Measure Participants | 10 | 10 | 10 |
| No Decrease |
0.026
(0.015)
|
0.032
(0.035)
|
|
| Decrease > 0 to < 0.5 log IU/mL |
-0.035
(0.014)
|
-0.153
(0.144)
|
-0.266
(0.192)
|
| Decrease 0.5 to 1.0 log IU/mL |
-0.707
(NA)
|
-0.666
(NA)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, ARC-520 1.0 mg/kg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0867 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, ARC-520 2.0 mg/kg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6285 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | ARC-520 1.0 mg/kg, ARC-520 2.0 mg/kg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7214 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Title | Change From Baseline at Day 29 in Log qHBsAg, by Category |
|---|---|
| Description | Change in log qHBsAg from baseline, categorized into the following groups: no decrease, decrease > 0 to < 0.5 log IU/mL; decrease 0.5 to 1.0 log IU/mL; decrease > 1.0 log IU/mL, tabulated by dose and treatment for each visit. |
| Time Frame | Baseline, Day 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat population: all participants who received at least 1 dose of study drug and had valid qHBsAg values at baseline and at least one time point on or after the Day 15 visit. |
| Arm/Group Title | Placebo | ARC-520 1.0 mg/kg | ARC-520 2.0 mg/kg |
|---|---|---|---|
| Arm/Group Description | Placebo (low dose or high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) |
| Measure Participants | 9 | 10 | 10 |
| No Decrease |
0.048
(0.043)
|
0.064
(NA)
|
|
| Decrease > 0 to < 0.5 log IU/mL |
-0.084
(0.078)
|
-0.129
(0.083)
|
-0.251
(0.190)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, ARC-520 1.0 mg/kg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0325 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, ARC-520 2.0 mg/kg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1409 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | ARC-520 1.0 mg/kg, ARC-520 2.0 mg/kg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Title | Change From Baseline at Day 43 in Log qHBsAg, by Category |
|---|---|
| Description | Change in log qHBsAg from baseline, categorized into the following groups: no decrease, decrease > 0 to < 0.5 log IU/mL; decrease 0.5 to 1.0 log IU/mL; decrease > 1.0 log IU/mL, tabulated by dose and treatment for each visit. |
| Time Frame | Baseline, Day 43 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat population: all participants who received at least 1 dose of study drug and had valid qHBsAg values at baseline and at least one time point on or after the Day 15 visit. |
| Arm/Group Title | Placebo | ARC-520 1.0 mg/kg | ARC-520 2.0 mg/kg |
|---|---|---|---|
| Arm/Group Description | Placebo (low dose or high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) |
| Measure Participants | 8 | 9 | 10 |
| No Decrease |
0.022
(0.012)
|
0.017
(NA)
|
|
| 1 participant analyDecrease > 0 to < 0.5 log IU/mL |
-0.050
(0.051)
|
-0.226
(0.077)
|
-0.275
(0.137)
|
| Decrease 0.5 to 1.0 log IU/mL |
-0.633
(0.141)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, ARC-520 1.0 mg/kg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0824 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, ARC-520 2.0 mg/kg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2217 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | ARC-520 1.0 mg/kg, ARC-520 2.0 mg/kg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1409 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Title | Change From Baseline at Day 57 in Log qHBsAg, by Category |
|---|---|
| Description | Change in log qHBsAg from baseline, categorized into the following groups: no decrease, decrease > 0 to < 0.5 log IU/mL; decrease 0.5 to 1.0 log IU/mL; decrease > 1.0 log IU/mL, tabulated by dose and treatment for each visit. |
| Time Frame | Baseline, Day 57 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat population: all participants who received at least 1 dose of study drug and had valid qHBsAg values at baseline and at least one time point on or after the Day 15 visit. |
| Arm/Group Title | Placebo | ARC-520 1.0 mg/kg | ARC-520 2.0 mg/kg |
|---|---|---|---|
| Arm/Group Description | Placebo (low dose or high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) |
| Measure Participants | 7 | 9 | 10 |
| No Decrease |
