Trial Outcomes & Findings for Study of EYP001a to Assess Its Safety and Anti-viral Effect in CHB Patients in Combination With NA (ETV or TD) (NCT NCT04465916)

NCT ID: NCT04465916

Last Updated: 2022-11-02

Results Overview

Efficacy of Vonafexor on top of NA assessed as HBsAg decline (Δ log10) from Day 1 to Week 16 of treatment

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

26 participants

Primary outcome timeframe

LS mean at week 16 (Day 1, Week 2, Week 4, Week 6, Week 8, Week 10, Week 12, Week 14, and Week 16)

Results posted on

2022-11-02

Participant Flow

Participant milestones

Participant milestones
Measure	Experimental Arm Experimental Arm: EYP001a 200 mg daily + Nucleotide analogue daily (37 patients) EYP001a: Oral tablets Nucleotide analogue (Entecavir or Tenofovir Disoproxil): Oral tablets	Control Arm Control Arm: Placebo daily + Nucleotide analogue daily (12 patients) Placebo: Oral tablets Nucleotide analogue (Entecavir or Tenofovir Disoproxil): Oral tablets
Overall Study STARTED	19	7
Overall Study COMPLETED	19	6
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Experimental Arm Experimental Arm: EYP001a 200 mg daily + Nucleotide analogue daily (37 patients) EYP001a: Oral tablets Nucleotide analogue (Entecavir or Tenofovir Disoproxil): Oral tablets	Control Arm Control Arm: Placebo daily + Nucleotide analogue daily (12 patients) Placebo: Oral tablets Nucleotide analogue (Entecavir or Tenofovir Disoproxil): Oral tablets
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Study of EYP001a to Assess Its Safety and Anti-viral Effect in CHB Patients in Combination With NA (ETV or TD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Experimental Arm n=19 Participants Experimental Arm: EYP001a Dose A QD + NA daily (37 patients) EYP001a: Oral tablets Nucleotide analogue (Entecavir or Tenofovir Disoproxil): Oral tablets	Control Arm n=7 Participants Control Arm: Placebo + NA daily (12 patients) Placebo: Oral tablets Nucleotide analogue (Entecavir or Tenofovir Disoproxil): Oral tablets	Total n=26 Participants Total of all reporting groups
Age, Continuous	45.16 years STANDARD_DEVIATION 8.32 • n=5 Participants	46.29 years STANDARD_DEVIATION 8.46 • n=7 Participants	45.46 years STANDARD_DEVIATION 8.20 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	6 Participants n=7 Participants	20 Participants n=5 Participants
Race/Ethnicity, Customized Asian	19 participants n=5 Participants	5 participants n=7 Participants	24 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized White	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Weight	68.821 kg STANDARD_DEVIATION 11.293 • n=5 Participants	82.857 kg STANDARD_DEVIATION 21.084 • n=7 Participants	72.600 kg STANDARD_DEVIATION 15.454 • n=5 Participants
Height	168.763 cm STANDARD_DEVIATION 9.333 • n=5 Participants	172.529 cm STANDARD_DEVIATION 11.342 • n=7 Participants	169.777 cm STANDARD_DEVIATION 9.823 • n=5 Participants

PRIMARY outcome

Timeframe: LS mean at week 16 (Day 1, Week 2, Week 4, Week 6, Week 8, Week 10, Week 12, Week 14, and Week 16)

Efficacy of Vonafexor on top of NA assessed as HBsAg decline (Δ log10) from Day 1 to Week 16 of treatment

Outcome measures

Outcome measures
Measure	Experimental Arm n=19 Participants Experimental Arm: EYP001a Dose A QD + NA daily (37 patients) EYP001a: Oral tablets Nucleotide analogue (Entecavir or Tenofovir Disoproxil): Oral tablets	Control Arm n=7 Participants Control Arm: Placebo + NA daily (12 patients) Placebo: Oral tablets Nucleotide analogue (Entecavir or Tenofovir Disoproxil): Oral tablets
HBsAg Change (Δ log10) From Day 1 to Week 16 of Treatment	-0.029 log10 IU/mL Standard Error 0.0195	-0.066 log10 IU/mL Standard Error 0.0348

SECONDARY outcome

Timeframe: 40 weeks

Virologic failure rate (breakthrough)2 of HBV-DNA (% patients with a confirmed quantifiable HBV DNA increase of ≥ 1log10 HBV DNA copies/mL above LLOQ3) assessed at Week 16 of treatment period and Weeks 20, 28 and 40 during follow-up period

Outcome measures

Outcome measures
Measure	Experimental Arm n=19 Participants Experimental Arm: EYP001a Dose A QD + NA daily (37 patients) EYP001a: Oral tablets Nucleotide analogue (Entecavir or Tenofovir Disoproxil): Oral tablets	Control Arm n=6 Participants Control Arm: Placebo + NA daily (12 patients) Placebo: Oral tablets Nucleotide analogue (Entecavir or Tenofovir Disoproxil): Oral tablets
Virologic Failure Rate Week 28	0 participants	0 participants
Virologic Failure Rate Week 40	0 participants	0 participants
Virologic Failure Rate Week 16	0 participants	0 participants
Virologic Failure Rate Week 20	0 participants	0 participants

