Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Entecavir · 18 trials · 8 indications
Suppression=HBV DNA\<50 IU/mL (approximately 300 copies/mL) using the Roche COBAS TaqMan HBV Test for use with the High Pure System assay; seroconversion=undetectable HBeAg and detectable anti-hepatitis B e antibodies. While the analysis of the primary endpoint was based on a randomized sample size of 123 participants (the Primary Cohort), the size of the overall study population was augmented to 180 randomized participants to meet global regulatory requirements.
Virologic response was defined as Hepatitis B virus (HBV) Deoxyribonucleic acid (DNA) less than 50 international units per milliliter (IU/mL); approximately 300 copies/mL. Percentage was calculated as number of participants with virologic response at Week 48 divided by the number of treated participants. Treated participants were evaluated using non-completer (NC) = failure (F). The HBV DNA by polymerase chain reaction (PCR) was measured using the Roche COBAS(REGISTERED) TaqMan - High Pure System (HPS) assay, in a central laboratory. The results were reported in IU/mL, with the limit of quantification (LOQ) = 29 IU/mL and lower limit of detection (LLD) = 6 IU/mL. HBV DNA measurements were transformed by the log10 scale when analyzed as a continuous variable, using log10(LOQ-1) for values below LOQ.
HBV DNA assessments were performed using the Roche COBAS® TaqMan High Pure System (HPS) assay. HBV DNA less than (\<)50 International units per milliliter (IU/mL) = approximately 300 copies/mL. Percentage of participants calculated n/N; n= number of participants with HBV DNA \<50 IU/mL; N = number of participants analyzed.
HBV DNA assessments were performed using the Roche COBAS® TaqMan High+Pure system (HPS) assay. HBV DNA =\> 50 IU/mL = approximately =\> 300 copies/mL.
HBV DNA assessments were performed using the Roche COBAS® TaqMan High+Pure system (HPS) assay. HBV DNA =\> 50 IU/mL = approximately =\> 300 copies/mL.
HBV DNA levels \<50 IU/mL=approximately 300 copies/mL. Analyses of binary efficacy endpoint during on-treatment period focused on participants who received treatment and used the analysis of noncompleter=failure (NC=F). All participants who received treatment were included in the denominator, and participants with missing measurements were counted as nonresponders for the specific endpoints.
Antiviral efficacy, as measured by the mean reduction in serum HBV DNA levels by PCR (log10 copies/mL) at Week 12, adjusted for baseline (Week 12 - baseline). A negative value = improvement.
Mean reduction in serum HBV DNA determined by PCR assay (log10 copies/mL) at Week 24 adjusted for baseline HBV DNA and lamivudine resistance (LVDr) status, based on linear regression analysis.
An AE is a new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not be causally related to treatment. An SAE is an unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening or disabling. ALT=alanine transaminase; ULN=upper limit of normal.
Hemoglobin (g/dL): Grade (Gr) 1=9.5-11.0; Gr 2=8.0-\<9.5; Gr 3=6.5-\<8.0; Gr 4=\<6.5 White blood cells (cells/mm\^3): Gr 1=2,500-\<4,000; Gr 2=1,000-\<2,500; Gr 3=800-\<1,000; Gr 4=\<800. Neutrophils (cells/mm\^3): Gr 1=1000-\<1500; Gr 2=750-\<1000; Gr 3=500-\<750; Gr 4=\<500. Platelets (cells/mm\^3): Gr 1=75,000-99,000; Gr 2=50,000-\<75,000; Gr 3=20,000-\<50,000; Gr 4=\<20,000. Prothrombin time (seconds): Gr 1=1.01-\<1.26\*ULN; Gr 2=1.26-\<1.51 \*ULN; Gr 3=1.51-3\*ULN; Gr 4=\>3\*ULN. INR: Gr 1=1.24-1.5; Gr 2=1.5-2; Gr 3=2-3; Gr 4=\>3. INR=international normalized ratio; ULN=upper limit of normal. .
Amylase: Grade 1=1.10-\<1.40\*ULN; Grade 2=1.40-\< 2.10\*ULN; Grade 3=2.10-5.00\*ULN; Grade 4=\>5.00\*ULN. Lipase: Grade 1.1-\<1.4\*ULN; Grade 2=1.4-\<2.1\*ULN; Grade 3=2.1-5.0\*ULN; Grade 4=\>5.0\*ULN. Creatinine: Grade 1=1.10-\< 1.60\*ULN; Grade 2=1.60-\<3.10\*ULN; Grade 3=3.10-6.00\*ULN; Grade 4=\>6.00\*ULN. Blood urea nitrogen (BUN): Grade 1=1.25-\<2.60\*ULN; Grade 2=2.60-\<5.10\*ULN; Grade 3=5.10-10\*ULN; Grade 4=\>10\*ULN. ULN=upper limit of normal.
Hypochloremia: Grade (Gr) 1=90-93; Gr 2=85-\<90; Gr 3=80-\<85; Gr 4=40-\<80. Hyperchloremia: Gr 1=113-\<117; Gr 2=117-\<121; Gr 3=121-125; Gr 4\>125. Hypocarbia: Gr 1=19-21; Gr 2=15-\<19; Gr 3=41-45; Gr 4=\>45. Hypercarbia: Gr 1=31-36; Gr 2=37-40; Gr 3=41-45; Gr 4=\>45. Hyponatremia: Gr 1=130-132; Gr 2=123-\<130; Gr 3=116-\<123; Gr 4\<116. Hypernatremia: Gr 1=148-\<151; Gr 2=151-\<158; Gr 3=158-165; Gr 4=\>165. Hypokalemia: Gr 1=3-3.4; Gr 2=2.5-\<3; Gr 3=2-\<2.5; Gr 4=\<2. Hyperkalemia: Gr 1=5.6-\<6.1; G2=6.1-\<6.6; Gr 3=6.6-7; Gr 4=\>7. Hypoglycemia: Gr 1=55-64; Gr 2=40-\<55; Gr 3=30-\< 40; G4=-\<30. Hyperglycemia: Gr 1=116-\<161; Gr 2=161-\<251; Gr 3=251-500; Gr 4\>500.