0.027
(0.012)
|
||
| 1 participant analyDecrease > 0 to < 0.5 log IU/mL |
-0.067
(0.072)
|
-0.176
(0.049)
|
-0.276
(0.156)
|
| Decrease 0.5 to 1.0 log IU/mL |
-0.571
(0.060)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, ARC-520 1.0 mg/kg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0625 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, ARC-520 2.0 mg/kg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0684 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | ARC-520 1.0 mg/kg, ARC-520 2.0 mg/kg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2105 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Title | Change From Baseline at Day 71 in Log qHBsAg, by Category |
|---|---|
| Description | Change in log qHBsAg from baseline, categorized into the following groups: no decrease, decrease > 0 to < 0.5 log IU/mL; decrease 0.5 to 1.0 log IU/mL; decrease > 1.0 log IU/mL, tabulated by dose and treatment for each visit. |
| Time Frame | Baseline, Day 71 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat population: all participants who received at least 1 dose of study drug and had valid qHBsAg values at baseline and at least one time point on or after the Day 15 visit. |
| Arm/Group Title | Placebo | ARC-520 1.0 mg/kg | ARC-520 2.0 mg/kg |
|---|---|---|---|
| Arm/Group Description | Placebo (low dose or high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) |
| Measure Participants | 7 | 9 | 9 |
| No Decrease |
0.011
(0.012)
|
||
| 1 participant analyDecrease > 0 to < 0.5 log IU/mL |
-0.094
(0.079)
|
-0.235
(0.086)
|
-0.296
(0.119)
|
| Decrease 0.5 to 1.0 log IU/mL |
-0.662
(0.140)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, ARC-520 1.0 mg/kg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1750 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, ARC-520 2.0 mg/kg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0229 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | ARC-520 1.0 mg/kg, ARC-520 2.0 mg/kg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0294 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Title | Change From Baseline at Day 85 in Log qHBsAg, by Category |
|---|---|
| Description | Change in log qHBsAg from baseline, categorized into the following groups: no decrease, decrease > 0 to < 0.5 log IU/mL; decrease 0.5 to 1.0 log IU/mL; decrease > 1.0 log IU/mL, tabulated by dose and treatment for each visit. |
| Time Frame | Baseline, Day 85 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat population: all participants who received at least 1 dose of study drug and had valid qHBsAg values at baseline and at least one time point on or after the Day 15 visit. |
| Arm/Group Title | Placebo | ARC-520 1.0 mg/kg | ARC-520 2.0 mg/kg |
|---|---|---|---|
| Arm/Group Description | Placebo (low dose or high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) |
| Measure Participants | 7 | 7 | 8 |
| No Decrease |
0.009
(0.010)
|
||
| 1 participant analyDecrease > 0 to < 0.5 log IU/mL |
-0.112
(0.147)
|
-0.171
(0.037)
|
-0.293
(0.112)
|
| Decrease 0.5 to 1.0 log IU/mL |
-0.684
(0.179)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, ARC-520 1.0 mg/kg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.4615 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, ARC-520 2.0 mg/kg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0508 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | ARC-520 1.0 mg/kg, ARC-520 2.0 mg/kg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0769 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Title | Change From Baseline at Day 99 in Log qHBsAg, by Category |
|---|---|
| Description | Change in log qHBsAg from baseline, categorized into the following groups: no decrease, decrease > 0 to < 0.5 log IU/mL; decrease 0.5 to 1.0 log IU/mL; decrease > 1.0 log IU/mL, tabulated by dose and treatment for each visit. |
| Time Frame | Baseline, Day 99 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat population: all participants who received at least 1 dose of study drug and had valid qHBsAg values at baseline and at least one time point on or after the Day 15 visit. |
| Arm/Group Title | Placebo | ARC-520 1.0 mg/kg | ARC-520 2.0 mg/kg |
|---|---|---|---|
| Arm/Group Description | Placebo (low dose or high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) |