Adverse Events

Experimental Arm

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Control Arm

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Pietro Scalfaro

ENYO Pharma SA

Phone: +33437700219

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The data may be considered for publication in a scientific journal or for reporting at a scientific meeting. Each Investigator is obligated to keep data pertaining to the study confidential. The Investigator must consult with the Sponsor before any study data are submitted for publication. The Sponsor reserves the right to deny publication rights until mutual agreement on the content, format, interpretation of data in the manuscript, and journal selected for publication are achieved.
Publication restrictions are in place

Restriction type: OTHER

Other adverse events
Measure	Experimental Arm n=19 participants at risk Experimental Arm: EYP001a Dose A QD + NA daily (37 patients) EYP001a: Oral tablets Nucleotide analogue (Entecavir or Tenofovir Disoproxil): Oral tablets	Control Arm n=7 participants at risk Control Arm: Placebo + NA daily (12 patients) Placebo: Oral tablets Nucleotide analogue (Entecavir or Tenofovir Disoproxil): Oral tablets
Vascular disorders Flushing	5.3% 1/19 • Number of events 1 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.	0.00% 0/7 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.
Vascular disorders Hypertension	5.3% 1/19 • Number of events 1 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.	0.00% 0/7 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.
Investigations Serum ferritin decreased	0.00% 0/19 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.	14.3% 1/7 • Number of events 1 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.
Investigations White blood cell count decreased	0.00% 0/19 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.	14.3% 1/7 • Number of events 1 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.
Cardiac disorders Atrioventricular block first degree	0.00% 0/19 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.	14.3% 1/7 • Number of events 1 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.
Respiratory, thoracic and mediastinal disorders Emphysema	5.3% 1/19 • Number of events 1 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.	0.00% 0/7 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	5.3% 1/19 • Number of events 2 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.	0.00% 0/7 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.
Respiratory, thoracic and mediastinal disorders Throat irritation	5.3% 1/19 • Number of events 1 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.	0.00% 0/7 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.3% 1/19 • Number of events 1 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.	0.00% 0/7 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.
Blood and lymphatic system disorders Neutropenia	0.00% 0/19 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.	14.3% 1/7 • Number of events 1 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.
Nervous system disorders Headache	5.3% 1/19 • Number of events 1 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.	0.00% 0/7 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.
Nervous system disorders Syncope	5.3% 1/19 • Number of events 2 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.	0.00% 0/7 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.
General disorders Fatigue	5.3% 1/19 • Number of events 2 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.	0.00% 0/7 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.
General disorders Influenza like illness	5.3% 1/19 • Number of events 1 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.	0.00% 0/7 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.
General disorders Pain	5.3% 1/19 • Number of events 1 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.	0.00% 0/7 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.
General disorders Vaccination site discomfort	5.3% 1/19 • Number of events 1 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.	0.00% 0/7 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.
Gastrointestinal disorders Abdominal pain	5.3% 1/19 • Number of events 1 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.	0.00% 0/7 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.
Gastrointestinal disorders Abdominal pain lower	0.00% 0/19 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.	14.3% 1/7 • Number of events 1 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.
Gastrointestinal disorders Chronic gastritis	5.3% 1/19 • Number of events 1 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.	0.00% 0/7 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.
Gastrointestinal disorders Diarrhoea	15.8% 3/19 • Number of events 4 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.	0.00% 0/7 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.
Gastrointestinal disorders Faeces discoloured	5.3% 1/19 • Number of events 1 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.	0.00% 0/7 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.
Gastrointestinal disorders Hiatus hernia	0.00% 0/19 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.	14.3% 1/7 • Number of events 1 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.
Gastrointestinal disorders Nausea	10.5% 2/19 • Number of events 2 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.	0.00% 0/7 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.
Gastrointestinal disorders Oesophagitis	0.00% 0/19 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.	14.3% 1/7 • Number of events 1 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.
Skin and subcutaneous tissue disorders Pruritus	78.9% 15/19 • Number of events 19 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.	14.3% 1/7 • Number of events 1 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.
Musculoskeletal and connective tissue disorders Arthralgia	5.3% 1/19 • Number of events 1 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.	0.00% 0/7 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.
Musculoskeletal and connective tissue disorders Muscular weakness	10.5% 2/19 • Number of events 3 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.	0.00% 0/7 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.
Infections and infestations Bronchitis	5.3% 1/19 • Number of events 1 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.	0.00% 0/7 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.
Infections and infestations Urinary tract infection	5.3% 1/19 • Number of events 1 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.	0.00% 0/7 • After the first dose of study drug until W40 Participants received either Entecavir or Tenofovir Disoproxil Fumarate in each Arm/Group combined with Placebo or EYP001. Entecavir and Tenofovir Disoproxil Fumarate are both NA and are therapeutically equivalent. Therefore safety results are presented for Experimental Arm and Control Arm irrespective of NA therapy taken.