A Multicenter, Open-label, Randomized Clinical Study to Assess Efficacy and Safety of 3 Doses of Myrcludex B for 24 Weeks in Combination With Tenofovir Compared to Tenofovir Alone to Suppress HBV Replication in Patients With Chronic Hepatitis D

• Sponsor: Hepatera Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03546621
• Collaborator: Data Matrix Solutions (Other)
• Enrollment: 120
• Locations: 15
• Arms: 4
• Actual Duration (Months): 23.5
• Patients Per Site: 8
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This is a multicenter, open-label, randomized clinical trial to Assess Efficacy and Safety of 3 Doses of Myrcludex B for 24 Weeks in Combination with Tenofovir Compared to Tenofovir Alone to Suppress HBV Replication in Patients with Chronic Hepatitis D

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis D Infection With Hepatitis B	Drug: Myrcludex B; Drug: Myrcludex-B; Drug: Myrcludex-B; Drug: Tenofovir	Phase 2

Detailed Description

This is a multicenter, open-label, randomised, phase II study.

The study will be conducted in Russia and Germany. The study is designed to evaluate the benefit of 3 MXB doses versus observation in patients on background therapy with tenofovir, suffering from hepatitis delta with very limited therapeutic options; the patients will be randomized 1:1:1:1 into 3 treatment arms and an observation arm. Patients with compensated cirrhosis at screening will be stratified to allow similar distribution into each treatment arm. If patients were not receiving treatment with nucleoside/nucelotide analogue, the comparator/background drug will be initiated after the eligibility confirmation, for 12 weeks prior to randomization visit; patients who previously received tenofovir will continue the dosing; patients on different nucleoside/nucleotide analogue will be switched to tenofovir. Observation is considered an adequate control group, as daily placebo injections for 24 weeks are regarded not feasible and ethically questionable.

It is planned to screen 200 patients, and 120 patients will be randomised into four treatment arms in the 1:1:1:1 ratio.

• Arm A (30 patients): Myrcludex B, 2 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy.

• Arm B (30 patients): Myrcludex B, 5 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy.

• Arm C (30 patients): Myrcludex B, 10 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy.

• Arm D (30 patients): tenofovir treatment for 48 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Multicenter, Open-label, RandomizedMulticenter, Open-label, Randomized
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Open-label, Randomized Clinical Study to Assess Efficacy and Safety of 3 Doses of Myrcludex B for 24 Weeks in Combination With Tenofovir Compared to Tenofovir Alone to Suppress HBV Replication in Patients With Chronic Hepatitis D
• Actual Study Start Date: Feb 16, 2016
• Actual Primary Completion Date: Jan 31, 2018
• Actual Study Completion Date: Jan 31, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A Myrcludex B, 2 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy.	Drug: Myrcludex B; 2 mg, once daily, subcutaneously; Drug: Tenofovir; tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg; Other Names: Viread
Experimental: Arm B Myrcludex B, 5 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy.	Drug: Myrcludex-B; 5 mg, once daily, subcutaneously; Drug: Tenofovir; tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg; Other Names: Viread
Experimental: Arm C Myrcludex B, 10 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy.	Drug: Myrcludex-B; 10 mg, once daily, subcutaneously; Drug: Tenofovir; tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg; Other Names: Viread
Active Comparator: Arm D tenofovir treatment for 48 weeks	Drug: Tenofovir; tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg; Other Names: Viread

Outcome Measures

Primary Outcome Measures

1. HDV RNA Response at Week 24 [24 weeks]

   HDV RNA negativation or decrease by ≥2 log10 from baseline to Week 24

Secondary Outcome Measures

1. Durability of HDV RNA Response [48 weeks]

   Durability of HDV RNA response to 24 weeks post treatment

2. Combined Response: HDV RNA Response and Normal ALT at Treatment Week 24 [24 weeks]

   Combined response: HDV RNA negativation or ≥2 log decline and normal ALT at treatment week 24

3. Changes in ALT Values [24 and 48 weeks]

   Changes in ALT values at Week 24 and Week 48 compared to baseline.

4. Change (Absence of Increase) in Fibrosis Marker [24 and 48 weeks]

   Change (absence of increase) in fibrosis marker: serum alpha-2-macroglobulin at Week 24 and Week 48 compared to baseline

5. Change in Hepatitis B Surface Antigen [24 and 48 weeks]

   Changes in hepatitis B surface antigen (HBsAg) (defined as decline in HBsAg levels, disappearance of HBsAg and HBsAg seroconversion to anti-HBsAg) at week 24 and week 48 compared to baseline

6. Change in HBV DNA Levels at Week 24 and Week 48 Compared to Baseline [24 and 48 weeks]

   Change in hepatitis B virus (HBV) DNA levels at Week 24 and Week 48 compared to baseline.

7. Absence of a Fibrosis Progression According to the Findings of Transient Elastometry [24 weeks]

   Decrease in liver stiffness and absence of a fibrosis progression according to the findings of transient elastometry (fibroscan) at week 24 compared to baseline

8. Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results [24 weeks]

   Change (improvement/ worsening) in fibrosis and histological activity stage according to the liver biopsy study results at week 24 compared to baseline. Liver fibrosis was evaluated by histological staging systems with stage 0 corresponding to absence of fibrosis and with the highest score (the last stage in all systems) corresponding to cirrhosis. Improvement is defined as a decrease of at least 1 point in histological staging systems; worsening is defined as an increase of at least 1 point. Data should be interpreted with caution due to low number of paired biopsies available.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Age from 18 to 65 years inclusively at the time of signing Informed Consent Form.

2. Positive serum HBsAg for at least 6 months before Screening.

3. Positive serum anti-HDV antibody for at least 6 months before screening.

4. Positive PCR results for serum HDV RNA at Screening.

5. Patients with liver cirrhosis, irrespective of previous interferon treatment .

6. Patients without liver cirrhosis, who failed prior interferon treatment or for whom, in the opinion of the Investigator, such treatment is currently contraindicated (including history of interferon intolerance) .