| Measure Participants | 7 | 6 | 8 |
| No Decrease |
0.027
(0.018)
|
||
| 1 participant analyDecrease > 0 to < 0.5 log IU/mL |
-0.160
(0.202)
|
-0.210
(0.070)
|
-0.343
(0.110)
|
| Decrease 0.5 to 1.0 log IU/mL |
-0.652
(0.068)
|
||
| Decrease > 1.0 log IU/mL |
-1.011
(NA)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, ARC-520 1.0 mg/kg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0699 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, ARC-520 2.0 mg/kg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0179 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | ARC-520 1.0 mg/kg, ARC-520 2.0 mg/kg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0430 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Title | Change From Baseline at Day 113 in Log qHBsAg, by Category |
|---|---|
| Description | Change in log qHBsAg from baseline, categorized into the following groups: no decrease, decrease > 0 to < 0.5 log IU/mL; decrease 0.5 to 1.0 log IU/mL; decrease > 1.0 log IU/mL, tabulated by dose and treatment for each visit. |
| Time Frame | Baseline, Day 113 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat population: all participants who received at least 1 dose of study drug and had valid qHBsAg values at baseline and at least one time point on or after the Day 15 visit. |
| Arm/Group Title | Placebo | ARC-520 1.0 mg/kg | ARC-520 2.0 mg/kg |
|---|---|---|---|
| Arm/Group Description | Placebo (low dose or high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) |
| Measure Participants | 6 | 6 | 8 |
| No Decrease |
0.042
(NA)
|
||
| 1 participant analyDecrease > 0 to < 0.5 log IU/mL |
-0.115
(0.171)
|
-0.142
(0.045)
|
-0.359
(0.049)
|
| Decrease 0.5 to 1.0 log IU/mL |
-0.726
(0.228)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, ARC-520 1.0 mg/kg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.0000 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, ARC-520 2.0 mg/kg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0849 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | ARC-520 1.0 mg/kg, ARC-520 2.0 mg/kg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0849 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Title | Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and Discontinuations Due to AEs |
|---|---|
| Description | An AE is any untoward medical occurrence which does not necessarily have to have a causal relationship with this treatment. A treatment emergent AE (TEAE) was defined as an AE that was not present prior to the first study drug administration and started at/after the time of initiation of administration of study drug, or an AE which was present prior to initiation of study drug administration, which increased in severity after study drug administration. An SAE is any untoward medical occurrence that, at any dose: 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. |
| Time Frame | Through Day 169 (± 3 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: all participants who received at least one dose of study drug or placebo, and had at least one post-dose safety assessment. |
| Arm/Group Title | Placebo Low Dose Comparator | Placebo High Dose Comparator | ARC-520 1.0 mg/kg | ARC-520 2.0 mg/kg |
|---|---|---|---|---|
| Arm/Group Description | Placebo (low dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | Placebo (high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) |
| Measure Participants | 6 | 5 | 10 | 11 |
| ≥ 1 AE |
4
66.7%
|
0
0%
|
6
60%
|
3
27.3%
|
| ≥ 1 TEAE |
4
66.7%
|
0
0%
|
5
50%
|
3
27.3%
|
| ≥ 1 Serious TEAE |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Deaths |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| ≥ 1 TEAE Leading to Study Discontinuation |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| ≥ 1 TEAE Leading to Treatment Discontinuation |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Pharmacokinetics of ARC-520: Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24) |
|---|---|
| Description | |
| Time Frame | Through 48 hours post-dosing on Day 1 and Day 85 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to the early suspension and termination of the study, all pharmacokinetic analyses were removed from the initial statistical analysis plan for this study. No collected samples were analyzed and all were destroyed. |
