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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02577029




Registration number
NCT02577029
Ethics application status
Date submitted
14/10/2015
Date registered
15/10/2015
Date last updated
12/04/2019

Titles & IDs
Public title
Study of ARC-520 With or Without Other Drugs Used in the Treatment of Chronic Chronic Hepatitis B Virus (HBV)
Scientific title
A Multicenter, Open-Label Study to Evaluate ARC-520 Administered Alone and in Combination With Other Therapeutics in Patients With Chronic Hepatitis B Virus (HBV) Infection (MONARCH)
Secondary ID [1] 0 0
2015-005499-46
Secondary ID [2] 0 0
Heparc-2008
Universal Trial Number (UTN)
Trial acronym
MONARCH
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis B 0 0
Hepatitis D 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ARC-520
Treatment: Drugs - entecavir
Other interventions - pegylated interferon alpha 2a
Treatment: Drugs - tenofovir disoproxil
Treatment: Drugs - antihistamine

Experimental: Cohort 1 - 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).

Experimental: Cohort 2 - 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.

Experimental: Cohort 3 - 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.

Experimental: Cohort 4 - 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.

Experimental: Cohort 5 - 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.

Experimental: Cohort 6 - 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.

Experimental: Cohort 7 - 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.

Experimental: Cohort 8 - 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).


Treatment: Drugs: ARC-520
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.

Treatment: Drugs: entecavir
0.5 mg once daily; oral

Other interventions: pegylated interferon alpha 2a
180 mcg; subcutaneous injection once weekly

Treatment: Drugs: tenofovir disoproxil
300 mg once daily; oral

Treatment: Drugs: antihistamine
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.

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline, Week 60
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
From first dose of study drug up to 36 weeks of treatment, plus up to 48 weeks of follow-up
Secondary outcome [2] 0 0
Percentage of Participants With HBsAg Loss (Based on Qualitative Assay) Over Time - The qualitative HBsAg assay gives a binary result, positive or negative.
Timepoint [2] 0 0
Weeks 52, 60, 72 and 96
Secondary outcome [3] 0 0
Percentage of Participants Achieving a 1-log Reduction in HBsAg and Achieving an HBsAg Level < 100 IU/L Over Time
Timepoint [3] 0 0
Weeks 52, 60, 72 and 96
Secondary outcome [4] 0 0
Time to HBsAg Loss
Timepoint [4] 0 0
Baseline through Week 96
Secondary outcome [5] 0 0
Time to Anti-HBs (Antibody to Hepatitis B Surface Antigen) Seroconversion
Timepoint [5] 0 0
Baseline through Week 96
Secondary outcome [6] 0 0
Percentage of Participants With Anti-HBs Seroconversion Over Time
Timepoint [6] 0 0
Weeks 52, 60, 72 and 96
Secondary outcome [7] 0 0
Percentage of Participants With HBeAg Loss and Anti-Hepatitis B e Antigen (Anti-HBe) Seroconversion (if HBeAg-Positive at Study Entry) Over Time
Timepoint [7] 0 0
Weeks 52, 60, 72 and 96
Secondary outcome [8] 0 0
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.
Timepoint [8] 0 0
Week 52
Secondary outcome [9] 0 0
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.
Timepoint [9] 0 0
Baseline, Week 60
Secondary outcome [10] 0 0
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)
Timepoint [10] 0 0
Weeks 52, 60, 72 and 96
Secondary outcome [11] 0 0
Log Change From Baseline in Quantitative HBV Deoxyribonucleic Acid (DNA) Serum Levels Over Time
Timepoint [11] 0 0
Baseline, Weeks 52, 60, 72 and 96

Eligibility
Key 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

- Diagnosis of HBeAg negative or positive chronic HBV infection.

- Must be HBsAg (+) during screening.

- Must be treatment naïve: never on PEG IFN alpha 2a and/or ETV or TDF; and

- Have not used nucleoside/nucleotide analogs (NUCs) within the last 2 years prior to
dosing on Day 1

- Must use 2 effective methods of contraception (double barrier contraception or
hormonal contraceptive along with a barrier contraceptive) (both male and female
partners)
Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Pregnant or lactating

- Acute signs of hepatitis/other severe infections within 4 weeks of screening

- Use within the last 14 days or anticipated requirement for anticoagulants, systemic
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, over-the-counter (OTC) and prescription pain medication or
hormonal contraceptives

- History of poorly controlled autoimmune disease or any history of autoimmune hepatitis

- History of heterozygous or homozygous familial hypercholesterolemia.

