Trial Outcomes & Findings for Peg-interferon ADDed to an Ongoing Nucleos(t)Ide Based Treatment in Patients With Chronic Hepatitis B to Induce Decrease of HBs-Antigen (NCT NCT01524679)
NCT ID: NCT01524679
Last Updated: 2020-02-18
Results Overview
Difference in percentage of patients between treatment and comparator arm reaching a ≥ 1log10 decline (tenfold reduction) of quantitative HBsAg after 48 weeks
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
170 participants
Primary outcome timeframe
48 weeks
Results posted on
2020-02-18
Participant Flow
Participant milestones
| Measure |
Treatment Group
pegylated interferon alfa-2a (Pegasys®) 180 μg once weekly for 48 weeks added to an ongoing nucleos(t)ide based treatment in patients with chronic HBeAg-negative hepatitis B
Pegylated interferon alfa-2a plus nucleos(t)ide(s): Pegylated interferon alfa-2a, s.c. 180 μg 1x/wk in addition to nucleos(t)ide(s)
|
Control Group
ongoing nucleos(t)ide based treatment alone
|
|---|---|---|
|
Overall Study
STARTED
|
112
|
58
|
|
Overall Study
COMPLETED
|
89
|
49
|
|
Overall Study
NOT COMPLETED
|
23
|
9
|
Reasons for withdrawal
| Measure |
Treatment Group
pegylated interferon alfa-2a (Pegasys®) 180 μg once weekly for 48 weeks added to an ongoing nucleos(t)ide based treatment in patients with chronic HBeAg-negative hepatitis B
Pegylated interferon alfa-2a plus nucleos(t)ide(s): Pegylated interferon alfa-2a, s.c. 180 μg 1x/wk in addition to nucleos(t)ide(s)
|
Control Group
ongoing nucleos(t)ide based treatment alone
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
4
|
|
Overall Study
Withdrawal by Subject
|
4
|
4
|
|
Overall Study
Adverse Event
|
9
|
0
|
|
Overall Study
Protocol Violation
|
1
|
0
|
|
Overall Study
Lack of Efficacy
|
2
|
0
|
|
Overall Study
e.g.wish for children, relocation
|
6
|
1
|
Baseline Characteristics
Measure was not determined by the laboratory in 3 cases.
Baseline characteristics by cohort
| Measure |
Treatment Group
n=110 Participants
pegylated interferon alfa-2a (Pegasys®) 180 μg once weekly for 48 weeks added to an ongoing nucleos(t)ide based treatment in patients with chronic HBeAg-negative hepatitis B
Pegylated interferon alfa-2a plus nucleos(t)ide(s): Pegylated interferon alfa-2a, s.c. 180 μg 1x/wk in addition to nucleos(t)ide(s)
|
Control Group
n=55 Participants
ongoing nucleos(t)ide based treatment alone
|
Total
n=165 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
43.8 years
STANDARD_DEVIATION 9.6 • n=110 Participants
|
45.1 years
STANDARD_DEVIATION 9.7 • n=55 Participants
|
44.3 years
STANDARD_DEVIATION 9.6 • n=165 Participants
|
|
Sex: Female, Male
Female
|
26 Participants
n=110 Participants
|
16 Participants
n=55 Participants
|
42 Participants
n=165 Participants
|
|
Sex: Female, Male
Male
|
84 Participants
n=110 Participants
|
39 Participants
n=55 Participants
|
123 Participants
n=165 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=110 Participants
|
0 Participants
n=55 Participants
|
0 Participants
n=165 Participants
|
|
Race (NIH/OMB)
Asian
|
15 Participants
n=110 Participants
|
6 Participants
n=55 Participants
|
21 Participants
n=165 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=110 Participants
|
0 Participants
n=55 Participants
|
0 Participants
n=165 Participants
|
|
Race (NIH/OMB)
Black or African American
|
7 Participants
n=110 Participants
|
6 Participants
n=55 Participants
|
13 Participants
n=165 Participants
|
|
Race (NIH/OMB)
White
|
85 Participants
n=110 Participants
|
39 Participants
n=55 Participants
|
124 Participants
n=165 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=110 Participants
|
0 Participants
n=55 Participants
|
0 Participants
n=165 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=110 Participants
|
4 Participants
n=55 Participants
|
7 Participants
n=165 Participants
|
|
Region of Enrollment
Germany
|
110 participants
n=110 Participants
|
55 participants
n=55 Participants
|
165 participants
n=165 Participants
|
|
Virology: HBV DNA quant. negative?
Yes
|
109 Participants
n=110 Participants
|
54 Participants
n=55 Participants
|
163 Participants
n=165 Participants
|
|
Virology: HBV DNA quant. negative?