7. Alanine aminotransferase level >1 x ULN, but less than 10 x ULN.

8. Previous nucleotide/nucleoside analogue treatment within at least 12 weeks prior to the planned start of study treatment or subject's willingness to take tenofovir for at least 12 weeks prior to the planned start of study treatment.

9. Negative urine pregnancy test for females of childbearing potential.

10. Inclusion criteria for female subjects:

• Postmenopausal for at least 2 years, or

• Surgically sterile (total hysterectomy or bilateral oophorectomy, bilateral tubal ligation, staples, or another type of sterilization), or

• Abstinence from heterosexual intercourse throughout the study, or

• Willingness to use highly effective contraception throughout the study and for 3 months after the last dose of the study medication.

1. Male and female subjects must agree to use a highly effective contraception throughout the study and for 3 months after the last dose of the study medication.

2. Male subjects must agree not to donate sperm throughout the study and for 3 months after the last dose of the study medication.

Exclusion Criteria:

1. Child-Pugh score of B-C or over 6 points.

2. HCV or HIV coinfection. Subjects with anti-HCV antibodies can be enrolled, if screening HCV RNA test is negative.

3. Creatinine clearance <60 mL/min.

4. Total bilirubin ≥ 2mg/dL. Patients with higher total bilirubin values may be included after the consultation with the Study's Medical Monitor, if such elevation can be clearly attributed to Gilbert's syndrome associated with low-grade hyperbilirubinemia.

5. Any previous or current malignant neoplasms, including hepatic carcinoma.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ifi-Institut für interdisziplinäre Medizin an der Asklepios Klinik St. Georg	Hamburg		Germany
2	Universitätsklinikum Hamburg-Eppendorf Medizinische Klinik Studienambulanz Hepatologie	Hamburg		Germany
3	Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover	Hannover		Germany
4	UniversitätsKlinikum Heidelberg - Medizinische Klinik, Abteilung Klinische Pharmakologie & Pharmakoepidemiologie	Heidelberg		Germany
5	State Budgetary educational institution of higher professional education "South Ural State Medical University" Ministry of healthcare	Chelyabinsk		Russian Federation
6	State Autonomous Healthcare Institution "Republican Clinical Infectious Diseases Hospital named after Prof. A.F. Agafonov "(SAHI RCID)	Kazan		Russian Federation
7	Federal Budget Institution of Science "Central Research Institute of Epidemiology" of The Federal Service on Customers' Rights Protection and Human Well-being Surveillance	Moscow		Russian Federation
8	LLC "Clinic of Modern Medicine"	Moscow		Russian Federation
9	Moscow Regional Research Clinical Institute n.a. M.F. Vladimirskiy	Moscow		Russian Federation
10	State Budget Health Institution of Moscow "Infectious Clinical Hospital No. 1 of the Moscow Healthcare Department"	Moscow		Russian Federation
11	State Budgetary Healthcare Institution "Moscow Clinical Scientific and Practical Center of the Department of Public Health of Moscow"	Moscow		Russian Federation
12	State Budgetary Educational Institution of Higher Professional Education "Novosibirsk State Medical University" of the Ministry of Health of the Russian Federation	Novosibirsk		Russian Federation
13	Medical Company "Hepatolog"	Samara		Russian Federation
14	Stavropol Regional Clinical Hospital	Stavropol'		Russian Federation
15	State Budgetary institution of the Republic of Sakha (Yakutia) "Yakutsk Clinical Hospital"	Yakutsk		Russian Federation

Sponsors and Collaborators

• Hepatera Ltd.
• Data Matrix Solutions

Investigators

• Principal Investigator: Heiner Wedemeyer, MD,PhD, Dept. of Gastroenterology, Hepatology and Endocrinology Medizinische Hochschule Hannover

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form: Protocol_v.7.0_28.09.2017_Russia + SAP + ICF - Sep 28, 2017
• Study Protocol: Protocol_v.3.0_25.12.2107_Germany - Dec 25, 2017

More Information

Publications

None provided.

• Responsible Party: Hepatera Ltd.
• ClinicalTrials.gov Identifier: NCT03546621
• Other Study ID Numbers: MYR 202
• First Posted: Jun 6, 2018
• Last Update Posted: May 10, 2021
• Last Verified: Apr 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Hepatera Ltd.: Hepatitis D
• Additional relevant MeSH terms: Hepatitis A; Hepatitis B; Hepatitis D; Hepatitis D, Chronic; Hepatitis; Hepatitis, Chronic; Tenofovir

Study Results

Participant Flow

Recruitment Details	Of 120 randomized patients 118 started treatment with study medication (2 patients from Tenofovir only group withdrew before treatment)

Arm/Group Title	Arm A	Arm B	Arm C	Arm D
Arm/Group Description	Myrcludex B, 2 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Myrcludex B: 2 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	Myrcludex B, 5 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Myrcludex-B: 5 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	Myrcludex B, 10 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Myrcludex-B: 10 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	tenofovir treatment for 48 weeks Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
Period Title: Overall Study
STARTED	28	32	30	28
COMPLETED	28	29	28	25
NOT COMPLETED	0	3	2	3

