Trial Outcomes & Findings for A Study to Evaluate Tenofovir Disoproxil Fumarate (DF) in Asian-American Adults With Chronic Hepatitis B Infection (NCT NCT00736190)

NCT ID: NCT00736190

Last Updated: 2011-12-05

Results Overview

Blood samples were collected from study participants for measuring HBV DNA via polymerase chain reaction (PCR) method.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 90 participants
• Primary outcome timeframe: Week 48
• Results posted on: 2011-12-05

Participant Flow

Participant milestones

Measure	A: TDF Tenofovir disoproxil fumarate (TDF) 300 mg by mouth daily
Overall Study STARTED	90
Overall Study COMPLETED	87
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Measure	A: TDF Tenofovir disoproxil fumarate (TDF) 300 mg by mouth daily
Overall Study Pregnancy	1
Overall Study Withdrawal by Subject	1
Overall Study Adverse Event	1

Baseline Characteristics

A Study to Evaluate Tenofovir Disoproxil Fumarate (DF) in Asian-American Adults With Chronic Hepatitis B Infection

Baseline characteristics by cohort

Measure	A: TDF n=90 Participants Tenofovir disoproxil fumarate 300 mg by mouth daily
Age Continuous	36.8 years STANDARD_DEVIATION 10.49 • n=5 Participants
Sex: Female, Male Female	43 Participants n=5 Participants
Sex: Female, Male Male	47 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	90 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	90 participants n=5 Participants
Ethnicity Asian-Chinese	58 Participants n=5 Participants
Ethnicity Asian-Korean	12 Participants n=5 Participants
Ethnicity Asian-Vietnamese	19 Participants n=5 Participants
Ethnicity Asian-Cambodian	1 Participants n=5 Participants
Hepatitis B virus (HBV) deoxyribonucleic acid (DNA)	7.484 log10 copies/mL STANDARD_DEVIATION 1.7678 • n=5 Participants
Hepatitis B e antigen (HBeAg) Positive	53 Participants n=5 Participants
Hepatitis B e antigen (HBeAg) Negative	37 Participants n=5 Participants
Antibody to HBeAg (Anti-HBe) Positive	38 Participants n=5 Participants
Antibody to HBeAg (Anti-HBe) Unknown	52 Participants n=5 Participants
Positive Hepatitis B surface antigen (HBsAg)	90 Participants n=5 Participants
Alanine aminotransferase (ALT); upper limit of normal (ULN) = 34 U/L	103.5 U/L STANDARD_DEVIATION 149.61 • n=5 Participants
ALT (Multiples of ULN)	2.628 multiples of ULN STANDARD_DEVIATION 3.5698 • n=5 Participants
ALT >ULN	67 Participants n=5 Participants
ALT <=ULN	23 Participants n=5 Participants
HBV genotype Genotype B	43 Participants n=5 Participants
HBV genotype Genotype C	47 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 48

Population: The enrolled-and-treated analysis set included participants who were enrolled into the study and received at least one dose of study drug.

Blood samples were collected from study participants for measuring HBV DNA via polymerase chain reaction (PCR) method.

Outcome measures

Measure	Tenofovir DF n=90 Participants 300-mg tablet (marketed formulation) taken orally once daily
Number of Participants With Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) <400 Copies/mL (<69 IU/mL)	74 Participants

SECONDARY outcome

Timeframe: Week 48

Population: The enrolled-and-treated analysis set included participants who were enrolled into the study and received at least one dose of study drug.

Number of participants with normal ALT (at or below the upper limit of normal [ULN] for the central laboratory [34 U/L])at Week 48

Outcome measures

Measure	Tenofovir DF n=90 Participants 300-mg tablet (marketed formulation) taken orally once daily
Number of Participants With Alanine Aminotransferase (ALT) Normal at Week 48	59 Participants

SECONDARY outcome

Timeframe: Week 48

Population: The enrolled-and-treated analysis set included participants who were enrolled into the study, received at least one dose of study drug, and had baseline ALT \> ULN (34 U/L).

A normal value at Week 48 after having elevated ALT at baseline; normal ALT is defined as being at or below the ULN for the central laboratory (34 U/L)

Outcome measures

Measure	Tenofovir DF n=67 Participants 300-mg tablet (marketed formulation) taken orally once daily
Number of Participants With ALT Normalized (Baseline Values > ULN [34 U/L] and <= ULN at a Subsequent Visit) at Week 48	40 participants

SECONDARY outcome

Timeframe: Week 48

Population: The enrolled-and-treated analysis set included participants who were enrolled into the study and received at least one dose of study drug.

Blood samples were collected for evaluating serum chemistry, including determination of ALT, and for measuring HBV DNA via PCR method. Composite endpoints proposed in the protocol included the percentage of participants with HBV DNA < 400 copies/mL (<69 IU/mL) and normal ALT (ALT <= ULN [34 U/L]); and with HBV DNA < 400 copies/mL, normal ALT, and HBeAg loss/seroconversion. Because so few participants lost hepatitis B e antigen (HBeAg) or developed antibody to hepatitis B e antigen (anti-HBe), only the composite endpoint of HBV DNA < 400 copies/mL and normal ALT was analyzed.