No
|
1 Participants
n=110 Participants
|
1 Participants
n=55 Participants
|
2 Participants
n=165 Participants
|
|
Virology: Anti-HBs
Positive
|
7 Participants
n=110 Participants
|
2 Participants
n=55 Participants
|
9 Participants
n=165 Participants
|
|
Virology: Anti-HBs
Negative
|
103 Participants
n=110 Participants
|
53 Participants
n=55 Participants
|
156 Participants
n=165 Participants
|
|
Virology: HBeAg
Positive
|
0 Participants
n=110 Participants
|
0 Participants
n=55 Participants
|
0 Participants
n=165 Participants
|
|
Virology: HBeAg
Negative
|
110 Participants
n=110 Participants
|
55 Participants
n=55 Participants
|
165 Participants
n=165 Participants
|
|
Virology: Anti-HBe
Positive
|
96 Participants
n=107 Participants • Measure was not determined by the laboratory in 3 cases.
|
45 Participants
n=55 Participants • Measure was not determined by the laboratory in 3 cases.
|
141 Participants
n=162 Participants • Measure was not determined by the laboratory in 3 cases.
|
|
Virology: Anti-HBe
Negative
|
11 Participants
n=107 Participants • Measure was not determined by the laboratory in 3 cases.
|
10 Participants
n=55 Participants • Measure was not determined by the laboratory in 3 cases.
|
21 Participants
n=162 Participants • Measure was not determined by the laboratory in 3 cases.
|
|
Virology: Anti-HBc
Positive
|
94 Participants
n=109 Participants • Measure was not determined by the laboratory in one case.
|
48 Participants
n=55 Participants • Measure was not determined by the laboratory in one case.
|
142 Participants
n=164 Participants • Measure was not determined by the laboratory in one case.
|
|
Virology: Anti-HBc
Negative
|
15 Participants
n=109 Participants • Measure was not determined by the laboratory in one case.
|
7 Participants
n=55 Participants • Measure was not determined by the laboratory in one case.
|
22 Participants
n=164 Participants • Measure was not determined by the laboratory in one case.
|
|
Virology: HCV
Positive
|
0 Participants
n=110 Participants
|
0 Participants
n=55 Participants
|
0 Participants
n=165 Participants
|
|
Virology: HCV
Negative
|
110 Participants
n=110 Participants
|
55 Participants
n=55 Participants
|
165 Participants
n=165 Participants
|
|
Virology: HDV
Positive
|
0 Participants
n=110 Participants
|
0 Participants
n=55 Participants
|
0 Participants
n=165 Participants
|
|
Virology: HDV
Negative
|
110 Participants
n=110 Participants
|
55 Participants
n=55 Participants
|
165 Participants
n=165 Participants
|
|
Virology: HIV
Positive
|
0 Participants
n=109 Participants • Measure was not determined by the laboratory in one case.
|
0 Participants
n=55 Participants • Measure was not determined by the laboratory in one case.
|
0 Participants
n=164 Participants • Measure was not determined by the laboratory in one case.
|
|
Virology: HIV
Negative
|
109 Participants
n=109 Participants • Measure was not determined by the laboratory in one case.
|
55 Participants
n=55 Participants • Measure was not determined by the laboratory in one case.
|
164 Participants
n=164 Participants • Measure was not determined by the laboratory in one case.
|
|
HBV Genotype known?
Yes
|
22 Participants
n=110 Participants
|
12 Participants
n=55 Participants
|
34 Participants
n=165 Participants
|
|
HBV Genotype known?
No
|
88 Participants
n=110 Participants
|
43 Participants
n=55 Participants
|
131 Participants
n=165 Participants
|
|
HBV Genotype
Genotype A
|
2 Participants
n=22 Participants • The Genotype was only available in 34 patients.
|
1 Participants
n=12 Participants • The Genotype was only available in 34 patients.
|
3 Participants
n=34 Participants • The Genotype was only available in 34 patients.
|
|
HBV Genotype
Genotype C
|
1 Participants
n=22 Participants • The Genotype was only available in 34 patients.
|
0 Participants
n=12 Participants • The Genotype was only available in 34 patients.
|
1 Participants
n=34 Participants • The Genotype was only available in 34 patients.
|
|
HBV Genotype
Genotype D
|
16 Participants
n=22 Participants • The Genotype was only available in 34 patients.
|
11 Participants
n=12 Participants • The Genotype was only available in 34 patients.
|
27 Participants
n=34 Participants • The Genotype was only available in 34 patients.
|
|
HBV Genotype
Genotype E
|
1 Participants
n=22 Participants • The Genotype was only available in 34 patients.
|
0 Participants
n=12 Participants • The Genotype was only available in 34 patients.
|
1 Participants
n=34 Participants • The Genotype was only available in 34 patients.
|
|
HBV Genotype
Wildtype
|
1 Participants
n=22 Participants • The Genotype was only available in 34 patients.