| Arm/Group Title | Placebo | ARC-520 1.0 mg/kg | ARC-520 2.0 mg/kg |
|---|---|---|---|
| Arm/Group Description | Placebo (low dose or high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) |
| Measure Participants | 0 | 0 | 0 |
| Title | Pharmacokinetics of ARC-520: Area Under the Plasma Concentration-Time Curve From Time 0 to the Last Quantifiable Plasma Concentration (AUClast) |
|---|---|
| Description | |
| Time Frame | Through 48 hours post-dosing on Day 1 and Day 85 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to the early suspension and termination of the study, all pharmacokinetic analyses were removed from the initial statistical analysis plan for this study. No collected samples were analyzed and all were destroyed. |
| Arm/Group Title | Placebo | ARC-520 1.0 mg/kg | ARC-520 2.0 mg/kg |
|---|---|---|---|
| Arm/Group Description | Placebo (low dose or high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) |
| Measure Participants | 0 | 0 | 0 |
| Title | Pharmacokinetics of ARC-520: Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUCinf) |
|---|---|
| Description | |
| Time Frame | Through 48 hours post-dosing on Day 1 and Day 85 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to the early suspension and termination of the study, all pharmacokinetic analyses were removed from the initial statistical analysis plan for this study. No collected samples were analyzed and all were destroyed. |
| Arm/Group Title | Placebo High Dose Comparator | ARC-520 1.0 mg/kg | ARC-520 2.0 mg/kg |
|---|---|---|---|
| Arm/Group Description | Placebo (low dose or high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) |
| Measure Participants | 0 | 0 | 0 |
| Title | Pharmacokinetics of ARC-520: Maximum Observed Plasma Concentration (Cmax) |
|---|---|
| Description | |
| Time Frame | Through 48 hours post-dosing on Day 1 and Day 85 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to the early suspension and termination of the study, all pharmacokinetic analyses were removed from the initial statistical analysis plan for this study. No collected samples were analyzed and all were destroyed. |
| Arm/Group Title | Placebo High Dose Comparator | ARC-520 1.0 mg/kg | ARC-520 2.0 mg/kg |
|---|---|---|---|
| Arm/Group Description | Placebo (low dose or high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) |
| Measure Participants | 0 | 0 | 0 |
| Title | Pharmacokinetics of ARC-520: Clearance (CL) |
|---|---|
| Description | |
| Time Frame | Through 48 hours post-dosing on Day 1 and Day 85 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to the early suspension and termination of the study, all pharmacokinetic analyses were removed from the initial statistical analysis plan for this study. No collected samples were analyzed and all were destroyed. |
| Arm/Group Title | Placebo High Dose Comparator | ARC-520 1.0 mg/kg | ARC-520 2.0 mg/kg |
|---|---|---|---|
| Arm/Group Description | Placebo (low dose or high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) |
| Measure Participants | 0 | 0 | 0 |
| Title | Pharmacokinetics of ARC-520: Apparent Volume of Distribution (V) |
|---|---|
| Description | |
| Time Frame | Through 48 hours post-dosing on Day 1 and Day 85 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to the early suspension and termination of the study, all pharmacokinetic analyses were removed from the initial statistical analysis plan for this study. No collected samples were analyzed and all were destroyed. |
| Arm/Group Title | Placebo High Dose Comparator | ARC-520 1.0 mg/kg | ARC-520 2.0 mg/kg |
|---|---|---|---|
| Arm/Group Description | Placebo (low dose or high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) |
| Measure Participants | 0 | 0 | 0 |
| Title | Pharmacokinetics of ARC-520: Terminal Elimination Rate Constant (Kel) |
|---|---|
| Description | |
| Time Frame | Through 48 hours post-dosing on Day 1 and Day 85 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to the early suspension and termination of the study, all pharmacokinetic analyses were removed from the initial statistical analysis plan for this study. No collected samples were analyzed and all were destroyed. |
| Arm/Group Title | Placebo High Dose Comparator | ARC-520 1.0 mg/kg | ARC-520 2.0 mg/kg |
|---|---|---|---|
| Arm/Group Description | Placebo (low dose or high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) |
