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A Phase 3 Study of Tenofovir Alafenamide (TAF) Compared With Tenofovir Disoproxil Fumarate (TDF) in Patients With HBeAg-negative, Chronic Hepatitis B (CHB): Week 48 Efficacy and Safety Results
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Abstracts
nutritional status was determined through a standardized Mini-Nutritional Assessment (MNA) of a scale from 0-28 points. RESULTS AND CONCLUSION: The mean serum ghrelin was 263.7400.7 and 10871.6 pg/mL in active and nonactive cases, respectively. In the control group, the mean ghrelin was 2028.631333.1 and 438.8226.6 pg/mL in fasting and non-fasting controls, respectively. The association of the serum ghrelin levels between the active cases and the fasting healthy controls was statistically significant (p-value<0.01). The serum leptin was 229.4199 and 359.7 318.5 pg/mL in active and nonactive cases, respectively, while it was 727.36374.18 and 577399.6 pg/mL in fasting and non-fasting controls, respectively. No association was noted between active cases and fasting controls (p-value¼ 0.144). Ghrelin levels were suppressed in both case groups compared to the controls. This could explain the decreased levels of appetite found in the active cases compared with the fasting controls (mean MNA score 18.85 versus 20.83.8, respectively), further emphasizing the therapeutic potential ghrelin could possess. Conflicts of interest: The authors disclose no conflicts.
A Phase 3 Study of Tenofovir Alafenamide (TAF) Compared With Tenofovir Disoproxil Fumarate (TDF) in Patients With HBeAg-negative, Chronic Hepatitis B (CHB): Week 48 Efficacy and Safety Results Henry Lik-Yuen Chan,1 Scott Fung,2 Wai Kay Seto,3 Wan-Long Chuang,4 Chi-Yi Chen,5 Hyung Joon Kim,6 Aric Josun Hui,7 Harry Janssen,8,9 Abhijit Chowdhury,10 Tak Yin Owen Tsang,11 Rajiv Mehta,12 Edward Gane,13 Seng Gee Lim,18 John F. Flaherty,14 Benedetta Massetto,14 Kathryn Kitrinos,14 Phillip Dinh,14 14 Mani Subramanian, John McHutchison,14 14 15 Yiwei Lu, Young-Suk Lim, Sibrat Acharya,16 and Kosh Agarwal17 1 The Chinese University of Hong Kong, Hong Kong, 2Toronto General Hospital, Toronto, ON, Canada, 3Queen Mary Hospital, Hong Kong, 4Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, 5Chiayi Christian Hospital, Chiayi, Taiwan, 6Chung-Ang University Hospital, Seoul, South Korea, 7Alice Ho Miu Ling Nethersole Hospital, Hong Kong, Hong Kong, 8Toronto Western Hospital, Toronto, Ontario, Canada, 9Erasmus Medical Center, Rotterdam, The Netherlands, 10Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India, 11Princess Margaret Hospital, Hong Kong, 12Nirmal Hospital Private Limited, Surat, Gujarat, India, 13Auckland Clinical Studies, Auckland, NZ, 14Gilead Sciences, Foster City, California, 15 Asan Medical Center, Seoul, South Korea, 16All India Institute of Medical Sciences, New Delhi, Delhi, India, 17Kings College Hospital, London, United Kingdom, and 18National University Health System, National University of Singapore, Singapore
Clinical Gastroenterology and Hepatology Vol. 15, No. 1
into lymphoid cells and hepatocytes while lowering circulating levels of TFV by approximately 90% compared to TDF. In patients with HIV, a TAF-containing regimen demonstrated efficacy similar to that of TDF with reduced bone and renal effects (Lancet 2015;385:2606-15). METHODS: In this Phase 3 study (NCT01940471), patients with HBeAg-positive CHB were randomized 2:1 to TAF 25 mg QD or TDF 300 mg QD, each with matching placebo, and treated for 96 weeks. After Week 96, patients receive open label TAF for 48 weeks. The primary efficacy analysis was the percent of patients with HBV DNA <29 IU/mL at Week 48; the study was powered to demonstrate noninferiority in efficacy of TAF compared to TDF, with a 10% margin. Key prespecified secondary safety endpoints were assessed sequentially: changes in hip and spine bone mineral density (BMD), changes in serum creatinine (sCr), and dipstick proteinuria. Markers of bone formation and resorption, and renal tubular function were also assessed. Viral resistance was evaluated by population sequencing those patients who experienced virologic breakthrough, or viremia at the time of discontinuation. RESULTS: 873 patients were randomized and treated at 164 sites in 19 countries. Baseline characteristics included: mean age 38 years, 83% males, 82% Asians, genotypes A through D (7%, 17%, 52%, 23%); 47% had HBV DNA 8 log10 IU/mL, and 26% were treated previously with nucleos(t)ides. Key efficacy and safety end points are summarized in the Table. At Week 48, TAF was non-inferior in efficacy to TDF with virologic response rates of 63.9% with TAF and 66.8% with TDF (difference in proportions: -3.6%, 95% CI, -9.8% to þ2.6%). A greater percentage of patients treated with TAF achieved normalization of serum ALT values. Patients on TAF experienced significantly less declines in hip and spine BMD, and a smaller increase in sCr than TDF; eGFRCG, and renal tubular markers also changed less with TAF. Rates of treatment discontinuations and serious adverse events were low and similar in the two arms. No viral resistance was observed in 22/581 (3.8%) and 11/292 (3.8%) of TAF and TDF patients, respectively, who qualified for testing. CONCLUSION: Compared to TDF 300 mg, the efficacy of TAF 25 mg in patients with HBeAg-positive CHB was noninferior. Safety was also improved, with less change in bone and renal parameters.