|
0 Participants
n=12 Participants • The Genotype was only available in 34 patients.
|
1 Participants
n=34 Participants • The Genotype was only available in 34 patients.
|
|
HBV Genotype
Not specified
|
1 Participants
n=22 Participants • The Genotype was only available in 34 patients.
|
0 Participants
n=12 Participants • The Genotype was only available in 34 patients.
|
1 Participants
n=34 Participants • The Genotype was only available in 34 patients.
|
|
HBsAG Concentration
|
6547.5 IU/mL
STANDARD_DEVIATION 10326.2 • n=107 Participants • HBsAG was not determined by the laboratory in 4 patients.
|
8434.9 IU/mL
STANDARD_DEVIATION 12660.1 • n=54 Participants • HBsAG was not determined by the laboratory in 4 patients.
|
7180.6 IU/mL
STANDARD_DEVIATION 11159.5 • n=161 Participants • HBsAG was not determined by the laboratory in 4 patients.
|
PRIMARY outcome
Timeframe: 48 weeksPopulation: mITT population consisting of all randomized patients with at least one post-baseline measurement
Difference in percentage of patients between treatment and comparator arm reaching a ≥ 1log10 decline (tenfold reduction) of quantitative HBsAg after 48 weeks
Outcome measures
| Measure |
Treatment Group
n=106 Participants
pegylated interferon alfa-2a (Pegasys®) 180 μg once weekly for 48 weeks added to an ongoing nucleos(t)ide based treatment in patients with chronic HBeAg-negative hepatitis B
Pegylated interferon alfa-2a plus nucleos(t)ide(s): Pegylated interferon alfa-2a, s.c. 180 μg 1x/wk in addition to nucleos(t)ide(s)
|
Control Group
n=54 Participants
ongoing nucleos(t)ide based treatment alone
|
|---|---|---|
|
Difference in Percentage of Patients Between Treatment and Comparator Arm Reaching a ≥ 1log10 Decline of Quantitative HBsAg After 48 Weeks
Yes
|
26 Participants
|
1 Participants
|
|
Difference in Percentage of Patients Between Treatment and Comparator Arm Reaching a ≥ 1log10 Decline of Quantitative HBsAg After 48 Weeks
Missing
|
80 Participants
|
53 Participants
|
SECONDARY outcome
Timeframe: week 12Population: Values were only available in 154 patients.
Change in quantitative HBs antigen at week 12. The data were log transformed before analysis and the changes to baseline were analysed. Therefore, the reported values might be interpreted as percentage changes. Lower scores mean a better outcome.
Outcome measures
| Measure |
Treatment Group
n=101 Participants
pegylated interferon alfa-2a (Pegasys®) 180 μg once weekly for 48 weeks added to an ongoing nucleos(t)ide based treatment in patients with chronic HBeAg-negative hepatitis B
Pegylated interferon alfa-2a plus nucleos(t)ide(s): Pegylated interferon alfa-2a, s.c. 180 μg 1x/wk in addition to nucleos(t)ide(s)
|
Control Group
n=53 Participants
ongoing nucleos(t)ide based treatment alone
|
|---|---|---|
|
Change in Quantitative HBs Antigen at Week 12
|
0.7058 IU/ml
Interval 0.5803 to 0.8585
|
0.9380 IU/ml
Interval 0.7154 to 1.2297
|
SECONDARY outcome
Timeframe: week 24Population: Values were only available in 151 patients.
Change in quantitative HBs antigen at week 24. The data were log transformed before analysis and the changes to baseline were analysed. Therefore, the reported values might be interpreted as percentage changes. Lower scores mean a better outcome.