Outcome measures

Measure	Tenofovir DF n=90 Participants 300-mg tablet (marketed formulation) taken orally once daily
Number of Participants With Composite Endpoint of Hepatitis B Virus (HBV) DNA <400 Copies/mL (<69 IU/mL) and Normal ALT at Week 48	55 Participants

SECONDARY outcome

Timeframe: Baseline and Week 48

Population: The enrolled-and-treated analysis set included participants who were enrolled into the study and received at least one dose of study drug.

The FibroTest score is used to assess liver fibrosis and is calculated based on a formula including the participant's age and sex and 5 laboratory parameters: alpha 2 macroglobulin, haptoglobin, gamma-glutamyl transferase (GGT), bilirubin, and apolipoprotein A1. Scores can range from 0.00 to 1.00, with higher scores indicating a greater degree of fibrosis.

Outcome measures

Measure	Tenofovir DF n=90 Participants 300-mg tablet (marketed formulation) taken orally once daily
Change From Baseline in FibroTest Value	-0.006 Scores on a scale Standard Deviation 0.1024

SECONDARY outcome

Timeframe: Week 48

HBeAg/HBsAg loss is defined for an individual participant as HBeAg+/HBsAg+ at baseline and HBeAg-/HBsAg- at Week 48. HBeAg/HBsAg serocoversion is defined for an individual participant as HBeAg+/HBsAg+ at baseline and HBeAg-/HBsAg- and anti-HBe+/antibody to hepatitis B surface antigen+ (anti-HBs+) at Week 48.

Outcome measures

Measure	Tenofovir DF n=90 Participants 300-mg tablet (marketed formulation) taken orally once daily
Number of Participants With HBeAg/Hepatitis B Surface Antigen (HBsAg) Loss and Seroconversion HBsAg+ at baseline	90 Participants
Number of Participants With HBeAg/Hepatitis B Surface Antigen (HBsAg) Loss and Seroconversion HBsAg- at baseline	0 Participants
Number of Participants With HBeAg/Hepatitis B Surface Antigen (HBsAg) Loss and Seroconversion HBsAg+ at Week 48	88 Participants
Number of Participants With HBeAg/Hepatitis B Surface Antigen (HBsAg) Loss and Seroconversion HBsAg data missing at Week 48	2 Participants
Number of Participants With HBeAg/Hepatitis B Surface Antigen (HBsAg) Loss and Seroconversion HBeAg+ at baseline	53 Participants
Number of Participants With HBeAg/Hepatitis B Surface Antigen (HBsAg) Loss and Seroconversion HBeAg- at baseline	37 Participants
Number of Participants With HBeAg/Hepatitis B Surface Antigen (HBsAg) Loss and Seroconversion HBeAg loss by Week 48	6 Participants
Number of Participants With HBeAg/Hepatitis B Surface Antigen (HBsAg) Loss and Seroconversion Anti-HBe+ seroconversion by Week 48	6 Participants

SECONDARY outcome

Timeframe: Week 48

Population: The enrolled-and-treated analysis set included participants who were enrolled into the study and received at least one dose of study drug.

Blood samples from study participants were collected for measuring HBV DNA via PCR method.

Outcome measures

Measure	Tenofovir DF n=90 Participants 300-mg tablet (marketed formulation) taken orally once daily
Number of Participants With HBV DNA < 169 Copies/mL (<29 IU/mL) at Week 48	73 Participants

SECONDARY outcome

Timeframe: Week 48

Composite endpoints proposed in the protocol included the percentage of participants with HBV DNA < 400 copies/mL (<69 IU/mL) and normal ALT (ALT <= ULN [34 U/L]); and with HBV DNA < 400 copies/mL, normal ALT, and HBeAg loss/seroconversion. Because so few participants lost HBeAg or seroconverted to anti-HBe, only the composite endpoint of HBV DNA < 400 copies/mL and normal ALT was analyzed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 48

Composite endpoints proposed in the protocol included the percentage of participants with HBV DNA < 400 copies/mL (<69 IU/mL) and normal ALT (ALT <= ULN); and with HBV DNA < 400 copies/mL, normal ALT, and HBeAg loss/seroconversion. Because so few participants lost HBeAg or seroconverted to anti-HBe, only the composite endpoint of HBV DNA < 400 copies/mL and normal ALT was analyzed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 48

Population: 10 participants received \>= 1 dose of study drug, remained viremic (HBV DNA \>= 400 copies/mL) after 48 weeks of TDF treatment, had serum sample for testing, and did not have virologic breakthrough (defined as HBV DNA \>= 400 copies/mL \[confirmed\] after having HBV DNA levels \< 400 copies/mL and/or 1-log10 increase \[confirmed\] in HBV DNA above nadir).

Serum was collected for HBV resistance surveillance, and sequence analysis of the HBV polymerase was assessed through di-deoxy sequencing of baseline and postbaseline samples.