Baseline Characteristics

Arm/Group Title	Arm A	Arm B	Arm C	Arm D	Total
Arm/Group Description	Myrcludex B, 2 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Myrcludex B: 2 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	Myrcludex B, 5 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Myrcludex-B: 5 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	Myrcludex B, 10 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Myrcludex-B: 10 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	tenofovir treatment for 48 weeks Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	Total of all reporting groups
Overall Participants	28	32	30	28	118
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	28 100%	32 100%	30 100%	28 100%	118 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.4 (8.3)	40.9 (9.5)	41.8 (11.3)	38.5 (8.7)	40.2 (9.5)
Sex: Female, Male (Count of Participants)
Female	13 46.4%	11 34.4%	7 23.3%	8 28.6%	39 33.1%
Male	15 53.6%	21 65.6%	23 76.7%	20 71.4%	79 66.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	7 25%	1 3.1%	3 10%	5 17.9%	16 13.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	1 3.1%	0 0%	0 0%	1 0.8%
White	21 75%	30 93.8%	27 90%	23 82.1%	101 85.6%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Height (cm) (cm.) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm.]	168.5 (8.3)	172.9 (7.4)	173.8 (9.8)	172.8 (9.4)	172.0 (8.9)
Body Weight (kg) (kg.) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg.]	70.19 (13.54)	75.09 (12.54)	77.59 (13.72)	79.15 (17.21)	75.53 (14.49)
Body Mass Index (kg/m²) (participants) [Number]
<30 kg/m²	27 96.4%	31 96.9%	28 93.3%	22 78.6%	108 91.5%
≥30 kg/m²	1 3.6%	1 3.1%	2 6.7%	6 21.4%	10 8.5%

Outcome Measures

1. Primary Outcome

Title	HDV RNA Response at Week 24
Description	HDV RNA negativation or decrease by ≥2 log10 from baseline to Week 24
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Arm A	Arm B	Arm C	Arm D
Arm/Group Description	Myrcludex B, 2 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Myrcludex B: 2 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	Myrcludex B, 5 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Myrcludex-B: 5 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	Myrcludex B, 10 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Myrcludex-B: 10 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	tenofovir treatment for 48 weeks Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
Measure Participants	28	32	30	28
Responder	15 53.6%	16 50%	23 76.7%	1 3.6%
Non-Responder	13 46.4%	16 50%	7 23.3%	27 96.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A, Arm B, Arm C
	Comments	For each of the three Myrcludex B treatment groups, a null hypothesis of no clinically significant difference in proportion of responders compared to the control group (Tenofovir only), at week 24, were tested using the one-sided Wald test for superiority, at a one-sided overall significance level of 0.05 adjusted for multiple testing according to Bonferroni-Holm, with the superiority limit (test margin) set to 5%.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Bonferroni-Holm
	Comments

2. Secondary Outcome

Title	Durability of HDV RNA Response
Description	Durability of HDV RNA response to 24 weeks post treatment
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Arm A	Arm B	Arm C	Arm D
Arm/Group Description	Myrcludex B, 2 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Myrcludex B: 2 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	Myrcludex B, 5 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Myrcludex-B: 5 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	Myrcludex B, 10 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Myrcludex-B: 10 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	tenofovir treatment for 48 weeks Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
Measure Participants	28	32	30	28
Response at Week 24 only	15 53.6%	16 50%	23 76.7%	1 3.6%
Response at Week 24 and 48	2 7.1%	1 3.1%	3 10%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A, Arm D
	Comments	Week 48. Two-sided Fisher's exact tests were used to test null hypothesis of no difference in the proportion of responders compared to the Tenofovir only group. Separate comparisons were made for each of the three Myrcludex B groups versus the control group, and the adjusted p-values were computed using the Bonferroni-Holm method.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9818
	Comments	A test is considered as statistically significant if the adjusted p-value is smaller than 0.05.
	Method	Bonferroni-Holm
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm B, Arm D
	Comments	Week 48. Two-sided Fisher's exact tests were used to test null hypothesis of no difference in the proportion of responders compared to the Tenofovir only group. Separate comparisons were made for each of the three Myrcludex B groups versus the control group, and the adjusted p-values were computed using the Bonferroni-Holm method.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments	A test is considered as statistically significant if the adjusted p-value as smaller than 0.05
	Method	Bonferroni-Holm
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Arm C, Arm D
	Comments	Week 48. Two-sided Fisher's exact tests were used to test null hypothesis of no difference in the proportion of responders compared to the Tenofovir only group. Separate comparisons were made for each of the three Myrcludex B groups versus the control group, and the adjusted p-values were computed using the Bonferroni-Holm method.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7132
	Comments	The threshold for statistical significance was p=0.05
	Method	Bonferroni-Holm
	Comments

3. Secondary Outcome

Title	Combined Response: HDV RNA Response and Normal ALT at Treatment Week 24
Description	Combined response: HDV RNA negativation or ≥2 log decline and normal ALT at treatment week 24
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Arm A	Arm B	Arm C	Arm D
Arm/Group Description	Myrcludex B, 2 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Myrcludex B: 2 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	Myrcludex B, 5 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Myrcludex-B: 5 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	Myrcludex B, 10 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Myrcludex-B: 10 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	tenofovir treatment for 48 weeks Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
Measure Participants	28	32	30	28
Responder	6 21.4%	9 28.1%	11 36.7%	0 0%
Non-Responder	22 78.6%	23 71.9%	19 63.3%	28 100%
Responder	2 7.1%	1 3.1%	1 3.3%	0 0%
Non-Responder	26 92.9%	31 96.9%	29 96.7%	28 100%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A, Arm D
	Comments	Fisher's exact test was used to test a null hypothesis of no difference in proportions against a two-sided alternative hypothesis. Separate tests were performed for each of the three Myrcludex B treatment groups against the control group, at week 24 and week 48, and adjusted p-values were computered using the Bonferroni-Holm method. This analysis, and presentation of descriptive statistics, was repeated for the subgroups of patients with normal/abnormal baseline ALT values.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0232
	Comments	A test is considered as statistically significant if the adjusted p-value is smaller than 0.05.
	Method	Bonferroni-Holm
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm B, Arm D
	Comments	Fisher's exact test was used to test a null hypothesis of no difference in proportions against a two-sided alternative hypothesis. Separate tests were performed for each of the three Myrcludex B treatment groups against the control group, at week 24 and week 48, and adjusted p-values were computered using the Bonferroni-Holm method.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0047
	Comments	The threshold for statistical significance was p=0.05
	Method	Bonferroni-Holm
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Arm C, Arm D
	Comments	Fisher's exact test was used to test a null hypothesis of no difference in proportions against a two-sided alternative hypothesis. Separate tests were performed for each of the three Myrcludex B treatment groups against the control group, at week 24 and week 48, and adjusted p-values were computered using the Bonferroni-Holm method.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0010
	Comments	The threshold for statistical significance was p=0.05
	Method	Bonferroni-Holm
	Comments

