A Multicenter, Open-label, Randomized Clinical Study to A... | NCT03546621

Name	Class
Data Matrix Solutions	OTHER

Label	Type	Description	Intervention Names
Arm A	Experimental	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 Drug: Tenofovir
Arm B	Experimental	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 Drug: Tenofovir
Arm C	Experimental	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 Drug: Tenofovir
Arm D	Active Comparator	tenofovir treatment for 48 weeks	Drug: Tenofovir

Name	Type	Description	Arm Group Labels	Other Names
Myrcludex B	Drug	2 mg, once daily, subcutaneously	Arm A
Myrcludex-B

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

Measure	Description	Time Frame
Durability of HDV RNA Response	Durability of HDV RNA response to 24 weeks post treatment	48 weeks
Combined Response: HDV RNA Response and Normal ALT at Treatment Week 24	Combined response: HDV RNA negativation or ≥2 log decline and normal ALT at treatment week 24

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Age from 18 to 65 years inclusively at the time of signing Informed Consent Form.
Positive serum HBsAg for at least 6 months before Screening.
Positive serum anti-HDV antibody for at least 6 months before screening.
Positive PCR results for serum HDV RNA at Screening.
Patients with liver cirrhosis, irrespective of previous interferon treatment .
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) .
Alanine aminotransferase level >1 x ULN, but less than 10 x ULN.
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.
Negative urine pregnancy test for females of childbearing potential.
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.
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.
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:

Child-Pugh score of B-C or over 6 points.
HCV or HIV coinfection. Subjects with anti-HCV antibodies can be enrolled, if screening HCV RNA test is negative.
Creatinine clearance <60 mL/min.
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.
Any previous or current malignant neoplasms, including hepatic carcinoma.

Name	Affiliation	Role
Heiner Wedemeyer, MD,PhD	Dept. of Gastroenterology, Hepatology and Endocrinology Medizinische Hochschule Hannover	Principal Investigator

PubMed Identifier	Type	Citation	Retractions
38340811	Derived	Allweiss L, Volmari A, Suri V, Wallin JJ, Flaherty JF, Manuilov D, Downie B, Lutgehetmann M, Bockmann JH, Urban S, Wedemeyer H, Dandri M. Blocking viral entry with bulevirtide reduces the number of HDV-infected hepatocytes in human liver biopsies. J Hepatol. 2024 Jun;80(6):882-891. doi: 10.1016/j.jhep.2024.01.035. Epub 2024 Feb 8.
37120031

ID	Title	Description
FG000	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. Myrcludex B: 2 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
FG001

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP_ICF	Yes	Yes	Yes	Study Protocol, Statistical Analysis Plan, and Informed Consent Form: Protocol_v.7.0_28.09.2017_Russia + SAP + ICF

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

HDV RNA Response at Week 24

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

mITT

Posted

Count of Participants

Participants

24 weeks

ID	Title	Description
OG000	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. Myrcludex B: 2 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
OG001	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. Myrcludex-B: 5 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
OG002	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. Myrcludex-B: 10 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
OG003	Arm D	tenofovir treatment for 48 weeks Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg

Units	Counts
Participants	OG00028 OG00132 OG00230 OG003

Title

Denominators

Categories

Title	Measurements
Responder	OG00015 OG00116 OG00223 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001 OG002	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%.	Bonferroni-Holm		<.0001														Superiority

Secondary

Durability of HDV RNA Response

Durability of HDV RNA response to 24 weeks post treatment

mITT

Posted

Count of Participants

Participants

48 weeks

ID	Title	Description
OG000	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. Myrcludex B: 2 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
OG001	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. Myrcludex-B: 5 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
OG002	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. Myrcludex-B: 10 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
OG003

Secondary

Combined Response: HDV RNA Response and Normal ALT at Treatment Week 24

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

mITT

Posted

Count of Participants

Participants

24 weeks

ID	Title	Description
OG000	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. Myrcludex B: 2 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
OG001	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. Myrcludex-B: 5 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
OG002	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. Myrcludex-B: 10 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg

Secondary

Changes in ALT Values

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

mITT

Posted

Mean

Standard Deviation

U/L

24 and 48 weeks

ID	Title	Description
OG000	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. Myrcludex B: 2 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
OG001	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. Myrcludex-B: 5 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
OG002	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. Myrcludex-B: 10 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
OG003

Secondary

Change (Absence of Increase) in Fibrosis Marker

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

mITT

Posted

Mean

Standard Deviation

g/L

24 and 48 weeks

ID	Title	Description
OG000	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. Myrcludex B: 2 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
OG001	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. Myrcludex-B: 5 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
OG002	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. Myrcludex-B: 10 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg

Secondary

Change in Hepatitis B Surface Antigen

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

mITT

Posted

Mean

Standard Deviation

IU/mL

24 and 48 weeks

ID	Title	Description
OG000	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. Myrcludex B: 2 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
OG001	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. Myrcludex-B: 5 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
OG002	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. Myrcludex-B: 10 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg

Secondary

Change in HBV DNA Levels at Week 24 and Week 48 Compared to Baseline

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

mITT

Posted

Mean

Standard Deviation

IU/mL

24 and 48 weeks

ID	Title	Description
OG000	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. Myrcludex B: 2 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
OG001	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. Myrcludex-B: 5 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
OG002	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. Myrcludex-B: 10 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg

Secondary

Absence of a Fibrosis Progression According to the Findings of Transient Elastometry

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

mITT

Posted

Mean

Standard Deviation

kPa

24 weeks

ID	Title	Description
OG000	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. Myrcludex B: 2 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
OG001	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. Myrcludex-B: 5 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
OG002	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. Myrcludex-B: 10 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg

Secondary

Number of Participants With Improvement of Histological Findings According to the Liver Biopsy Results

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.

