Phase 3
N=161
A Study of Pegasys (Peginterferon Alfa-2a) Versus Untreated Control in Children With HBeAg Positive Chronic Hepatitis B
Hepatitis B, Chronic
Bottom Line
View on ClinicalTrials.gov: NCT01519960 ↗Enrolled (actual)
161
Serious AEs
2.3%
Results posted
Aug 2016
Primary outcome: Primary: Percentage of Participants With HBeAg Seroconversion at 24 Weeks After End of Treatment (EOT)/POP in Groups A and B — 25.7; 6 percentage of participants — p== 0.0043
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- peginterferon alfa-2a [Pegasys] (Drug)
- Age
- Pediatric · 3+ yrs
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- Jul 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With HBeAg Seroconversion at 24 Weeks After End of Treatment (EOT)/POP in Groups A and B |
25.7; 6 | = 0.0043 sig |
| SECONDARY Percentage of Participants With Loss of HBeAg at 24 Weeks After EOT/POP in Groups A and B |
25.7; 6 | — |
| SECONDARY Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Seroconversion at 24 Weeks After EOT/POP in Groups A and B |
7.9; 0 | — |
| SECONDARY Percentage of Participants With Normal ALT at 24 Weeks After EOT/POP in Groups A and B |
51.5; 12 | — |
| SECONDARY Percentage of Participants With HBV Deoxyribonucleic Acid (DNA) <20,000 International Units Per Milliliter (IU/mL) at 24 Weeks After EOT/POP in Groups A and B |
33.7; 4 | — |
| SECONDARY Percentage of Participants With HBV DNA <2,000 IU/mL at 24 Weeks After EOT/POP in Groups A and B |
28.7; 2 | — |
| SECONDARY Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at 24 Weeks After EOT/POP in Groups A and B |
22.8; 4 | — |
| SECONDARY Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at 24 Weeks After EOT/POP in Groups A and B |
19.8; 2 | — |
| SECONDARY Percentage of Participants With HBeAg Seroconversion at EOT/POP in Groups A and B |
7.9; 6 | — |
| SECONDARY Percentage of Participants With Loss of HBeAg at EOT/POP in Groups A and B |
8.9; 6 | — |
| SECONDARY Percentage of Participants With HBsAg Seroconversion at EOT/POP in Groups A and B |
6.9; 0 | — |
| SECONDARY Percentage of Participants With Loss of HBsAg at EOT/POP in Groups A and B |
10.9; 0 | — |
| SECONDARY Percentage of Participants With Normal ALT at EOT/POP in Groups A and B |
18.8; 22 | — |
| SECONDARY Percentage of Participants With HBV DNA <20,000 IU/mL at EOT/POP in Groups A and B |
36.6; 12 | — |
| SECONDARY Percentage of Participants With HBV DNA <2,000 IU/mL at EOT/POP in Groups A and B |
30.7; 2 | — |
| SECONDARY Percentage of Participants With HBV DNA Undetectable at EOT/POP in Groups A and B |
18.8; 0 | — |
| SECONDARY Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at EOT/POP in Groups A and B |
6.9; 6 | — |
| SECONDARY Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at EOT/POP in Groups A and B |
6.9; 0 | — |
| SECONDARY Quantitative Serum ALT Level in Groups A and B |
2.779; 2.878; 3.427; 2.846; 3.343; 3.262 | — |
| SECONDARY Quantitative HBV DNA Level in Groups A and B |
8.094; 8.056; 6.49; 7.909; 5.966; 7.857 | — |
| SECONDARY Change From Baseline in Quantitative HBV DNA Level in Groups A and B |
-1.588; -0.156; -2.112; -0.168; -2.525; -0.359 | — |
| SECONDARY Percentage of Participants With Loss of HBeAg at 24 Weeks After EOT in Group C |
30 | — |
| SECONDARY Percentage of Participants With HBsAg Seroconversion at 24 Weeks After EOT in Group C |
— | — |
| SECONDARY Percentage of Participants With Loss of HBsAg at 24 Weeks After EOT in Group C |
— | — |
| SECONDARY Percentage of Participants With Normal ALT at 24 Weeks After EOT in Group C |
70 | — |
| SECONDARY Percentage of Participants With HBV DNA <20,000 IU/mL at 24 Weeks After EOT in Group C |
70 | — |
| SECONDARY Percentage of Participants With HBV DNA <2,000 IU/mL at 24 Weeks After EOT in Group C |
70 | — |
| SECONDARY Percentage of Participants With HBV DNA Undetectable at 24 Weeks After EOT in Group C |
30 | — |