4. Secondary Outcome

Title	Changes in ALT Values
Description	Changes in ALT values at Week 24 and Week 48 compared to baseline.
Time Frame	24 and 48 weeks

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Arm A	Arm B	Arm C	Arm D
Arm/Group Description	Myrcludex B, 2 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Myrcludex B: 2 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	Myrcludex B, 5 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Myrcludex-B: 5 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	Myrcludex B, 10 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Myrcludex-B: 10 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	tenofovir treatment for 48 weeks Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
Measure Participants	28	32	30	28
Change from Baseline to Week 24	-49.6 (58.7)	-79.4 (84.2)	-78.9 (81.1)	-29.2 (61.4)
Change from Baseline to Week 48	-1.6 (72.8)	-18.2 (94.4)	1.4 (76.0)	-26.3 (39.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A, Arm D
	Comments	Week 24. The change from baseline to week 24 and week 48 in ALT levels was performed using van Elteren tests. Fisher's exact test was used to test a null hypothesis of no difference in proportions (of patients with normal ALT values) against a two-sided alternative hypothesis. Separate tests were performed for each of the three Myrcludex B treatment groups against the control group, at week 24 and week 48, and adjusted p-values were computed using the Bonferroni-Holm method.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1642
	Comments	A test is considered as statistically significant if the adjusted p-value is smaller than 0.05.
	Method	Bonferroni-Holm
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm B, Arm D
	Comments	Week 24
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0428
	Comments	A test is considered statistically significant if the adjusted p-value is smaller than 0.05
	Method	Bonferroni-Holm
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Arm C, Arm D
	Comments	Week 24
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0428
	Comments	A test is considered statistically significant if the adjusted p-value is smaller than 0.05
	Method	Bonferroni-Holm
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Arm A, Arm D
	Comments	Week 48
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2388
	Comments	A test is considered as statistically significant if the adjusted p-value is smaller than 0.05.
	Method	Boferroni-Holm
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Arm B, Arm D
	Comments	Week 48
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7157
	Comments	A test is considered as statistically significant if the adjusted p-value is smaller than 0.05.
	Method	Bonferroni-Holm
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Arm C, Arm D
	Comments	Week 48
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2388
	Comments	A test is considered as statistically significant if the adjusted p-value is smaller than 0.05.
	Method	Bonferroni-Holm
	Comments

5. Secondary Outcome

Title	Change (Absence of Increase) in Fibrosis Marker
Description	Change (absence of increase) in fibrosis marker: serum alpha-2-macroglobulin at Week 24 and Week 48 compared to baseline
Time Frame	24 and 48 weeks

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Arm A	Arm B	Arm C	Arm D
Arm/Group Description	Myrcludex B, 2 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Myrcludex B: 2 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	Myrcludex B, 5 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Myrcludex-B: 5 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	Myrcludex B, 10 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Myrcludex-B: 10 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	tenofovir treatment for 48 weeks Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
Measure Participants	28	32	30	28
Change from Baseline to Week 24	-0.076 (0.320)	0.020 (0.280)	0.024 (0.257)	-0.141 (0.607)
Change from Baseline to Week 48	-0.056 (0.416)	0.075 (0.360)	-0.008 (0.265)	-0.031 (0.485)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A, Arm D
	Comments	Week 24. Two-sided van Elteren tests, stratified by presence of cirrhosis, were used to test for differences compared to the control group. Separate comparisons were made for each of the three MXB groups versus the control group, and adjusted p-values were computed using the Bonferroni-Holm method.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7416
	Comments	A test is considered as statistically significant if the adjusted p-value is smaller than 0.05.
	Method	Bonferroni-Holm
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm B, Arm D
	Comments	Week 24
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4434
	Comments	A test is considered as statistically significant if the adjusted p-value is smaller than 0.05.
	Method	Bonferroni-Holm
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Arm C, Arm D
	Comments	Week 24.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7371
	Comments	A test is considered as statistically significant if the adjusted p-value is smaller than 0.05.
	Method	Bonferroni-Holm
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Arm A, Arm D
	Comments	Week 48
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments	A test is considered as statistically significant if the adjusted p-value is smaller than 0.05.
	Method	Bonferroni-Holm
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Arm B, Arm D
	Comments	Week 48
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9441
	Comments	A test is considered as statistically significant if the adjusted p-value is smaller than 0.05.
	Method	Bonferroni-Holm
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Arm C, Arm D
	Comments	Week 48
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments	A test is considered as statistically significant if the adjusted p-value is smaller than 0.05.
	Method	Bonferroni-Holm
	Comments

6. Secondary Outcome

Title	Change in Hepatitis B Surface Antigen
Description	Changes in hepatitis B surface antigen (HBsAg) (defined as decline in HBsAg levels, disappearance of HBsAg and HBsAg seroconversion to anti-HBsAg) at week 24 and week 48 compared to baseline
Time Frame	24 and 48 weeks