An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening or disabling. AST=aspartate aminotransferase; ULN=upper limit of normal.
An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. CTC Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening or disabling. ALT=alanine aminotransferase; ULN=upper limit of normal.
The Amendment 11 Cohort consisted of participants who were hepatitis B e antigen (HBeAg) negative and who had compensated liver disease, a minimum of 192 weeks (4 years) of treatment with entecavir, HBV DNA \<300 copies/mL by PCR assay for ≥48 weeks before end of dosing and on the last observed result ≤24 weeks prior to end of dosing, and serum ALT levels ≤1.0\*ULN at the end of study drug dosing.ALT=alanine aminotransferase; ULN=upper limit of normal.
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Medical Dictionary for Regulatory Activities (MedDRA) version 16.0 was used.
| Arm | Type | Description |
|---|---|---|
| Entecavir | ACTIVE_COMPARATOR | Participants received entecavir, 0.015 mg/kg up to 0.5 mg, once daily, for 96 to 144 weeks, depending on response |
| Placebo | PLACEBO_COMPARATOR | Participants received placebo, 0 mg, once daily, for 48 to 96 weeks, depending on response |
| Entecavir + Tenofovir | EXPERIMENTAL | - |
| Adefovir + Lamivudine | ACTIVE_COMPARATOR | - |
| Entecavir + Adefovir | ACTIVE_COMPARATOR | - |
| TDF 0.5 mg | EXPERIMENTAL | TDF=tenofovir |
| ETV 0.5 mg +TDF 300 mg | EXPERIMENTAL | ETV=entecavir; TDF=tenofovir |
| A1 | ACTIVE_COMPARATOR | - |
| A2 | ACTIVE_COMPARATOR | - |
| Entecavir 0.5 | ACTIVE_COMPARATOR | - |
| Entecavir 1.0 | ACTIVE_COMPARATOR | - |
| Entecavir (0.01 mg) | EXPERIMENTAL | - |
| Entecavir (0.1 mg) | EXPERIMENTAL | - |
| Entecavir (0.5 mg) | EXPERIMENTAL | - |
| Entecavir (1mg) | EXPERIMENTAL | - |
| Entecavir, 1.0 mg, with or without lamivudine | EXPERIMENTAL | - |
| Arm 1: Entecavir | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Entecavir | DRUG | Tablets/oral solution, 0.015 mg/kg up to 0.5 mg, administered orally, once daily, for 96 to144 weeks, depending on response |
| Placebo | DRUG | Tablets/oral solution, 0 mg, administered orally, once daily, for 48 to 96 weeks, depending on response |
| Tenofovir | DRUG | Tablets, Oral, 300 mg, once daily, 96 weeks |
| Adefovir | DRUG | Tablets, Oral, 10mg, once daily, 100 weeks |
| Lamivudine | DRUG | Tablets, Oral, 100mg, once daily, 100 weeks |
| Entecavir + Tenofovir | DRUG | Tablets, Oral, ETV = 0.5 mg + TFV = 300 mg, once daily, 100 weeks |
| Entecavir (ETV) | DRUG | Tablets, Oral, 1 mg once daily, 96 weeks from the time the last patient is randomized |
| Adefovir (ADV) | DRUG | Tablets, Oral, 10 mg, once daily, 96 weeks from the time the last patient is randomized |
Key Inclusion Criteria * Males and females, aged 2 to \<18 years * Hepatitis B surface antigen-positive * Detectable hepatitis B e (HBe) antigen, and no detectable anti-HBe antibodies * Alanine aminotransferase (ALT) 1.5 to \<10 times the upper limit of normal at screening and within 8 to 24 weeks ...
Entecavir is used for the treatment of chronic hepatitis B virus (HBV) infection, including chronic hepatitis B in pediatric patients. It is a small molecule antiviral drug being developed by Bristol-Myers Squibb Company (BMY) for infectious disease indications.
Entecavir is a nucleoside analog reverse transcriptase inhibitor that targets the hepatitis B virus polymerase. By inhibiting this enzyme, it blocks viral DNA replication, reducing the amount of virus in the body. This mechanism is specific to HBV and does not affect human DNA polymerase.
Entecavir is developed by Bristol-Myers Squibb Company, which trades under the ticker BMY on the New York Stock Exchange. The company is conducting clinical trials to evaluate the drug's safety and efficacy in patients with chronic hepatitis B.
Entecavir is in Phase 3 clinical development for chronic hepatitis B. It has completed eight trials with a total enrollment of 1,471 participants. The drug is investigational and not yet approved by regulatory authorities, as it is still undergoing clinical evaluation.
Entecavir has been studied in several Phase 3 trials, including NCT00410072 comparing entecavir plus tenofovir combination therapy to entecavir monotherapy in naive subjects, and NCT00410202 evaluating entecavir plus adefovir in lamivudine-resistant patients. A pediatric study (NCT00423891) and a rollover study in China (NCT00975091) have also been completed.
Entecavir is the generic name for the drug marketed as Baraclude. The clinical trials referenced use the name entecavir, but Baraclude is the brand name under which the drug is sold. Both names refer to the same antiviral medication for chronic hepatitis B.