| SECONDARY Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at 24 Weeks After EOT in Group C |
30 | — |
| SECONDARY Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at 24 Weeks After EOT in Group C |
30 | — |
| SECONDARY Percentage of Participants With HBeAg Seroconversion at EOT in Group C |
20 | — |
| SECONDARY Percentage of Participants With Loss of HBeAg at EOT in Group C |
20 | — |
| SECONDARY Percentage of Participants With HBsAg Seroconversion at EOT in Group C |
— | — |
| SECONDARY Percentage of Participants With Loss of HBsAg at EOT in Group C |
— | — |
| SECONDARY Percentage of Participants With Normal ALT at EOT in Group C |
40 | — |
| SECONDARY Percentage of Participants With HBV DNA <20,000 IU/mL at EOT in Group C |
40 | — |
| SECONDARY Percentage of Participants With HBV DNA <2,000 IU/mL at EOT in Group C |
30 | — |
| SECONDARY Percentage of Participants With HBV DNA Undetectable at EOT in Group C |
20 | — |
| SECONDARY Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at EOT in Group C |
20 | — |
| SECONDARY Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at EOT in Group C |
20 | — |
| SECONDARY Quantitative Serum ALT Level in Group C |
2.804; 3.117; 2.896; 2.444; 2.703; 2.793 | — |
| SECONDARY Quantitative HBV DNA Level in Group C |
7.866; 5.782; 5.599; 5.2; 5.319; 4.604 | — |
| SECONDARY Change From Baseline in Quantitative HBV DNA Level in Group C |
-2.084; -2.267; -2.529; -2.546; -3.262; -3.613 | — |
| SECONDARY Estimated Area Under the Concentration-Time Curve (AUC) by BSA Category |
3320; 4037; 2765; 3448 | — |
| SECONDARY Percentage of Participants With >15% Drop in Height Percentile for Age in Groups A and B |
1; 0; 5; 8.5; 4; 4.2 | — |
| SECONDARY Percentage of Participants With >15% Drop in Weight Percentile for Age in Groups A and B |
2; 5; 5.1; 2.1; 8.1; 16 | — |
| SECONDARY Quantitative HBeAg Level in Groups A and B |
2.736; 2.568; 2.09; 2.391; 1.865; 2.36 | — |
| SECONDARY Quantitative HBsAg Level in Groups A and B |
4.309; 4.383; 3.844; 4.299; 3.509; 4.336 | — |
| SECONDARY Quantitative HBeAg Level in Group C |
2.344; 1.62; 1.802; 1.561; 1.429; 1.442 | — |
| SECONDARY Quantitative HBsAg Level in Group C |
4.225; 3.829; 3.515; 3.282; 3.215; 3.137 | — |
| SECONDARY Change From Baseline in Liver Stiffness Measure (LSM) in Groups A, B, C |
-0.49; 0.376; -1.517; -1.026; -0.72; -1.7 | — |
| SECONDARY Percentage of Participants With >15% Drop in Height Percentile for Age in Group C |
20; 10; 10; 10; 20 | — |
| SECONDARY Change From Baseline in Height for Age Z-Score in Groups A and B |
0.271; -0.062; 0.011; -0.006; -0.04; -0.071 | — |
| SECONDARY Change From Baseline in Weight for Age Z-Score in Groups A and B |
0.106; -0.047; -0.024; -0.023; -0.048; -0.082 | — |
| SECONDARY Change From Baseline in Height for Age Z-Score in Group C |
0.586; 0.07; 0.262; 0.3; 0.19; 0.205 | — |
| SECONDARY Change From Baseline in Weight for Age Z-Score in Group C |
0.187; -0.044; -0.023; 0.049; -0.041; 0.012 | — |
| SECONDARY Percentage of Participants With HBeAg Seroconversion at 24 Weeks After EOT in Group C |
30 | — |
| SECONDARY Change From Baseline in Quantitative Serum ALT Level in Groups A and B |
0.606; 0.06; 0.564; 0.463; 0.415; 0.598 | — |
| SECONDARY Change From Baseline in Quantitative HBeAg Level in Groups A and B |
-0.583; -0.225; -0.834; -0.261; 1.123; -0.3 | — |
| SECONDARY Change From Baseline in Quantitative HBsAg Level in Groups A and B |
-0.444; -0.081; -0.798; -0.032; -1.051; -0.126 | — |
| SECONDARY Change From Baseline in Quantitative Serum ALT Level in Group C |
0.313; 0.091; -0.361; -0.101; -0.012; -0.589 | — |
| SECONDARY Change From Baseline in Quantitative HBeAg Level in Group C |
-0.779; -0.817; -0.817; -0.762; -0.742 | — |
| SECONDARY Change From Baseline in Quantitative HBsAg Level in Group C |
-0.397; -0.71; -0.943; -1.01; -1.088 | — |
| SECONDARY Percentage of Participants With HBeAg Seroconversion Over Time in Groups A and B |
