Clinical Trial of Entecavir/Pegylated Interferon in Immunotolerant Children with Chronic HBV Infection. Hepatitis B Research Network

Study ID
STU 042011-031

Cancer Related
No

Healthy Volunteers
No

Study Sites

  • Children's Medical Center-Dallas

Contact
Laurie Rodgers-Augsutyniak
214-456-6095
laurie.rodgers-augustyniak@childrens.com

Principal Investigator
Norberto Rodriguez-Baez

Summary

Participants with Hepatitis B in the immune tolerant phase and fulfill other entry criteria will be recruited to the study. after obtaining parental/guardian consent and assent, participants will receive entecavir as monotherapy for 8 weeks and then combination therapy with entecavir and pegylated interferon 180 mcg/1.73m2 by weekly subcutaneous injection until week 48. The subcutaneous injections will be give by the patient's parent. education and instruction will be given by the study research nurse regarding the subcutancous injections beginning with the randomization visit. The parents will be provided with instruction and supplies to practice before the first subcutaneous dose is given in clinic at week 8. This will give the parents time to become comfortable with giving the injections. . all children will be followed until week 96 (48 weeks after discontinuation of therapy in the treatment group) at which time the primary outcome will be measured. . Children whose families elect this therapy will be followed with visits and laboratory monitoring as per the original protocol during the treatment phase.

outcome variables include:

a. HBsag loss
b. HBeag loss
c. HBeag seroconversion
d. HBsag seroconversion
e. aLT [?]40 iu/L for males, [?]35 iu/L for females
f. Proportion with HBV Dna [Less Than] 1000 iu/mL
g. Proportion with HBV Dna [Less Than]20 iu/mL (LLoQ of CoBaS
ampliprep/CoBaS TaqMan HBV v2.0 test)
h. Growth parameters (weight, height, BMi, Tanner scores)

The primary endpoint: Safety: adverse events and Serious adverse events through the end of treatment and through the end of follow-up. efficacy endpoint: HBeag loss and HBV Dna levels [?]1,000 iu/mL at the time of last follow up 48 weeks after end-of-treatment (week 96).

2.3. Secondary endpoints
2.3.1. at the end of treatment (week 48):
a. Cumulative HBsag loss
b. HBeag loss
c. HBeag seroconversion
d. HBsag seroconversion
e. aLT [LessThanorequalTo]40 iu/L for males, [LessThanorequalTo]35 iu/L for females
f. HBV Dna [LessThanorequalTo]1000 iu/mL
g. HBV Dna [Less Than]20 iu/mL (LLoQ of CoBaS ampliprep/CoBaS TaqMan HBV v2.0 test)
h. absence of detectable antiviral drug-resistance HBV mutations
i. Growth parameters (weight, height, BMi, Tanner scores)
2.3.2. Sustained end of follow-up responses at 48 weeks after end-of-treatment (week 96):
a. Cumulative HBsag loss
b. HBeag loss
c. HBeag seroconversion
d. HBsag seroconversion
e. aLT [LessThanorequalTo]40 iu/L for males, [LessThanorequalTo]35 iu/L for females
f. HBV Dna [LessThanorequalTo]1000 iu/mL
g. HBV Dna [Less Than]20 iu/mL (LLoQ of CoBaS ampliprep/CoBaS TaqMan HBV v2.0 test)
h. Growth parameters (weight, height, BMi, Tanner scores)
efficacy of combination therapy of entecavir and peginterferon versus no treatment at weeks 48 (end of treatment) and 96 weeks (48 weeks post end of treatment).

The association between sustained off-treatment response at 36 and 48 weeks after end-of treatment and decline in HBsag levels

Tolerability of the combination therapy.

Safety of the combination therapy.



Participant Eligibility

Inclusion criteria
Age 3 to <18 years at time of randomization (day 0).
Documented chronic HBV infection as evidenced by detection of HBsAg in serum for >=24 weeks
prior to randomization or positive HBsAg and negative anti-HBc IgM within 24 weeks of randomization
Presence of HBeAg in serum at the last screening visit within 6 weeks of randomization AND >=24
weeks prior to randomization
Serum HBV DNA >10(7) IU/mL at least 2 occasions at least 12 weeks apart during the 48 weeks
before randomization. The HBV DNA level from the last of the screening visits (within 6 weeks of
randomization) must be used to meet this criterion.
ALT <=60 IU/l in males and <=40 IU/l in females, measured on at least 2 occasions, at screening(within 6 weeks prior to randomization)
and at another time that is at least 12 weeks prior to the screening visit in the 52 weeks
before randomization with no ALT values >60 IU/l in males or >40 IU/l in females within the 52 weeks.
Compensated liver disease, with normal total bilirubin (except if Gilbert[Single Quote]s syndrome), direct
bilirubin <=0.5 mg/dL, INR <=1.5, and serum albumin >=3.5 g/dL.
Creatinine clearance >=90 ml/min.
Absence of hepatocellular carcinoma on liver ultrasound in the past 48 weeks.
Parent/guardian willing to provide informed consent and to adhere to the requirements of the
study.