The purpose of this study is to determine the safety and antiviral HBV activity of ACH126, 433 (b-L-Fd4C) in the treatment of adults with lamivudine-resistant chronic Hepatitis B.

Condition	Treatment or Intervention	Phase
Chronic Hepatitis B	Drug: ACH126, 433 (b-L-Fd4C)	Phase II

Further Study Details: 

Expected Total Enrollment:  85

Evaluation of safety and antiviral activity of 3 dose levels of ACH126, 443 over a twelve week treatment in the population described.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

• Adults ≥ 18 years of age
• Chronic HBV infection, known to be HbsAg positive ≥ 6 months
• On lamivudine, either 100 or 150 mg daily for the treatment of chronic hepatitis B infection and
• Exhibit a 2-3 log decrease in HBV DNA levels followed by a rebound of at least 1.5 log HBV DNA or
• Achieved an HBV DNA level of <10,000 copies/mL HBV DNA on at least 2 occasions and have rebounded to > 100,000 copies/mL HBV DNA, or
• Have a demonstrable 3TC resistant genotype regardless of treatment history.
• HBeAG positive
• HIV negative
• Serum ALT ≥1.5 and ≤10x times upper limit of normal
• HGB ≥10g/dl or HCT ≥30% (in the absence of blood transfusions or erythropoietin treatment in the preceding two weeks)
• Platelet count >75,000/mm(^3), (in the absence of ongoing G-CSF therapy)
• Serum creatinine <1.1 times upper limit of normal (ULN)
• Negative radiologic screening test (ultrasound, CT scan or MRI) for hepatocellular carcinoma (HCC) within 6 months prior to entry
• PT/INR<2
• Subjects of reproductive capability must utilize an approved forms of birth control
• All women of child-bearing capability must have a negative serum or urine pregnancy test (minimum sensitivity of 24 IU/L of b-HCG) within 72 hours prior to the start of study medication
• Subjects must be able to provide written informed consent
• Subject must be available for follow-up for a period of 20 weeks

Exclusion Criteria

• HIV infection
• Hepatitis C co-infection
• Alcohol abuse
• Pregnancy or breast-feeding
• Inability to tolerate oral medication
• Any clinical condition or prior therapy that, in the Investigator’s opinion, would make the subject unsuitable for the study or unable to comply with the dosing requirements
• Use of any investigational drug
• Patients with decompensated liver disease
• Use of any concomitant herbal treatments

California
      Huntington Memorial Hospital, Pasadena,  California,  91105,  United States
      Cedars Sinai Medical Center, Los Angeles,  California,  90048,  United States
      University of California-Irvine, Orange,  California,  92868,  United States
      University of California-San Francisco, San Francisco,  California,  94143-0538,  United States
Florida
      University of Miami, Miami,  Florida,  33136,  United States
Illinois
      University of Chicago, Chicago,  Illinois,  60637,  United States
      University of Illinois at Chicago, Chicago,  Illinois,  60612-7323,  United States
Massachusetts
      Beth Israel Deaconess Medical Center, Boston,  Massachusetts,  02215,  United States
New York
      Cornell Weill Medical College, New York,  New York,  10021,  United States
Texas
      The University of Texas, Dallas,  Texas,  75390,  United States
      Baylor Universtiy Medical Center, Dallas,  Texas,  75246,  United States
      Southwest Infectious Disease Associates, P.A., Dallas,  Texas,  75246,  United States
Virginia
      Metropolitan Research, Fairfax,  Virginia,  22031,  United States
Washington
      Unviversity of Washington, Seattle,  Washington,  98195,  United States
Canada, British Columbia
      Vancouver General Hospital, Vancouver,  British Columbia,  V5Z 1L5,  Canada
Canada, Ontario
      Toronto General Hospital, Toronto,  Ontario,  M5G 2C4,  Canada
      Toronto Western Hospital, Toronto,  Ontario,  M5T 2S8,  Canada
Canada, Quebec
      University of Montreal, Montreal,  Quebec,  H2X 3J4,  Canada
China
      The University of Hong Kong, Hong Kong SAR,  China

Study ID Numbers:  ACH443-005
Record last reviewed:  September 2002
Last Updated:  October 13, 2004
Record first received:  June 21, 2002
ClinicalTrials.gov Identifier:  NCT00040144
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08