Outcome measures

Measure	Tenofovir DF n=10 Participants 300-mg tablet (marketed formulation) taken orally once daily
Summary of Resistance Surveillance for Participants Without Virologic Breakthrough No changes in HBV pol/RT	6 Participants
Summary of Resistance Surveillance for Participants Without Virologic Breakthrough Changes at polymorphic sites	1 Participants
Summary of Resistance Surveillance for Participants Without Virologic Breakthrough Changes at conserved sites	2 Participants
Summary of Resistance Surveillance for Participants Without Virologic Breakthrough Unable to genotype	1 Participants

SECONDARY outcome

Timeframe: Week 48

Population: 2 participants received \>= 1 dose of study drug, remained viremic (HBV DNA \>= 400 copies/mL) after 48 weeks of TDF treatment, had serum sample for testing, and had virologic breakthrough (defined as HBV DNA \>= 400 copies/mL \[confirmed\] after having HBV DNA levels \< 400 copies/mL and/or 1-log10 increase \[confirmed\] in HBV DNA above nadir).

Serum was collected for HBV resistance surveillance, and sequence analysis of the HBV polymerase was assessed through di-deoxy sequencing of baseline and postbaseline samples.

Outcome measures

Measure	Tenofovir DF n=2 Participants 300-mg tablet (marketed formulation) taken orally once daily
Summary of Resistance Surveillance for Participants With Virologic Breakthrough No changes in HBV pol/RT	2 Participants
Summary of Resistance Surveillance for Participants With Virologic Breakthrough Changes at polymorphic sites	0 Participants
Summary of Resistance Surveillance for Participants With Virologic Breakthrough Changes at conserved sites	0 Participants
Summary of Resistance Surveillance for Participants With Virologic Breakthrough Unable to genotype	0 Participants

SECONDARY outcome

Timeframe: Week 48

Population: 2 participants received \>= 1 dose of study drug, discontinued TDF treatment after Week 24 with HBV DNA \>= 400 copies/mL, and had serum sample for testing.

Serum was collected for HBV resistance surveillance, and sequence analysis of the HBV polymerase was assessed through di-deoxy sequencing of baseline and postbaseline samples.

Outcome measures

Measure	Tenofovir DF n=2 Participants 300-mg tablet (marketed formulation) taken orally once daily
Summary of Resistance Surveillance for Participants Who Discontinued the Study Early No changes in HBV pol/RT	1 Participants
Summary of Resistance Surveillance for Participants Who Discontinued the Study Early Changes at polymorphic sites	0 Participants
Summary of Resistance Surveillance for Participants Who Discontinued the Study Early Changes at conserved sites	0 Participants
Summary of Resistance Surveillance for Participants Who Discontinued the Study Early Unable to genotype	1 Participants

Adverse Events

A: TDF

Serious events: 1 serious events

Other events: 27 other events

Deaths: 0 deaths

Serious adverse events

Measure	A: TDF n=90 participants at risk Tenofovir disoproxil fumarate 300 mg by mouth daily
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic neoplasm malignant	1.1% 1/90 • Number of events 1 • 48 weeks + the follow-up off-study medication period (if applicable). Participants who permanently discontinued study drug were to be followed for 24 weeks off treatment or up to initiation of active treatment, whichever occurred first.

Other adverse events

Measure	A: TDF n=90 participants at risk Tenofovir disoproxil fumarate 300 mg by mouth daily
Infections and infestations Nasopharyngitis	6.7% 6/90 • 48 weeks + the follow-up off-study medication period (if applicable). Participants who permanently discontinued study drug were to be followed for 24 weeks off treatment or up to initiation of active treatment, whichever occurred first.
Gastrointestinal disorders Nausea	5.6% 5/90 • 48 weeks + the follow-up off-study medication period (if applicable). Participants who permanently discontinued study drug were to be followed for 24 weeks off treatment or up to initiation of active treatment, whichever occurred first.
Investigations Weight decreased	5.6% 5/90 • 48 weeks + the follow-up off-study medication period (if applicable). Participants who permanently discontinued study drug were to be followed for 24 weeks off treatment or up to initiation of active treatment, whichever occurred first.
Skin and subcutaneous tissue disorders Rash	5.6% 5/90 • 48 weeks + the follow-up off-study medication period (if applicable). Participants who permanently discontinued study drug were to be followed for 24 weeks off treatment or up to initiation of active treatment, whichever occurred first.
Nervous system disorders Headache	6.7% 6/90 • 48 weeks + the follow-up off-study medication period (if applicable). Participants who permanently discontinued study drug were to be followed for 24 weeks off treatment or up to initiation of active treatment, whichever occurred first.

Additional Information

Eduardo Bruno Martins, MD, DPhil, Sr. Director, Medical Affairs - Hepatitis

Gilead Sciences, Inc.

Phone: 650-522-5792

Email: eduardo.martins@gilead.com

Results disclosure agreements

• Principal investigator is a sponsor employee Investigators may discuss or publish results (without Gilead's confidential information) after all results have been publicly disclosed by/with consent of Gilead or study has been completed \>=2 years. Proposed publication/presentation and destination details must be submitted \>=30 days before submission. The investigator agrees to withhold publication or presentation for an additional 60 days in order to obtain patent protection if deemed necessary.
• Publication restrictions are in place

Restriction type: OTHER