0.00; 0.00; 32.7; 6.08; 33.7; 6.08 | — |
| SECONDARY Percentage of Participants With Loss of HBeAg at 24 Weeks After the End of Switch Treatment Period: Switch Group |
30.3 | — |
| SECONDARY Percentage of Participants With HBsAg Seroconversion at 24 Weeks After the End of Switch Treatment Period: Switch Group |
9.1 | — |
| SECONDARY Percentage of Participants With Loss of HBsAg at 24 Weeks After the End of Switch Treatment Period: Switch Group |
12.1 | — |
| SECONDARY Percentage of Participants With Normal ALT at 24 Weeks After the End of Switch Treatment Period: Switch Group |
42.4 | — |
| SECONDARY Percentage of Participants With HBV Deoxyribonucleic Acid (DNA) <20,000 International Units Per Milliliter (IU/mL) at 24 Weeks After the End of Switch Treatment Period: Switch Group |
36.4 | — |
| SECONDARY Percentage of Participants With HBV DNA <2,000 IU/mL at 24 Weeks After the End of Switch Treatment Period: Switch Group |
27.3 | — |
| SECONDARY Percentage of Participants With HBV DNA Undetectable at 24 Weeks After the End of Switch Treatment Period: Switch Group |
18.2 | — |
| SECONDARY Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <20,000 IU/mL at 24 Weeks After the End of Switch Treatment Period: Switch Group |
27.3 | — |
| SECONDARY Percentage of Participants With Combined HBeAg Seroconversion and HBV DNA <2,000 IU/mL at 24 Weeks After the End of Switch Treatment Period: Switch Group |
21.2 | — |
Summary
This parallel group, open label study will evaluate the safety and efficacy of Pegasys (peginterferon alfa-2a) versus untreated control in children (age 3 years to <18 years at baseline) with HBeAg positive chronic hepatitis B. Children without advanced fibrosis and without cirrhosis will be randomized 2:1 to treatment Group A, receiving Pegasys 45-180 mcg subcutaneously weekly for 48 weeks, or to the untreated control Group B. Children with advanced fibrosis will be assigned to treatment group C and receive 48 weeks of treatment with Pegasys. Children in the untreated control Group B who have not experienced seroconversion 48 weeks after randomization may enter the Switch Arm to receive 48 weeks of Pegasys treatment. This offer will be available for 1 year following 48 weeks from randomization. Anticipated time on study treatment is 48 weeks. All subjects will be followed up for 5 years after the end of treatment (A,C,Switch)/principal observation (B) period.
Eligibility Criteria
Inclusion Criteria
- Male or female patients, 3 years to <18 years of age at baseline
- Positive HBsAg for more than 6 months
- Positive HBeAg and detectable HBV DNA at screening
- A liver biopsy obtained within the past 2 years prior to baseline (and more than 6 months after the end of previous therapy for hepatitis B) to confirm the presence of advanced fibrosis or exclude cirrhosis
- Compensated liver disease (Child-Pugh Class A)
- Elevated serum alanine transferase (ALT)
- Normal thyroid gland function at screening
Exclusion Criteria
- Subjects with cirrhosis
- Subjects must not have received investigational drugs or licensed treatments with anti-HBV activity within 6 months of baseline. Subjects who are expected to need systemic antiviral therapy other than that provided by the study at any time during their participation in the study are also excluded
- Known hypersensitivity to peginterferon
- Positive test results at screening for hepatitis A, hepatitis C, hepatitis D or HIV infection
- History or evidence of medical condition associated with chronic liver disease other than chronic hepatitis B
- History or evidence of bleeding from esophageal varices
- Decompensated liver disease (e.g. ascites, Child-Pugh Class B or C)
- History of immunologically mediated disease
- Pregnant or lactating females
Data sourced from ClinicalTrials.gov (NCT01519960). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.