| Measure Participants | 0 | 0 | 0 |
| Title | Pharmacokinetics of ARC-520: Terminal Elimination Half-Life (t1/2) |
|---|---|
| Description | |
| Time Frame | Through 48 hours post-dosing on Day 1 and Day 85 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to the early suspension and termination of the study, all pharmacokinetic analyses were removed from the initial statistical analysis plan for this study. No collected samples were analyzed and all were destroyed. |
| Arm/Group Title | Placebo High Dose Comparator | ARC-520 1.0 mg/kg | ARC-520 2.0 mg/kg |
|---|---|---|---|
| Arm/Group Description | Placebo (low dose or high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) |
| Measure Participants | 0 | 0 | 0 |
Adverse Events
| Time Frame | Through Day 169 (± 3 days) | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | Placebo Low Dose Comparator | Placebo High Dose Comparator | ARC-520 1.0 mg/kg | ARC-520 2.0 mg/kg | ||||
| Arm/Group Description | Placebo (low dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | Placebo (high dose comparator) once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | Low dose (1.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | High dose (2.0 mg/kg) ARC-520 once every 4 weeks for 4 doses, plus entecavir (0.5 or 1.0 mg/day) or tenofovir (300 mg/day) | ||||
All Cause Mortality |
||||||||
| Placebo Low Dose Comparator | Placebo High Dose Comparator | ARC-520 1.0 mg/kg | ARC-520 2.0 mg/kg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Placebo Low Dose Comparator | Placebo High Dose Comparator | ARC-520 1.0 mg/kg | ARC-520 2.0 mg/kg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/6 (0%) | 0/5 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Placebo Low Dose Comparator | Placebo High Dose Comparator | ARC-520 1.0 mg/kg | ARC-520 2.0 mg/kg | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/6 (66.7%) | 0/5 (0%) | 5/10 (50%) | 3/11 (27.3%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 1/6 (16.7%) | 0/5 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Dyspepsia | 0/6 (0%) | 0/5 (0%) | 1/10 (10%) | 0/11 (0%) | ||||
| Gastrooesophageal reflux disease | 0/6 (0%) | 0/5 (0%) | 1/10 (10%) | 0/11 (0%) | ||||
| Nausea | 1/6 (16.7%) | 0/5 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| General disorders | ||||||||
| Asthenia | 0/6 (0%) | 0/5 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| Chills | 0/6 (0%) | 0/5 (0%) | 1/10 (10%) | 0/11 (0%) | ||||
| Discomfort | 0/6 (0%) | 0/5 (0%) | 1/10 (10%) | 0/11 (0%) | ||||
| Fatigue | 1/6 (16.7%) | 0/5 (0%) | 1/10 (10%) | 0/11 (0%) | ||||
| Pyrexia | 0/6 (0%) | 0/5 (0%) | 1/10 (10%) | 0/11 (0%) | ||||
| Infections and infestations | ||||||||
| Nasopharyngitis | 1/6 (16.7%) | 0/5 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| Pharyngitis | 0/6 (0%) | 0/5 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| Rhinitis | 1/6 (16.7%) | 0/5 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| Upper respiratory tract infection | 0/6 (0%) | 0/5 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| Investigations | ||||||||
| Blood creatine phosphokinase increased | 0/6 (0%) | 0/5 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| Eosinophil count increased | 0/6 (0%) | 0/5 (0%) | 0/10 (0%) | 1/11 (9.1%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthritis | 0/6 (0%) | 0/5 (0%) | 1/10 (10%) | 0/11 (0%) | ||||
| Intervertebral disc protrusion | 0/6 (0%) | 0/5 (0%) | 1/10 (10%) | 0/11 (0%) | ||||
| Nervous system disorders | ||||||||
| Dizziness | 1/6 (16.7%) | 0/5 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
| Headache | 0/6 (0%) | 0/5 (0%) | 1/10 (10%) | 0/11 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 0/6 (0%) | 0/5 (0%) | 1/10 (10%) | 0/11 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Eczema | 0/6 (0%) | 0/5 (0%) | 1/10 (10%) | 0/11 (0%) | ||||
| Urticaria | 1/6 (16.7%) | 0/5 (0%) | 0/10 (0%) | 0/11 (0%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Chief Operating Officer |
|---|---|
| Organization | Arrowhead Pharmaceuticals, Inc. |
| Phone | 626-304-3400 |
Responsible Party:
Arrowhead Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02604212
Other Study ID Numbers:
- Heparc-2003
- 2014-004751-31
First Posted:
Nov 13, 2015
Last Update Posted:
Apr 16, 2019
Last Verified:
Jan 1, 2019