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Arm A	Arm B	Arm C	Arm D
Arm/Group Description	Myrcludex B, 2 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Myrcludex B: 2 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	Myrcludex B, 5 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Myrcludex-B: 5 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	Myrcludex B, 10 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Myrcludex-B: 10 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	tenofovir treatment for 48 weeks Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
Measure Participants	28	32	30	28
Change from Baseline to Week 24	-0.048 (0.392)	0.003 (0.175)	0.034 (0.106)	0.025 (0.239)
Change from Baseline to Week 48	-0.138 (0.288)	-0.162 (0.412)	-0.134 (0.175)	-0.070 (0.186)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A, Arm D
	Comments	Week 24. The change from baseline to Week 24 in HBsAg was performed using van Elteren tests. Tests were performed on log-10 transformed data. Separare comparisons were made for each of the three Myrcludex B groups versus the control group, and the adjusted values were computed using the Bonferroni-Holm method.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5984
	Comments	A test is considered as statistically significant if the adjusted p-value is smaller than 0.05.
	Method	Bonferroni-Holm
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm B, Arm D
	Comments	Week 24
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7529
	Comments	A test is considered as statistically significant if the adjusted p-value is smaller than 0.05.
	Method	Bonferroni-Holm
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Arm C, Arm D
	Comments	Week 24
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3305
	Comments	A test is considered as statistically significant if the adjusted p-value is smaller than 0.05.
	Method	Bonferroni-Holm
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Arm A, Arm D
	Comments	Week 48
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments	A test is considered as statistically significant if the adjusted p-value is smaller than 0.05.
	Method	Bonferroni-Holm
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Arm B, Arm D
	Comments	Week 48
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments	A test is considered as statistically significant if the adjusted p-value is smaller than 0.05.
	Method	Bonferroni-Holm
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Arm C, Arm D
	Comments	Week 48
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments	A test is considered as statistically significant if the adjusted p-value is smaller than 0.05.
	Method	Bonferroni-Holm
	Comments

7. Secondary Outcome

Title	Change in HBV DNA Levels at Week 24 and Week 48 Compared to Baseline
Description	Change in hepatitis B virus (HBV) DNA levels at Week 24 and Week 48 compared to baseline.
Time Frame	24 and 48 weeks

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Arm A	Arm B	Arm C	Arm D
Arm/Group Description	Myrcludex B, 2 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Myrcludex B: 2 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	Myrcludex B, 5 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Myrcludex-B: 5 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	Myrcludex B, 10 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Myrcludex-B: 10 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	tenofovir treatment for 48 weeks Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
Measure Participants	28	32	30	28
Change from Baseline to Week 24	-0.314 (0.956)	-0.484 (1.106)	-0.173 (1.144)	-0.343 (1.151)
Change from Baseline to Week 48	-0.244 (0.828)	-0.194 (1.416)	-0.267 (1.275)	-0.257 (0.979)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm A, Arm D
	Comments	Week 24. Two-sided van Elteren tests, stratified by presence of cirrhosis, were used to test for differences compared to the control group. Tests were performed on log-10 transformed data. Separate comparisons were made for each of the three MXB groups versus the control group, and adjusted p-values were computed using the Bonferroni-Holm method.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments	A test is considered as statistically significant if the adjusted p-value is smaller than 0.05.
	Method	Bonferroni-Holm
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arm B, Arm D
	Comments	Week 24.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments
	Method	Bonferroni-Holm
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Arm C, Arm D
	Comments	Week 24
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments
	Method	Bonferroni-Holm
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Arm A, Arm D
	Comments	Week 48
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments	A test is considered as statistically significant if the adjusted p-value is smaller than 0.05
	Method	Bonferroni-Holm
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Arm B, Arm D
	Comments	Week 48
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments	A test is considered as statistically significant if the adjusted p-value is smaller than 0.05.
	Method	Bonferroni-Holm
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Arm C, Arm D
	Comments	Week 48
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments	A test is considered as statistically significant if the adjusted p-value is smaller than 0.05.
	Method	Bonferroni-Holm
	Comments

8. Secondary Outcome

Title	Absence of a Fibrosis Progression According to the Findings of Transient Elastometry
Description	Decrease in liver stiffness and absence of a fibrosis progression according to the findings of transient elastometry (fibroscan) at week 24 compared to baseline
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Arm A	Arm B	Arm C	Arm D
Arm/Group Description	Myrcludex B, 2 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Myrcludex B: 2 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	Myrcludex B, 5 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Myrcludex-B: 5 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	Myrcludex B, 10 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Myrcludex-B: 10 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	tenofovir treatment for 48 weeks Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
Measure Participants	28	32	30	28
Baseline	14.45 (6.37)	17.18 (11.49)	16.00 (7.37)	16.20 (7.83)
Change from Baseline to Week 24	-2.85 (2.65)	-2.52 (6.21)	-3.38 (3.83)	-0.78 (3.17)

9. Secondary Outcome

Title	Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results
Description	Change (improvement/ worsening) in fibrosis and histological activity stage according to the liver biopsy study results at week 24 compared to baseline. Liver fibrosis was evaluated by histological staging systems with stage 0 corresponding to absence of fibrosis and with the highest score (the last stage in all systems) corresponding to cirrhosis. Improvement is defined as a decrease of at least 1 point in histological staging systems; worsening is defined as an increase of at least 1 point. Data should be interpreted with caution due to low number of paired biopsies available.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	Arm A	Arm B	Arm C	Arm D
Arm/Group Description	Myrcludex B, 2 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Myrcludex B: 2 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	Myrcludex B, 5 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Myrcludex-B: 5 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	Myrcludex B, 10 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Myrcludex-B: 10 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	tenofovir treatment for 48 weeks Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
Measure Participants	7	5	7	4
Improvement	1 3.6%	1 3.1%	3 10%	1 3.6%
No change	3 10.7%	1 3.1%	2 6.7%	1 3.6%
Worsening	3 10.7%	3 9.4%	2 6.7%	2 7.1%
Improvement	1 3.6%	1 3.1%	3 10%	2 7.1%
No change	2 7.1%	2 6.3%	2 6.7%	0 0%
Worsening	4 14.3%	2 6.3%	2 6.7%	2 7.1%
Improvement	2 7.1%	1 3.1%	3 10%	1 3.6%
No change	1 3.6%	2 6.3%	4 13.3%	2 7.1%
Worsening	4 14.3%	2 6.3%	0 0%	1 3.6%
Improvement	2 7.1%	2 6.3%	3 10%	3 10.7%
No change	4 14.3%	1 3.1%	3 10%	0 0%
Worsening	1 3.6%	2 6.3%	1 3.3%	1 3.6%
Improvement	4 14.3%	2 6.3%	3 10%	3 10.7%
No change	0 0%	1 3.1%	1 3.3%	0 0%
Worsening	3 10.7%	2 6.3%	3 10%	1 3.6%

