NCT03546621

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

Completed Phase 2 Results posted Last updated 10 May 2021

What this trial tests

Phase 2 trial testing Myrcludex B in Chronic Hepatitis D Infection With Hepatitis B in 120 participants. Completed in 31 January 2018.

Timeline

16 February 2016

Primary endpoint
31 January 2018

31 January 2018

Quick facts

Lead sponsor	Hepatera Ltd.
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	120
Start date	16 February 2016
Primary completion	31 January 2018
Estimated completion	31 January 2018
Sites	15 locations across Russia, Germany

Drugs / interventions tested

• Myrcludex B — full drug profile →
• Myrcludex-B
• Myrcludex-B
• Tenofovir — full drug profile →

Conditions studied

• Chronic Hepatitis D Infection With Hepatitis B — all drugs for Chronic Hepatitis D Infection With Hepatitis B →

Sponsor

Hepatera Ltd.

Who can join

Adults 18 to 65, any sex, with Chronic Hepatitis D Infection With Hepatitis B. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

HDV RNA Response at Week 24 Primary · 24 weeks

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

Group	Value	95% CI
Arm A	15
Arm B	16
Arm C	23
Arm D	1
Arm A	13
Arm B	16
Arm C	7
Arm D	27

Durability of HDV RNA Response Secondary · 48 weeks

Durability of HDV RNA response to 24 weeks post treatment

Response at Week 24 only

Group	Value	95% CI
Arm A	15
Arm B	16
Arm C	23
Arm D	1

Response at Week 24 and 48

Group	Value	95% CI
Arm A	2
Arm B	1
Arm C	3
Arm D	0

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

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

Week 24

Group	Value	95% CI
Arm A	6
Arm B	9
Arm C	11
Arm D	0
Arm A	22
Arm B	23
Arm C	19
Arm D	28

Week 48

Group	Value	95% CI
Arm A	2
Arm B	1
Arm C	1
Arm D	0
Arm A	26
Arm B	31
Arm C	29
Arm D	28

Changes in ALT Values Secondary · 24 and 48 weeks

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

Change from Baseline to Week 24

Group	Value	95% CI
Arm A	-49.6	± 58.7
Arm B	-79.4	± 84.2
Arm C	-78.9	± 81.1
Arm D	-29.2	± 61.4

Change from Baseline to Week 48

Group	Value	95% CI
Arm A	-1.6	± 72.8
Arm B	-18.2	± 94.4
Arm C	1.4	± 76.0
Arm D	-26.3	± 39.0

Change (Absence of Increase) in Fibrosis Marker Secondary · 24 and 48 weeks

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

Change from Baseline to Week 24

Group	Value	95% CI
Arm A	-0.076	± 0.320
Arm B	0.020	± 0.280
Arm C	0.024	± 0.257
Arm D	-0.141	± 0.607

Change from Baseline to Week 48

Group	Value	95% CI
Arm A	-0.056	± 0.416
Arm B	0.075	± 0.360
Arm C	-0.008	± 0.265
Arm D	-0.031	± 0.485

Change in Hepatitis B Surface Antigen Secondary · 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

Change from Baseline to Week 24

Group	Value	95% CI
Arm A	-0.048	± 0.392
Arm B	0.003	± 0.175
Arm C	0.034	± 0.106
Arm D	0.025	± 0.239

Change from Baseline to Week 48

Group	Value	95% CI
Arm A	-0.138	± 0.288
Arm B	-0.162	± 0.412
Arm C	-0.134	± 0.175
Arm D	-0.070	± 0.186

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

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

Change from Baseline to Week 24

Group	Value	95% CI
Arm A	-0.314	± 0.956
Arm B	-0.484	± 1.106
Arm C	-0.173	± 1.144
Arm D	-0.343	± 1.151

Change from Baseline to Week 48

Group	Value	95% CI
Arm A	-0.244	± 0.828
Arm B	-0.194	± 1.416
Arm C	-0.267	± 1.275
Arm D	-0.257	± 0.979

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

Baseline

Group	Value	95% CI
Arm A	14.45	± 6.37
Arm B	17.18	± 11.49
Arm C	16.00	± 7.37
Arm D	16.20	± 7.83

Change from Baseline to Week 24

Group	Value	95% CI
Arm A	-2.85	± 2.65
Arm B	-2.52	± 6.21
Arm C	-3.38	± 3.83
Arm D	-0.78	± 3.17

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

Ishak fibrosis score

Group	Value	95% CI
Arm A	1
Arm B	1
Arm C	3
Arm D	1
Arm A	3
Arm B	1
Arm C	2
Arm D	1
Arm A	3
Arm B	3
Arm C	2
Arm D	2

Knodell fibrosis score

Group	Value	95% CI
Arm A	1
Arm B	1
Arm C	3
Arm D	2
Arm A	2
Arm B	2
Arm C	2
Arm D	0
Arm A	4
Arm B	2
Arm C	2
Arm D	2

Metavir fibrosis stage

Group	Value	95% CI
Arm A	2
Arm B	1
Arm C	3
Arm D	1
Arm A	1
Arm B	2
Arm C	4
Arm D	2
Arm A	4
Arm B	2
Arm C	0
Arm D	1

Metavir activity grade

Group	Value	95% CI
Arm A	2
Arm B	2
Arm C	3
Arm D	3
Arm A	4
Arm B	1
Arm C	3
Arm D	0
Arm A	1
Arm B	2
Arm C	1
Arm D	1