mITT

Posted

Count of Participants

Participants

24 weeks

ID	Title	Description
OG000	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. Myrcludex B: 2 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
OG001	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. Myrcludex-B: 5 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Total bile acids increased	Investigations	MedDRA (21.0)	Systematic Assessment	EG00012 events8 affected28 at risk EG00120 events12 affected32 at risk EG00224 events15 affected30 at risk EG0038 events6 affected28 at risk
ALT increased	Investigations	MedDRA (21.0)	Systematic Assessment	EG0004 events4 affected28 at risk EG0019 events5 affected32 at risk EG00212 events9 affected30 at risk EG003
AST increased	Investigations	MedDRA (21.0)	Systematic Assessment	EG0003 events3 affected28 at risk EG00110 events7 affected32 at risk EG00212 events8 affected30 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (21.0)	Systematic Assessment	EG0003 events3 affected28 at risk EG00110 events5 affected32 at risk EG0025 events2 affected30 at risk EG003
Fatigue	General disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected28 at risk EG0012 events2 affected32 at risk EG0026 events5 affected30 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected28 at risk EG0014 events4 affected32 at risk EG00211 events3 affected30 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected28 at risk EG0018 events4 affected32 at risk EG0020 events0 affected30 at risk EG003
Dizziness	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected28 at risk EG0012 events2 affected32 at risk EG0024 events3 affected30 at risk EG003
Headache	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0003 events2 affected28 at risk EG0012 events2 affected32 at risk EG0023 events3 affected30 at risk EG003
Leukopenia	Blood and lymphatic system disorders	MedDRA (21.0)	Systematic Assessment	EG0004 events4 affected28 at risk EG0014 events2 affected32 at risk EG0020 events0 affected30 at risk EG003
GGT increased	Investigations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0011 events1 affected32 at risk EG0022 events2 affected30 at risk EG003
Lymphopenia	Blood and lymphatic system disorders	MedDRA (21.0)	Systematic Assessment	EG0003 events3 affected28 at risk EG0010 events0 affected32 at risk EG0020 events0 affected30 at risk EG003
Lipase increased	Investigations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected28 at risk EG0012 events1 affected32 at risk EG0026 events2 affected30 at risk EG003
Amylase increased	Investigations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected28 at risk EG0011 events1 affected32 at risk EG0024 events2 affected30 at risk EG003
Haemoglobin decreased	Investigations	MedDRA (21.0)	Systematic Assessment	EG0003 events2 affected28 at risk EG0010 events0 affected32 at risk EG0021 events1 affected30 at risk EG003
Neutrophil count decreased	Investigations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected28 at risk EG0011 events1 affected32 at risk EG0020 events0 affected30 at risk EG003
Blood bilirubin increased	Investigations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0011 events1 affected32 at risk EG0021 events1 affected30 at risk EG003
INR increased	Investigations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0011 events1 affected32 at risk EG0021 events1 affected30 at risk EG003
White blood cell count decreased	Investigations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected28 at risk EG0011 events1 affected32 at risk EG0020 events0 affected30 at risk EG003
Reticulocyte count decreased	Investigations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0013 events1 affected32 at risk EG0020 events0 affected30 at risk EG003
Bilirubin conjugated increased	Investigations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0010 events0 affected32 at risk EG0021 events1 affected30 at risk EG003
ECG abnormal	Investigations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0010 events0 affected32 at risk EG0021 events1 affected30 at risk EG003
Lymphocyte count decreased	Investigations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0011 events1 affected32 at risk EG0020 events0 affected30 at risk EG003
Weight decreased	Investigations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0010 events0 affected32 at risk EG0021 events1 affected30 at risk EG003
APTT prolonged	Investigations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0010 events0 affected32 at risk EG0020 events0 affected30 at risk EG003
Blood creatinine increased	Investigations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0010 events0 affected32 at risk EG0020 events0 affected30 at risk EG003
Platelet count decreased	Investigations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0010 events0 affected32 at risk EG0020 events0 affected30 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected28 at risk EG0014 events1 affected32 at risk EG0021 events1 affected30 at risk EG003
Lymphocytosis	Blood and lymphatic system disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0012 events2 affected32 at risk EG0020 events0 affected30 at risk EG003
Eosiniphilia	Blood and lymphatic system disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0010 events0 affected32 at risk EG0021 events1 affected30 at risk EG003
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0011 events1 affected32 at risk EG0020 events0 affected30 at risk EG003
Monocytopenia	Blood and lymphatic system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected28 at risk EG0010 events0 affected32 at risk EG0020 events0 affected30 at risk EG003
Leukocytosis	Blood and lymphatic system disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0010 events0 affected32 at risk EG0020 events0 affected30 at risk EG003
Monocytosis	Blood and lymphatic system disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0010 events0 affected32 at risk EG0020 events0 affected30 at risk EG003
Injection site erythema	General disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected28 at risk EG0011 events1 affected32 at risk EG0023 events2 affected30 at risk EG003