- Human immunodeficiency virus (HIV) infection

- Is sero-positive for Hepatitis C Virus (HCV), or has a history of delta virus
hepatitis (except for cohort in which delta virus infection is acceptable)

- Has hypertension: blood pressure > 170/100 mmHg; well-controlled blood pressure on
hypertensive medication allowed

- History of cardiac rhythm disturbances

- Family history of 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 major surgery within 1 month of screening

- Regular use of alcohol within 6 months prior to screening (ie, more than 14 units of
alcohol per week)

- Use of recreational drugs such as cocaine, phencyclidine (PCP), and methamphetamines,
within 1 year prior to the screening

- History of allergy to bee sting

- Clinically significant history of any alcoholic liver disease, cirrhosis, Wilson's
disease, hemochromatosis, or alpha-1 antitrypsin deficiency

- Presence of cholangitis, cholecystitis, cholestasis, or duct obstruction

- Clinically significant history or presence of poorly controlled/uncontrolled systemic
disease

- Presence of any medical or psychiatric condition or social situation that impacts
compliance or results in additional safety risk

- History of coagulopathy/stroke within past 6 months, and/or concurrent anticoagulant
medication(s)

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC,WA
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Concord Repatriation General Hospital, Gastroenterology & Liver Services - Concord
Recruitment hospital [3] 0 0
St. Vincent's Hospital Sydney - Darlinghurst
Recruitment hospital [4] 0 0
Westmead Hospital - Westmead
Recruitment hospital [5] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [6] 0 0
Monash Health Clayton Campus - Clayton
Recruitment hospital [7] 0 0
St. Vincent's Hospital Melbourne - Fitzroy
Recruitment hospital [8] 0 0
Royal Melbourne Hospital - Parkville
Recruitment hospital [9] 0 0
Linear Clinical Research Ltd. - Nedlands
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2139 - Concord
Recruitment postcode(s) [3] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [4] 0 0
2145 - Westmead
Recruitment postcode(s) [5] 0 0
5000 - Adelaide
Recruitment postcode(s) [6] 0 0
3168 - Clayton
Recruitment postcode(s) [7] 0 0
3065 - Fitzroy
Recruitment postcode(s) [8] 0 0
3052 - Parkville
Recruitment postcode(s) [9] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
Bulgaria
State/province [1] 0 0
Pleven
Country [2] 0 0
Bulgaria
State/province [2] 0 0
Sofia
Country [3] 0 0
Bulgaria
State/province [3] 0 0
Varna
Country [4] 0 0
China
State/province [4] 0 0
Hong Kong
Country [5] 0 0
Korea, Republic of
State/province [5] 0 0
Busan
Country [6] 0 0
Korea, Republic of
State/province [6] 0 0
Daegu
Country [7] 0 0
Korea, Republic of
State/province [7] 0 0
Seoul
Country [8] 0 0
Moldova, Republic of
State/province [8] 0 0
Chisinau
Country [9] 0 0
New Zealand
State/province [9] 0 0
Aukland
Country [10] 0 0
New Zealand
State/province [10] 0 0
Otago-Southland
Country [11] 0 0
New Zealand
State/province [11] 0 0
Auckland
Country [12] 0 0
Taiwan
State/province [12] 0 0
Yunlin County
Country [13] 0 0
Taiwan
State/province [13] 0 0
Changhua
Country [14] 0 0
Taiwan
State/province [14] 0 0
Kaohsiung
Country [15] 0 0
Thailand
State/province [15] 0 0
Bangkok
Country [16] 0 0
Thailand
State/province [16] 0 0
Chiang Mai
Country [17] 0 0
Thailand
State/province [17] 0 0
Khon Kaen
Country [18] 0 0
Thailand
State/province [18] 0 0
Pathumthani

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Arrowhead Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02577029
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02577029