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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/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
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
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
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
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
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
Sex
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
1/12/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/12/2016
Sample size
Target
Accrual to date
Final
79
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/ct2/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/ct2/show/NCT02577029