Influenza like illness	General disorders	MedDRA (21.0)	Systematic Assessment	EG0004 events2 affected28 at risk EG0011 events1 affected32 at risk EG0020 events0 affected30 at risk EG003
Hyperthermia	General disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected28 at risk EG0010 events0 affected32 at risk EG0022 events1 affected30 at risk EG003
Injection site pruritus	General disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0011 events1 affected32 at risk EG0023 events1 affected30 at risk EG003
Injection site haematoma	General disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0011 events1 affected32 at risk EG0021 events1 affected30 at risk EG003
Asthenia	General disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected28 at risk EG0010 events0 affected32 at risk EG0020 events0 affected30 at risk EG003
Chest pain	General disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0010 events0 affected32 at risk EG0021 events1 affected30 at risk EG003
Discomfort	General disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0010 events0 affected32 at risk EG0021 events1 affected30 at risk EG003
Injection sire paraesthesia	General disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0010 events0 affected32 at risk EG0021 events1 affected30 at risk EG003
Injection site reaction	General disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0011 events1 affected32 at risk EG0020 events0 affected30 at risk EG003
Thirst	General disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0010 events0 affected32 at risk EG0021 events1 affected30 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0010 events0 affected32 at risk EG0020 events0 affected30 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected28 at risk EG0012 events2 affected32 at risk EG0021 events1 affected30 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected28 at risk EG0010 events0 affected32 at risk EG0021 events1 affected30 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0011 events1 affected32 at risk EG0021 events1 affected30 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0011 events1 affected32 at risk EG0021 events1 affected30 at risk EG003
Duodenitis	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0012 events1 affected32 at risk EG0020 events0 affected30 at risk EG003
Anal fissure	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0011 events1 affected32 at risk EG0020 events0 affected30 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0011 events1 affected32 at risk EG0020 events0 affected30 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected28 at risk EG0010 events0 affected32 at risk EG0020 events0 affected30 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0011 events1 affected32 at risk EG0020 events0 affected30 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0011 events1 affected32 at risk EG0020 events0 affected30 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0011 events1 affected32 at risk EG0020 events0 affected30 at risk EG003
Gastritis erosive	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0011 events1 affected32 at risk EG0020 events0 affected30 at risk EG003
Oral dysaesthesia	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected28 at risk EG0010 events0 affected32 at risk EG0020 events0 affected30 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0011 events1 affected32 at risk EG0020 events0 affected30 at risk EG003
Migraine	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0011 events1 affected32 at risk EG0021 events1 affected30 at risk EG003
Presyncope	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected28 at risk EG0010 events0 affected32 at risk EG0020 events0 affected30 at risk EG003
Somnolence	Nervous system disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected28 at risk EG0010 events0 affected32 at risk EG0020 events0 affected30 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected28 at risk EG0012 events2 affected32 at risk EG0023 events2 affected30 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected28 at risk EG0010 events0 affected32 at risk EG0021 events1 affected30 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0011 events1 affected32 at risk EG0020 events0 affected30 at risk EG003
Gastrointestinal infection	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0011 events1 affected32 at risk EG0020 events0 affected30 at risk EG003
Infected bite	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0011 events1 affected32 at risk EG0020 events0 affected30 at risk EG003
Influenza	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected28 at risk EG0010 events0 affected32 at risk EG0020 events0 affected30 at risk EG003
Pulpitis dental	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0010 events0 affected32 at risk EG0021 events1 affected30 at risk EG003
Respiratory tract infection	Infections and infestations	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected28 at risk EG0010 events0 affected32 at risk EG0020 events0 affected30 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0002 events2 affected28 at risk EG0011 events1 affected32 at risk EG0022 events2 affected30 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected28 at risk EG0010 events0 affected32 at risk EG0021 events1 affected30 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected28 at risk EG0010 events0 affected32 at risk EG0020 events0 affected30 at risk EG003
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0010 events0 affected32 at risk EG0021 events1 affected30 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0010 events0 affected32 at risk EG0021 events1 affected30 at risk EG003
Sinus pain	Respiratory, thoracic and mediastinal disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0010 events0 affected32 at risk EG0021 events1 affected30 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0012 events1 affected32 at risk EG0021 events1 affected30 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0011 events1 affected32 at risk EG0021 events1 affected30 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0012 events2 affected32 at risk EG0020 events0 affected30 at risk EG003
