An open-label, Phase 2, exploratory study to examine the safety and efficacy of inarigivir in non-cirrhotic, hepatitis B e antigen (HBeAg)-negative subjects with chronic HBV infection.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
64
Inarigivir soproxil 200 mg tablets
Continuation of prestudy NUC therapy
University of Calgary
Calgary, Alberta, Canada
GI Research Institute
Vancouver, British Columbia, Canada
LAIR Centre
Vancouver, British Columbia, Canada
Toronto General Hospital
Toronto, Ontario, Canada
Proportion of subjects reporting an adverse event, clinically significant adverse event, or laboratory abnormality
Proportion of subjects in Cohort 1 and 2 reporting an adverse event, clinically significant adverse event, or laboratory abnormality from start to end of treatment, and 30 days after stopping treatment
Time frame: 28 to 52 weeks
Change in quantitative HBsAg (Cohort 1)
Reduction in quantitative hepatitis B surface antigen (HBsAg) by \>0.3 log10 from Baseline to Week 24 of subjects in Cohort 1
Time frame: Baseline to Week 24
Change in the percentage of subjects with loss of HBsAg (Cohort 1)
Percentage of subjects in Cohort 1 with loss of hepatitis B surface antigen (HBsAg) from Baseline to Weeks 24 and 48
Time frame: Baseline to Weeks 24 and Week 48
Percentage of subjects with ALT flares (Cohort 1)
Percentage of subjects in Cohort 1 with alanine transaminase (ALT) flares, defined as ALT \>200 IU or hepatitis B virus (HBV) DNA \>20,000 IU
Time frame: 96 Weeks
Percentage of subjects with suppression of HBV DNA <2000 IU/L (Cohort 1)
Percentage of subjects in Cohort 1 with suppression of hepatitis B virus (HBV) DNA \<2000 IU/L at Weeks 24 and 48
Time frame: Weeks 24
Percentage of subjects with suppression of HBV DNA <2000 IU/L (Cohort 1)
Percentage of subjects in Cohort 1 with suppression of hepatitis B virus (HBV) DNA \<2000 IU/L at Weeks 24 and 48
Time frame: Weeks 48
Percentage of subjects with ALT <40 IU/L (Cohort 1)
Percentage of subjects in Cohort 1 with alanine transaminase (ALT) \<40 IU/L at Weeks 24, 48, 72, and 96
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Toronto Liver Center
Toronto, Ontario, Canada
Barts Health NHS Trust
London, England, United Kingdom
King's College Hospital NHS Foundation Trust
London, England, United Kingdom
Time frame: Weeks 24
Percentage of subjects with ALT <40 IU/L (Cohort 1)
Percentage of subjects in Cohort 1 with alanine transaminase (ALT) \<40 IU/L at Weeks 24, 48, 72, and 96
Time frame: Weeks 48
Percentage of subjects with ALT <40 IU/L (Cohort 1)
Percentage of subjects in Cohort 1 with alanine transaminase (ALT) \<40 IU/L at Weeks 24, 48, 72, and 96
Time frame: Weeks 72
Percentage of subjects with ALT <40 IU/L (Cohort 1)
Percentage of subjects in Cohort 1 with alanine transaminase (ALT) \<40 IU/L at Weeks 24, 48, 72, and 96
Time frame: Weeks 96
Percentage of subjects who lose HBsAg (Cohort 1)
Percentage of subjects in Cohort 1 who lose hepatitis B surface antigen (HBsAg) at Weeks 72 and 96
Time frame: Weeks 72
Percentage of subjects who lose HBsAg (Cohort 1)
Percentage of subjects in Cohort 1 who lose hepatitis B surface antigen (HBsAg) at Weeks 72 and 96
Time frame: Weeks 96
Percentage of subjects with suppression of HBV DNA <2000 IU/L (Cohort 2)
Percentage of subjects in Cohort 2 with suppression of hepatitis B virus (HBV) DNA \<2000 IU/L at Weeks 72 and 96 (off inarigivir treatment)
Time frame: Weeks 72
Percentage of subjects with suppression of HBV DNA <2000 IU/L (Cohort 2)
Percentage of subjects in Cohort 2 with suppression of hepatitis B virus (HBV) DNA \<2000 IU/L at Weeks 72 and 96 (off inarigivir treatment)
Time frame: Weeks 96
Percentage of subjects with ALT <40 IU/L (Cohort 2 )
Percentage of subjects in Cohort 2 with alanine transaminase (ALT) \<40 IU/L at Weeks 72 and 96 (off inarigivir treatment)
Time frame: Weeks 72
Percentage of subjects with ALT <40 IU/L (Cohort 2 )
Percentage of subjects in Cohort 2 with alanine transaminase (ALT) \<40 IU/L at Weeks 72 and 96 (off inarigivir treatment)
Time frame: Weeks 96
Percentage of subjects with HBsAg <1000 IU (Cohort 2)
Percentage of subjects in Cohort 2 with alanine transaminase (ALT) \<40 IU/L at Weeks 72 and 96 (off inarigivir treatment)
Time frame: Weeks 72
Percentage of subjects with HBsAg <1000 IU (Cohort 2)
Percentage of subjects in Cohort 2 with alanine transaminase (ALT) \<40 IU/L at Weeks 72 and 96 (off inarigivir treatment)
Time frame: Weeks 96
Change in serum levels of IFN-α, IFN-γ, TNF, IL-6, IL-10, and IP-10
Fold change from Baseline in markers of innate immunity in serum of IFN-α, IFN-γ, TNF, IL-6, IL-10, and IP-10 in subjects in Cohort 1 and 2
Time frame: Baseline to Week 96 (100 weeks)
Percentage of subjects with HBsAg decline >0.3 log10 (Cohort 2)
Percentage of subjects in Cohort 2 with hepatitis B surface antigen (HBsAg) decline \>0.3 log10 at Weeks 12, 24, 48, 72, and 96
Time frame: Weeks 12, 24, 48, 72, and 96
Percentage of subjects with HBsAg decline >0.5 log10 (Cohort 2)
Percentage of subjects in Cohort 2 with hepatitis B surface antigen (HBsAg) decline \>0.5 log10 at Weeks 12, 24, 48, 72, and 96
Time frame: Weeks 12, 24, 48, 72, and 96
Percentage of subjects with HBsAg loss (Cohort 2)
Percentage of subjects in Cohort 2 with hepatitis B surface antigen (HBsAg) loss at Weeks 24, 48, 72, and 96
Time frame: Weeks 24, 48, 72, and 96
Percentage of subjects with undetectable HBV DNA (Cohort 2)
Percentage of subjects in Cohort 2 with undetectable hepatitis B virus (HBV) DNA at Weeks 24, 48, 72, and 96
Time frame: Weeks 24, 48, 72, and 96
Percentage of subjects who suppress HBsAg <100 IU (Cohort 2)
Percentage of subjects in Cohort 2 who suppress hepatitis B surface antigen (HBsAg) \<100 IU at Weeks 24, 48, 72, and 96
Time frame: Weeks 24, 48, 72, and 96
Change in serum HBV DNA, HBsAg, and HBV RNA in log10 IU/mL (Cohort 2)
Change in serum hepatitis B virus (HBV) DNA, hepatitis B surface antigen (HBsAg), and HBV RNA in log10 IU/mL from Baseline to Weeks 12, 24, 48, 72, and 96 for subjects in Cohort 2
Time frame: Baseline to Week 96 (100 weeks)