BACKGROUND: TAF, a novel prodrug of tenofovir (TFV), is
more stable in plasma and enhances delivery of TFV
Conflicts of interest: The authors disclose no conflicts.
Abstracts
nutritional status was determined through a standardized Mini-Nutritional Assessment (MNA) of a scale from 0-28 points. RESULTS AND CONCLUSION: The mean serum ghrelin was 263.7400.7 and 10871.6 pg/mL in active and nonactive cases, respectively. In the control group, the mean ghrelin was 2028.631333.1 and 438.8226.6 pg/mL in fasting and non-fasting controls, respectively. The association of the serum ghrelin levels between the active cases and the fasting healthy controls was statistically significant (p-value<0.01). The serum leptin was 229.4199 and 359.7 318.5 pg/mL in active and nonactive cases, respectively, while it was 727.36374.18 and 577399.6 pg/mL in fasting and non-fasting controls, respectively. No association was noted between active cases and fasting controls (p-value¼ 0.144). Ghrelin levels were suppressed in both case groups compared to the controls. This could explain the decreased levels of appetite found in the active cases compared with the fasting controls (mean MNA score 18.85 versus 20.83.8, respectively), further emphasizing the therapeutic potential ghrelin could possess. Conflicts of interest: The authors disclose no conflicts.
A Phase 3 Study of Tenofovir Alafenamide (TAF) Compared With Tenofovir Disoproxil Fumarate (TDF) in Patients With HBeAg-negative, Chronic Hepatitis B (CHB): Week 48 Efficacy and Safety Results Henry Lik-Yuen Chan,1 Scott Fung,2 Wai Kay Seto,3 Wan-Long Chuang,4 Chi-Yi Chen,5 Hyung Joon Kim,6 Aric Josun Hui,7 Harry Janssen,8,9 Abhijit Chowdhury,10 Tak Yin Owen Tsang,11 Rajiv Mehta,12 Edward Gane,13 Seng Gee Lim,18 John F. Flaherty,14 Benedetta Massetto,14 Kathryn Kitrinos,14 Phillip Dinh,14 14 Mani Subramanian, John McHutchison,14 14 15 Yiwei Lu, Young-Suk Lim, Sibrat Acharya,16 and Kosh Agarwal17 1 The Chinese University of Hong Kong, Hong Kong, 2Toronto General Hospital, Toronto, ON, Canada, 3Queen Mary Hospital, Hong Kong, 4Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, 5Chiayi Christian Hospital, Chiayi, Taiwan, 6Chung-Ang University Hospital, Seoul, South Korea, 7Alice Ho Miu Ling Nethersole Hospital, Hong Kong, Hong Kong, 8Toronto Western Hospital, Toronto, Ontario, Canada, 9Erasmus Medical Center, Rotterdam, The Netherlands, 10Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India, 11Princess Margaret Hospital, Hong Kong, 12Nirmal Hospital Private Limited, Surat, Gujarat, India, 13Auckland Clinical Studies, Auckland, NZ, 14Gilead Sciences, Foster City, California, 15 Asan Medical Center, Seoul, South Korea, 16All India Institute of Medical Sciences, New Delhi, Delhi, India, 17Kings College Hospital, London, United Kingdom, and 18National University Health System, National University of Singapore, Singapore
Clinical Gastroenterology and Hepatology Vol. 15, No. 1
into lymphoid cells and hepatocytes while lowering circulating levels of TFV by approximately 90% compared to TDF. In patients with HIV, a TAF-containing regimen demonstrated efficacy similar to that of TDF with reduced bone and renal effects (Lancet 2015;385:2606-15). METHODS: In this Phase 3 study (NCT01940471), patients with HBeAg-positive CHB were randomized 2:1 to TAF 25 mg QD or TDF 300 mg QD, each with matching placebo, and treated for 96 weeks. After Week 96, patients receive open label TAF for 48 weeks. The primary efficacy analysis was the percent of patients with HBV DNA <29 IU/mL at Week 48; the study was powered to demonstrate noninferiority in efficacy of TAF compared to TDF, with a 10% margin. Key prespecified secondary safety endpoints were assessed sequentially: changes in hip and spine bone mineral density (BMD), changes in serum creatinine (sCr), and dipstick proteinuria. Markers of bone formation and resorption, and renal tubular function were also assessed. Viral resistance was evaluated by population sequencing those patients who experienced virologic breakthrough, or viremia at the time of discontinuation. RESULTS: 873 patients were randomized and treated at 164 sites in 19 countries. Baseline characteristics included: mean age 38 years, 83% males, 82% Asians, genotypes A through D (7%, 17%, 52%, 23%); 47% had HBV DNA 8 log10 IU/mL, and 26% were treated previously with nucleos(t)ides. Key efficacy and safety end points are summarized in the Table. At Week 48, TAF was non-inferior in efficacy to TDF with virologic response rates of 63.9% with TAF and 66.8% with TDF (difference in proportions: -3.6%, 95% CI, -9.8% to þ2.6%). A greater percentage of patients treated with TAF achieved normalization of serum ALT values. Patients on TAF experienced significantly less declines in hip and spine BMD, and a smaller increase in sCr than TDF; eGFRCG, and renal tubular markers also changed less with TAF. Rates of treatment discontinuations and serious adverse events were low and similar in the two arms. No viral resistance was observed in 22/581 (3.8%) and 11/292 (3.8%) of TAF and TDF patients, respectively, who qualified for testing. CONCLUSION: Compared to TDF 300 mg, the efficacy of TAF 25 mg in patients with HBeAg-positive CHB was noninferior. Safety was also improved, with less change in bone and renal parameters.
BACKGROUND: TAF, a novel prodrug of tenofovir (TFV), is
more stable in plasma and enhances delivery of TFV
Conflicts of interest: The authors disclose no conflicts.