Adverse Events

Time Frame	48 weeks
Arm/Group Title	Arm A		Arm B		Arm C		Arm D
Arm/Group Description	Myrcludex B, 2 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Myrcludex B: 2 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg		Myrcludex B, 5 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Myrcludex-B: 5 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg		Myrcludex B, 10 mg/day subcutaneously (s.c.) for 24 weeks + tenofovir with a further follow-up period of 24 weeks of continued tenofovir therapy. Myrcludex-B: 10 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg		tenofovir treatment for 48 weeks Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
All Cause Mortality
	Arm A		Arm B		Arm C		Arm D
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/28 (0%)		0/32 (0%)		0/30 (0%)		0/28 (0%)
Serious Adverse Events
	Arm A		Arm B		Arm C		Arm D
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/28 (0%)		3/32 (9.4%)		2/30 (6.7%)		1/28 (3.6%)
Blood and lymphatic system disorders
Anaemia	0/28 (0%)	0	1/32 (3.1%)	1	0/30 (0%)	0	0/28 (0%)	0
Hepatobiliary disorders
Hepatic cirrhosis	0/28 (0%)	0	0/32 (0%)	0	0/30 (0%)	0	1/28 (3.6%)	1
Cholecystitis	0/28 (0%)	0	0/32 (0%)	0	1/30 (3.3%)	1	0/28 (0%)	0
Investigations
ALT increased	0/28 (0%)	0	2/32 (6.3%)	2	0/30 (0%)	0	0/28 (0%)	0
Renal and urinary disorders
Renal colic	0/28 (0%)	0	0/32 (0%)	0	1/30 (3.3%)	1	0/28 (0%)	0
Other (Not Including Serious) Adverse Events
	Arm A		Arm B		Arm C		Arm D
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/28 (64.3%)		19/32 (59.4%)		21/30 (70%)		13/28 (46.4%)
Blood and lymphatic system disorders
Thrombocytopenia	3/28 (10.7%)	3	5/32 (15.6%)	10	2/30 (6.7%)	5	3/28 (10.7%)	4
Neutropenia	1/28 (3.6%)	1	4/32 (12.5%)	8	0/30 (0%)	0	3/28 (10.7%)	4
Leukopenia	4/28 (14.3%)	4	2/32 (6.3%)	4	0/30 (0%)	0	1/28 (3.6%)	1
Lymphopenia	3/28 (10.7%)	3	0/32 (0%)	0	0/30 (0%)	0	0/28 (0%)	0
Anaemia	1/28 (3.6%)	1	1/32 (3.1%)	4	1/30 (3.3%)	1	0/28 (0%)	0
Lymphocytosis	0/28 (0%)	0	2/32 (6.3%)	2	0/30 (0%)	0	2/28 (7.1%)	2
Eosiniphilia	0/28 (0%)	0	0/32 (0%)	0	1/30 (3.3%)	1	0/28 (0%)	0
Lymphadenopathy	0/28 (0%)	0	1/32 (3.1%)	1	0/30 (0%)	0	0/28 (0%)	0
Monocytopenia	1/28 (3.6%)	1	0/32 (0%)	0	0/30 (0%)	0	0/28 (0%)	0
Leukocytosis	0/28 (0%)	0	0/32 (0%)	0	0/30 (0%)	0	1/28 (3.6%)	1
Monocytosis	0/28 (0%)	0	0/32 (0%)	0	0/30 (0%)	0	1/28 (3.6%)	1
Cardiac disorders
Tachycardia	0/28 (0%)	0	0/32 (0%)	0	2/30 (6.7%)	2	1/28 (3.6%)	1
Extrasystoles	0/28 (0%)	0	0/32 (0%)	0	1/30 (3.3%)	1	0/28 (0%)	0
Ear and labyrinth disorders
Vertigo	1/28 (3.6%)	1	0/32 (0%)	0	0/30 (0%)	0	0/28 (0%)	0
Eye disorders
Conjunctival haemorrhage	0/28 (0%)	0	1/32 (3.1%)	1	0/30 (0%)	0	0/28 (0%)	0
Eye pain	0/28 (0%)	0	0/32 (0%)	0	1/30 (3.3%)	1	0/28 (0%)	0
Gastrointestinal disorders
Nausea	1/28 (3.6%)	1	4/32 (12.5%)	4	3/30 (10%)	11	0/28 (0%)	0
Abdominal pain	1/28 (3.6%)	1	2/32 (6.3%)	2	1/30 (3.3%)	1	0/28 (0%)	0
Abdominal discomfort	1/28 (3.6%)	1	0/32 (0%)	0	1/30 (3.3%)	1	1/28 (3.6%)	2
Abdominal distension	0/28 (0%)	0	1/32 (3.1%)	1	1/30 (3.3%)	1	0/28 (0%)	0
Abdominal pain upper	0/28 (0%)	0	1/32 (3.1%)	1	1/30 (3.3%)	1	0/28 (0%)	0
Duodenitis	0/28 (0%)	0	1/32 (3.1%)	2	0/30 (0%)	0	0/28 (0%)	0
