J Korean Med Sci.  2022 Mar;37(11):e92. 10.3346/jkms.2022.37.e92.

A Multi-Center, Double-Blind Randomized Controlled Phase III Clinical Trial to Evaluate the Antiviral Activity and Safety of DA-2802 (Tenofovir Disoproxil Orotate) and Viread (Tenofovir Disoproxil Fumarate) in Chronic Hepatitis B Patients

  • 1Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
  • 2Department of Internal Medicine, Division of Gastroenterology, Gil Medical Center, Gachon University College of Medicine, Incheon, Korea
  • 3Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
  • 4Department of Internal Medicine, Catholic University of Korea College of Medicine, Seoul, Korea
  • 5Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
  • 6Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
  • 7Department of Internal Medicine, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan, Korea
  • 8Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea
  • 9Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
  • 10Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
  • 11Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
  • 12Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
  • 13Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
  • 14Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
  • 15Department of Internal Medicine, Wonkwang University School of Medicine, Iksan, Korea
  • 16Department of Internal Medicine, Ilsan Paik Hospital, Inje University College of Medicine, Ilsan, Korea
  • 17Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
  • 18Department of Gastroenterology, Jeonbuk National University Hospital, Jeonju, Korea
  • 19Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Korea
  • 20Department of Internal Medicine, School of Medicine, Chungnam National University, Daejeon, Korea


Tenofovir disoproxil fumarate (TDF, Viread® ) had been used as a standard treatment option of chronic hepatitis B (CHB). This clinical trial was conducted to evaluate the efficacy and safety of DA-2802 (tenofovir disoproxil orotate) compared to TDF.
The present study was a double blind randomized controlled trial. Patients with CHB were recruited from 25 hospitals in Korea and given DA-2802 at a dose of 319 mg once daily or Viread® at a dose of 300 mg once daily for 48 weeks from March 2017 to January 2019. Change in hepatitis B virus (HBV) DNA level at week 48 after dosing compared to baseline was the primary efficacy endpoint. Secondary efficacy endpoints were proportions of subjects with undetectable HBV DNA, those with normal alanine aminotransferase (ALT) levels, and those with loss of hepatitis B envelop antigen (HBeAg), those with loss of hepatitis B surface antigen (HBsAg). Adverse events (AEs) were also investigated.
A total of 122 patients (DA-2802 group: n = 61, Viread® group: n = 61) were used as full analysis set for efficacy analysis. Mean age, proportion of males, laboratory results and virologic characteristics were not different between the two groups. The change in HBV DNA level at week 48 from baseline was −5.13 ± 1.40 in the DA-2802 group and −4.97 ± 1.40 log 10 copies/mL in the Viread® group. The analysis of primary endpoint using the nonparametric analysis of covariance showed statistically significant results (P < 0.001), which confirmed non-inferiority of DA-2802 to Viread® by a prespecified noninferiority margin of 1. The proportion of undetectable HBV DNA was 78.7% in the DA-2802 group and 75.4% in the Viread® group (P = 0.698). The proportion of subjects who had normal ALT levels was 75.4% in the DA-2802 group and 73.3% in the Viread® group (P = 0.795). The proportion of those with HBeAg loss was 8.1% in the DA-2802 group and 10.8% in the Viread® group (P = 1.000). No subject showed HBsAg loss. The frequency of AEs during treatment was similar between the two groups. Most AEs were mild to moderate in severity.
DA-2802 is considered an effective and safe treatment for patients with CHB.


Tenofovir; Hepatitis B; Chronic; Hepatitis B Virus; Efficacy; Safety


  • Fig. 1 Flow chart showing the enrollment of patients. Full analysis set consisted of 61 subjects in the DA-2802 group and 61 subjects in the Viread® group. Sixty subjects in the DA-2802 group and 51 subjects in the Viread® group completed the present study.

  • Fig. 2 Comparing the change in HBV DNA level (log10) at week 48 after dosing from baseline.HBV = hepatitis B virus.

  • Fig. 3 Comparing the pattern of decreasing HBV DNA level during treatment.HBV = hepatitis B virus.

  • Fig. 4 Comparing secondary efficacy endpoints. (A) Proportion of those with undetectable HBV DNA, (B) Proportion of those with ALT normalization.HBV = hepatitis B virus, ALT = alanine aminotransferase.

  • Fig. 5 Comparing the change of (A) Hip T score, (B) Spine T score, (C) Creatinine, (D) eGFR, and (E) Serum phosphate level.eGFR = estimation of glomerular filtration rate.


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