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0011 events1 affected32 at risk EG0020 events0 affected30 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0010 events0 affected32 at risk EG0021 events1 affected30 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0011 events1 affected32 at risk EG0020 events0 affected30 at risk EG003
Limb discomfort	Musculoskeletal and connective tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0010 events0 affected32 at risk EG0020 events0 affected30 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected28 at risk EG0010 events0 affected32 at risk EG0020 events0 affected30 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0011 events1 affected32 at risk EG0020 events0 affected30 at risk EG003
Night sweats	Skin and subcutaneous tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0010 events0 affected32 at risk EG0021 events1 affected30 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0010 events0 affected32 at risk EG0021 events1 affected30 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected28 at risk EG0010 events0 affected32 at risk EG0020 events0 affected30 at risk EG003
Vitiligo	Skin and subcutaneous tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0010 events0 affected32 at risk EG0021 events1 affected30 at risk EG003
Pruritus generalised	Skin and subcutaneous tissue disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0010 events0 affected32 at risk EG0020 events0 affected30 at risk EG003
Tachycardia	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0010 events0 affected32 at risk EG0022 events2 affected30 at risk EG003
Extrasystoles	Cardiac disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0010 events0 affected32 at risk EG0021 events1 affected30 at risk EG003
Anxiety	Psychiatric disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0010 events0 affected32 at risk EG0021 events1 affected30 at risk EG003
Nervousness	Psychiatric disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0010 events0 affected32 at risk EG0021 events1 affected30 at risk EG003
Sleep disorder	Psychiatric disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0011 events1 affected32 at risk EG0020 events0 affected30 at risk EG003
Insomnia	Psychiatric disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0010 events0 affected32 at risk EG0020 events0 affected30 at risk EG003
Hypotension	Vascular disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected28 at risk EG0011 events1 affected32 at risk EG0020 events0 affected30 at risk EG003
Haematoma	Vascular disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected28 at risk EG0010 events0 affected32 at risk EG0020 events0 affected30 at risk EG003
Hypertension	Vascular disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0010 events0 affected32 at risk EG0021 events1 affected30 at risk EG003
Biliary colic	Hepatobiliary disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0010 events0 affected32 at risk EG0021 events1 affected30 at risk EG003
Conjunctival haemorrhage	Eye disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0011 events1 affected32 at risk EG0020 events0 affected30 at risk EG003
Eye pain	Eye disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0010 events0 affected32 at risk EG0021 events1 affected30 at risk EG003
Hypersensitivity	Immune system disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0010 events0 affected32 at risk EG0021 events1 affected30 at risk EG003
Perfume sensitivity	Immune system disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0010 events0 affected32 at risk EG0021 events1 affected30 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0010 events0 affected32 at risk EG0021 events1 affected30 at risk EG003
Leukocyturia	Renal and urinary disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0010 events0 affected32 at risk EG0021 events1 affected30 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDRA (21.0)	Systematic Assessment	EG0001 events1 affected28 at risk EG0010 events0 affected32 at risk EG0020 events0 affected30 at risk EG003
Arthropod sting	Injury, poisoning and procedural complications	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0011 events1 affected32 at risk EG0020 events0 affected30 at risk EG003
Oesophageal variceal ligation	Surgical and medical procedures	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0011 events1 affected32 at risk EG0020 events0 affected30 at risk EG003
Menstrual disorder	Reproductive system and breast disorders	MedDRA (21.0)	Systematic Assessment	EG0000 events0 affected28 at risk EG0010 events0 affected32 at risk EG0020 events0 affected30 at risk EG003

ID	Term
D006525	Hepatitis, Viral, Human
D014777	Virus Diseases
D007239	Infections
D012327	RNA Virus Infections
D006505	Hepatitis
D008107	Liver Diseases
D004066	Digestive System Diseases

ID	Term
D063065	Organophosphonates
D009943	Organophosphorus Compounds
D009930	Organic Chemicals
D000225	Adenine
D011687	Purines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds

ID	Title	Description
BG000	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. Myrcludex B: 2 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
BG001	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. Myrcludex-B: 5 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
BG002	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. Myrcludex-B: 10 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
BG003	Arm D	tenofovir treatment for 48 weeks Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg
BG004	Total	Total of all reporting groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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. Myrcludex B: 2 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	28	0	28	18	28
EG001	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. Myrcludex-B: 5 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	32	3	32	19	32
EG002	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. Myrcludex-B: 10 mg, once daily, subcutaneously Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	30	2	30	21	30
EG003	Arm D	tenofovir treatment for 48 weeks Tenofovir: tenofovir disoproxil 245 mg, equivalent to tenofovir disoproxil fumarate 300 mg	28	1	28	13	28