Anal fissure	0/28 (0%)	0	1/32 (3.1%)	1	0/30 (0%)	0	0/28 (0%)	0
Constipation	0/28 (0%)	0	1/32 (3.1%)	1	0/30 (0%)	0	0/28 (0%)	0
Dyspepsia	1/28 (3.6%)	1	0/32 (0%)	0	0/30 (0%)	0	0/28 (0%)	0
Dysphagia	0/28 (0%)	0	1/32 (3.1%)	1	0/30 (0%)	0	0/28 (0%)	0
Flatulence	0/28 (0%)	0	1/32 (3.1%)	1	0/30 (0%)	0	0/28 (0%)	0
Gastritis	0/28 (0%)	0	1/32 (3.1%)	1	0/30 (0%)	0	0/28 (0%)	0
Gastritis erosive	0/28 (0%)	0	1/32 (3.1%)	1	0/30 (0%)	0	0/28 (0%)	0
Oral dysaesthesia	1/28 (3.6%)	1	0/32 (0%)	0	0/30 (0%)	0	0/28 (0%)	0
Toothache	0/28 (0%)	0	1/32 (3.1%)	1	0/30 (0%)	0	0/28 (0%)	0
General disorders
Fatigue	1/28 (3.6%)	1	2/32 (6.3%)	2	5/30 (16.7%)	6	2/28 (7.1%)	2
Injection site erythema	2/28 (7.1%)	2	1/32 (3.1%)	1	2/30 (6.7%)	3	0/28 (0%)	0
Influenza like illness	2/28 (7.1%)	4	1/32 (3.1%)	1	0/30 (0%)	0	0/28 (0%)	0
Hyperthermia	2/28 (7.1%)	2	0/32 (0%)	0	1/30 (3.3%)	2	0/28 (0%)	0
Injection site pruritus	0/28 (0%)	0	1/32 (3.1%)	1	1/30 (3.3%)	3	0/28 (0%)	0
Injection site haematoma	0/28 (0%)	0	1/32 (3.1%)	1	1/30 (3.3%)	1	0/28 (0%)	0
Asthenia	1/28 (3.6%)	1	0/32 (0%)	0	0/30 (0%)	0	0/28 (0%)	0
Chest pain	0/28 (0%)	0	0/32 (0%)	0	1/30 (3.3%)	1	0/28 (0%)	0
Discomfort	0/28 (0%)	0	0/32 (0%)	0	1/30 (3.3%)	1	0/28 (0%)	0
Injection sire paraesthesia	0/28 (0%)	0	0/32 (0%)	0	1/30 (3.3%)	1	0/28 (0%)	0
Injection site reaction	0/28 (0%)	0	1/32 (3.1%)	1	0/30 (0%)	0	0/28 (0%)	0
Thirst	0/28 (0%)	0	0/32 (0%)	0	1/30 (3.3%)	1	0/28 (0%)	0
Non-cardiac chest pain	0/28 (0%)	0	0/32 (0%)	0	0/30 (0%)	0	1/28 (3.6%)	1
Hepatobiliary disorders
Biliary colic	0/28 (0%)	0	0/32 (0%)	0	1/30 (3.3%)	1	0/28 (0%)	0
Immune system disorders
Hypersensitivity	0/28 (0%)	0	0/32 (0%)	0	1/30 (3.3%)	1	0/28 (0%)	0
Perfume sensitivity	0/28 (0%)	0	0/32 (0%)	0	1/30 (3.3%)	1	0/28 (0%)	0
Infections and infestations
Nasopharyngitis	1/28 (3.6%)	1	2/32 (6.3%)	2	2/30 (6.7%)	3	0/28 (0%)	0
Upper respiratory tract infection	1/28 (3.6%)	1	0/32 (0%)	0	1/30 (3.3%)	1	0/28 (0%)	0
Gastroenteritis	0/28 (0%)	0	1/32 (3.1%)	1	0/30 (0%)	0	0/28 (0%)	0
Gastrointestinal infection	0/28 (0%)	0	1/32 (3.1%)	1	0/30 (0%)	0	0/28 (0%)	0
Infected bite	0/28 (0%)	0	1/32 (3.1%)	1	0/30 (0%)	0	0/28 (0%)	0
Influenza	1/28 (3.6%)	1	0/32 (0%)	0	0/30 (0%)	0	0/28 (0%)	0
Pulpitis dental	0/28 (0%)	0	0/32 (0%)	0	1/30 (3.3%)	1	0/28 (0%)	0
Respiratory tract infection	1/28 (3.6%)	1	0/32 (0%)	0	0/30 (0%)	0	0/28 (0%)	0
Injury, poisoning and procedural complications
Arthropod sting	0/28 (0%)	0	1/32 (3.1%)	1	0/30 (0%)	0	0/28 (0%)	0
Investigations
ALT increased	4/28 (14.3%)	4	5/32 (15.6%)	9	9/30 (30%)	12	4/28 (14.3%)	10
AST increased	3/28 (10.7%)	3	7/32 (21.9%)	10	8/30 (26.7%)	12	3/28 (10.7%)	4
GGT increased	0/28 (0%)	0	1/32 (3.1%)	1	2/30 (6.7%)	2	3/28 (10.7%)	3
Lipase increased	1/28 (3.6%)	1	1/32 (3.1%)	2	2/30 (6.7%)	6	0/28 (0%)	0
Amylase increased	1/28 (3.6%)	1	1/32 (3.1%)	1	2/30 (6.7%)	4	0/28 (0%)	0
Haemoglobin decreased	2/28 (7.1%)	3	0/32 (0%)	0	1/30 (3.3%)	1	1/28 (3.6%)	1
Neutrophil count decreased	1/28 (3.6%)	1	1/32 (3.1%)	1	0/30 (0%)	0	1/28 (3.6%)	1
Blood bilirubin increased	0/28 (0%)	0	1/32 (3.1%)	1	1/30 (3.3%)	1	0/28 (0%)	0
INR increased	0/28 (0%)	0	1/32 (3.1%)	1	1/30 (3.3%)	1	0/28 (0%)	0
White blood cell count decreased	1/28 (3.6%)	1	1/32 (3.1%)	1	0/30 (0%)	0	0/28 (0%)	0