Histological activity index

Group	Value	95% CI
Arm A	4
Arm B	2
Arm C	3
Arm D	3
Arm A	0
Arm B	1
Arm C	1
Arm D	0
Arm A	3
Arm B	2
Arm C	3
Arm D	1

Adverse events — posted to ClinicalTrials.gov

Time frame: 48 weeks. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm A

Serious: 0/28 (0%)

Deaths: 0/28

Arm B

Serious: 3/32 (9%)

Deaths: 0/32

Arm C

Serious: 2/30 (7%)

Deaths: 0/30

Arm D

Serious: 1/28 (4%)

Deaths: 0/28

Serious adverse events (5 terms)

Reaction	System	Arm A	Arm B	Arm C	Arm D
ALT increased	Investigations	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—
Hepatic cirrhosis	Hepatobiliary disorders	—	—	—	—
Renal colic	Renal and urinary disorders	—	—	—	—
Cholecystitis	Hepatobiliary disorders	—	—	—	—

Other adverse events (111 terms — click to expand)

Reaction	System	Arm A	Arm B	Arm C	Arm D
Total bile acids increased	Investigations	—	—	—	—
ALT increased	Investigations	—	—	—	—
AST increased	Investigations	—	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—	—
Fatigue	General disorders	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—
Neutropenia	Blood and lymphatic system disorders	—	—	—	—
Leukopenia	Blood and lymphatic system disorders	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—
Headache	Nervous system disorders	—	—	—	—
GGT increased	Investigations	—	—	—	—
Lymphopenia	Blood and lymphatic system disorders	—	—	—	—
Lipase increased	Investigations	—	—	—	—
Amylase increased	Investigations	—	—	—	—
Haemoglobin decreased	Investigations	—	—	—	—
Lymphocytosis	Blood and lymphatic system disorders	—	—	—	—
Injection site erythema	General disorders	—	—	—	—
Influenza like illness	General disorders	—	—	—	—
Hyperthermia	General disorders	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Muscle spasms	Musculoskeletal and connective tissue disorders	—	—	—	—
Tachycardia	Cardiac disorders	—	—	—	—
Neutrophil count decreased	Investigations	—	—	—	—
Blood bilirubin increased	Investigations	—	—	—	—
INR increased	Investigations	—	—	—	—
White blood cell count decreased	Investigations	—	—	—	—
Reticulocyte count decreased	Investigations	—	—	—	—
Bilirubin conjugated increased	Investigations	—	—	—	—
ECG abnormal	Investigations	—	—	—	—
Lymphocyte count decreased	Investigations	—	—	—	—
Weight decreased	Investigations	—	—	—	—
APTT prolonged	Investigations	—	—	—	—
Blood creatinine increased	Investigations	—	—	—	—
Platelet count decreased	Investigations	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—
Eosiniphilia	Blood and lymphatic system disorders	—	—	—	—
Lymphadenopathy	Blood and lymphatic system disorders	—	—	—	—
Monocytopenia	Blood and lymphatic system disorders	—	—	—	—

Most-reported serious reactions: ALT increased, Anaemia, Hepatic cirrhosis, Renal colic, Cholecystitis.

Data from ClinicalTrials.gov NCT03546621 adverse events section.

Sponsor's own description

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Safety and efficacy of bulevirtide in combination with tenofovir disoproxil fumarate in patients with hepatitis B virus and hepatitis D virus coinfection (MYR202): a multicentre, randomised, parallel-group, open-label, phase 2 trial.
   Wedemeyer H, Schöneweis K, Bogomolov P, Blank A, et al · · 2023 · cited 96× · PMID 36113537 · DOI 10.1016/s1473-3099(22)00318-8
2. Hepatitis B Virus Cure: Targets and Future Therapies.
   Lee HW, Lee JS, Ahn SH. · · 2020 · cited 75× · PMID 33379331 · DOI 10.3390/ijms22010213
3. New Approaches to the Treatment of Chronic Hepatitis B.
   Alexopoulou A, Vasilieva L, Karayiannis P. · · 2020 · cited 50× · PMID 33019573 · DOI 10.3390/jcm9103187
4. Targeting the Four Pillars of Enterohepatic Bile Salt Cycling; Lessons From Genetics and Pharmacology.
   Kunst RF, Verkade HJ, Oude Elferink RPJ, van de Graaf SFJ. · · 2021 · cited 37× · PMID 33222321 · DOI 10.1002/hep.31651
5. Hepatitis D infection: from initial discovery to current investigational therapies.
   Da BL, Heller T, Koh C. · · 2019 · cited 32× · PMID 32477569 · DOI 10.1093/gastro/goz023
6. Blocking viral entry with bulevirtide reduces the number of HDV-infected hepatocytes in human liver biopsies.
   Allweiss L, Volmari A, Suri V, Wallin JJ, et al · · 2024 · cited 24× · PMID 38340811 · DOI 10.1016/j.jhep.2024.01.035
7. No virologic resistance to bulevirtide monotherapy detected in patients through 24 weeks treatment in phase II and III clinical trials for chronic hepatitis delta.
   Hollnberger J, Liu Y, Xu S, Chang S, et al · · 2023 · cited 17× · PMID 37120031 · DOI 10.1016/j.jhep.2023.04.027
8. A Focused Review on Recent Advances in the Diagnosis and Treatment of Viral Hepatitis.
   Zhang W, Aryan M, Qian S, Cabrera R, et al · · 2021 · cited 16× · PMID 34267829 · DOI 10.14740/gr1405