Reticulocyte count decreased	0/28 (0%)	0	1/32 (3.1%)	3	0/30 (0%)	0	0/28 (0%)	0
Bilirubin conjugated increased	0/28 (0%)	0	0/32 (0%)	0	1/30 (3.3%)	1	0/28 (0%)	0
ECG abnormal	0/28 (0%)	0	0/32 (0%)	0	1/30 (3.3%)	1	0/28 (0%)	0
Lymphocyte count decreased	0/28 (0%)	0	1/32 (3.1%)	1	0/30 (0%)	0	0/28 (0%)	0
Weight decreased	0/28 (0%)	0	0/32 (0%)	0	1/30 (3.3%)	1	0/28 (0%)	0
APTT prolonged	0/28 (0%)	0	0/32 (0%)	0	0/30 (0%)	0	1/28 (3.6%)	1
Blood creatinine increased	0/28 (0%)	0	0/32 (0%)	0	0/30 (0%)	0	1/28 (3.6%)	1
Platelet count decreased	0/28 (0%)	0	0/32 (0%)	0	0/30 (0%)	0	1/28 (3.6%)	1
Musculoskeletal and connective tissue disorders
Myalgia	0/28 (0%)	0	1/32 (3.1%)	2	1/30 (3.3%)	1	0/28 (0%)	0
Arthralgia	0/28 (0%)	0	1/32 (3.1%)	1	1/30 (3.3%)	1	0/28 (0%)	0
Muscle spasms	0/28 (0%)	0	2/32 (6.3%)	2	0/30 (0%)	0	0/28 (0%)	0
Musculoskeletal stiffness	0/28 (0%)	0	1/32 (3.1%)	1	0/30 (0%)	0	0/28 (0%)	0
Neck pain	0/28 (0%)	0	0/32 (0%)	0	1/30 (3.3%)	1	0/28 (0%)	0
Pain in extremity	0/28 (0%)	0	1/32 (3.1%)	1	0/30 (0%)	0	0/28 (0%)	0
Limb discomfort	0/28 (0%)	0	0/32 (0%)	0	0/30 (0%)	0	1/28 (3.6%)	1
Nervous system disorders
Dizziness	2/28 (7.1%)	2	2/32 (6.3%)	2	3/30 (10%)	4	0/28 (0%)	0
Headache	2/28 (7.1%)	3	2/32 (6.3%)	2	3/30 (10%)	3	0/28 (0%)	0
Migraine	0/28 (0%)	0	1/32 (3.1%)	1	1/30 (3.3%)	1	0/28 (0%)	0
Presyncope	1/28 (3.6%)	1	0/32 (0%)	0	0/30 (0%)	0	0/28 (0%)	0
Somnolence	1/28 (3.6%)	1	0/32 (0%)	0	0/30 (0%)	0	0/28 (0%)	0
Psychiatric disorders
Anxiety	0/28 (0%)	0	0/32 (0%)	0	1/30 (3.3%)	1	0/28 (0%)	0
Nervousness	0/28 (0%)	0	0/32 (0%)	0	1/30 (3.3%)	1	0/28 (0%)	0
Sleep disorder	0/28 (0%)	0	1/32 (3.1%)	1	0/30 (0%)	0	0/28 (0%)	0
Insomnia	0/28 (0%)	0	0/32 (0%)	0	0/30 (0%)	0	1/28 (3.6%)	1
Renal and urinary disorders
Haematuria	0/28 (0%)	0	0/32 (0%)	0	1/30 (3.3%)	1	1/28 (3.6%)	1
Leukocyturia	0/28 (0%)	0	0/32 (0%)	0	1/30 (3.3%)	1	0/28 (0%)	0
Reproductive system and breast disorders
Menstrual disorder	0/28 (0%)	0	0/32 (0%)	0	0/30 (0%)	0	1/28 (3.6%)	1
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	2/28 (7.1%)	2	1/32 (3.1%)	1	2/30 (6.7%)	2	0/28 (0%)	0
Cough	1/28 (3.6%)	1	0/32 (0%)	0	1/30 (3.3%)	1	0/28 (0%)	0
Dyspnoea	1/28 (3.6%)	1	0/32 (0%)	0	0/30 (0%)	0	0/28 (0%)	0
Dyspnoea exertional	0/28 (0%)	0	0/32 (0%)	0	1/30 (3.3%)	1	0/28 (0%)	0
Nasal congestion	0/28 (0%)	0	0/32 (0%)	0	1/30 (3.3%)	1	0/28 (0%)	0
Sinus pain	0/28 (0%)	0	0/32 (0%)	0	1/30 (3.3%)	1	0/28 (0%)	0
Skin and subcutaneous tissue disorders
Alopecia	1/28 (3.6%)	1	0/32 (0%)	0	0/30 (0%)	0	0/28 (0%)	0
Erythema	0/28 (0%)	0	1/32 (3.1%)	1	0/30 (0%)	0	0/28 (0%)	0
Night sweats	0/28 (0%)	0	0/32 (0%)	0	1/30 (3.3%)	1	0/28 (0%)	0
Pruritus	0/28 (0%)	0	0/32 (0%)	0	1/30 (3.3%)	1	0/28 (0%)	0
Rash	1/28 (3.6%)	1	0/32 (0%)	0	0/30 (0%)	0	0/28 (0%)	0
Vitiligo	0/28 (0%)	0	0/32 (0%)	0	1/30 (3.3%)	1	0/28 (0%)	0
Pruritus generalised	0/28 (0%)	0	0/32 (0%)	0	0/30 (0%)	0	1/28 (3.6%)	1
Surgical and medical procedures
Oesophageal variceal ligation	0/28 (0%)	0	1/32 (3.1%)	1	0/30 (0%)	0	0/28 (0%)	0
Vascular disorders
Hypotension	1/28 (3.6%)	1	1/32 (3.1%)	1	0/30 (0%)	0	0/28 (0%)	0
Haematoma	1/28 (3.6%)	1	0/32 (0%)	0	0/30 (0%)	0	0/28 (0%)	0
Hypertension	0/28 (0%)	0	0/32 (0%)	0	1/30 (3.3%)	1	0/28 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.