Outcome measures
| Measure |
Treatment Group
n=99 Participants
pegylated interferon alfa-2a (Pegasys®) 180 μg once weekly for 48 weeks added to an ongoing nucleos(t)ide based treatment in patients with chronic HBeAg-negative hepatitis B
Pegylated interferon alfa-2a plus nucleos(t)ide(s): Pegylated interferon alfa-2a, s.c. 180 μg 1x/wk in addition to nucleos(t)ide(s)
|
Control Group
n=52 Participants
ongoing nucleos(t)ide based treatment alone
|
|---|---|---|
|
Change in Quantitative HBs Antigen at Week 24
|
0.3694 IU/ml
Interval 0.2872 to 0.4752
|
0.7995 IU/ml
Interval 0.5646 to 1.1322
|
Adverse Events
Treatment Group
Serious events: 13 serious events
Other events: 106 other events
Deaths: 0 deaths
Control Group
Serious events: 4 serious events
Other events: 20 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Treatment Group
n=112 participants at risk
pegylated interferon alfa-2a (Pegasys®) 180 μg once weekly for 48 weeks added to an ongoing nucleos(t)ide based treatment in patients with chronic HBeAg-negative hepatitis B
Pegylated interferon alfa-2a plus nucleos(t)ide(s): Pegylated interferon alfa-2a, s.c. 180 μg 1x/wk in addition to nucleos(t)ide(s)
|
Control Group
n=58 participants at risk
ongoing nucleos(t)ide based treatment alone
|
|---|---|---|
|
Injury, poisoning and procedural complications
Contusion
|
0.89%
1/112 • Number of events 1 • 48 weeks
|
0.00%
0/58 • 48 weeks
|
|
Cardiac disorders
Aortic valve stenosis
|
0.89%
1/112 • Number of events 1 • 48 weeks
|
0.00%
0/58 • 48 weeks
|
|
Injury, poisoning and procedural complications
Meniscus injury
|
0.89%
1/112 • Number of events 1 • 48 weeks
|
0.00%
0/58 • 48 weeks
|
|
Injury, poisoning and procedural complications
forearm fracture
|
0.89%
1/112 • Number of events 1 • 48 weeks
|
0.00%
0/58 • 48 weeks
|
|
Injury, poisoning and procedural complications
facial bones fracture
|
0.89%
1/112 • Number of events 1 • 48 weeks
|
0.00%
0/58 • 48 weeks
|
|
Eye disorders
retinal haemorrhage
|
0.89%
1/112 • Number of events 1 • 48 weeks
|
0.00%
0/58 • 48 weeks
|
|
Surgical and medical procedures
internal fixation of fracture
|
0.89%
1/112 • Number of events 1 • 48 weeks
|
0.00%
0/58 • 48 weeks
|
|
Cardiac disorders
coronary artery disease
|
0.89%
1/112 • Number of events 1 • 48 weeks
|
0.00%
0/58 • 48 weeks
|
|
Renal and urinary disorders
renal colic
|
0.89%
1/112 • Number of events 1 • 48 weeks
|
0.00%
0/58 • 48 weeks
|
|
Infections and infestations
chlamydial infection
|
0.89%
1/112 • Number of events 1 • 48 weeks
|
0.00%
0/58 • 48 weeks
|
|
Endocrine disorders
hyperthyroidism
|
0.89%
1/112 • Number of events 1 • 48 weeks
|
0.00%
0/58 • 48 weeks
|
|
Blood and lymphatic system disorders
lymphadenopathy
|
0.89%
1/112 • Number of events 1 • 48 weeks
|
0.00%
0/58 • 48 weeks
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
hepatocellular lymphoma
|
0.89%
1/112 • Number of events 1 • 48 weeks
|
0.00%
0/58 • 48 weeks
|
|
Musculoskeletal and connective tissue disorders
arthralgia
|
0.89%
1/112 • Number of events 1 • 48 weeks
|
0.00%
0/58 • 48 weeks
|
|
Musculoskeletal and connective tissue disorders
osteoarthritis
|
0.89%
1/112 • Number of events 1 • 48 weeks
|
0.00%
0/58 • 48 weeks
|
|
General disorders
pain
|
0.89%
1/112 • Number of events 1 • 48 weeks
|
0.00%
0/58 • 48 weeks
|
|
Infections and infestations
pyelonephritis
|
0.00%
0/112 • 48 weeks
|
1.7%
1/58 • Number of events 1 • 48 weeks
|
|
Infections and infestations
urinary tract infection
|
0.00%
0/112 • 48 weeks
|
1.7%
1/58 • Number of events 1 • 48 weeks
|
|
Musculoskeletal and connective tissue disorders
foot deformity
|
0.00%
0/112 • 48 weeks
|
1.7%
1/58 • Number of events 1 • 48 weeks
|
|
Reproductive system and breast disorders
endometrial hyperplasia
|
0.00%
0/112 • 48 weeks
|
1.7%
1/58 • Number of events 1 • 48 weeks
|
|
Reproductive system and breast disorders
vaginal haemorrhage
|
0.00%
0/112 • 48 weeks
|
1.7%
1/58 • Number of events 1 • 48 weeks
|
|
Respiratory, thoracic and mediastinal disorders
nasal tubinate hypertrophy
|
0.00%
0/112 • 48 weeks
|
1.7%
1/58 • Number of events 1 • 48 weeks
|
|
Skin and subcutaneous tissue disorders
skin hyperpigmentation
|
0.00%
0/112 • 48 weeks
|
1.7%
1/58 • Number of events 1 • 48 weeks
|
Other adverse events
| Measure |
Treatment Group
n=112 participants at risk
pegylated interferon alfa-2a (Pegasys®) 180 μg once weekly for 48 weeks added to an ongoing nucleos(t)ide based treatment in patients with chronic HBeAg-negative hepatitis B
Pegylated interferon alfa-2a plus nucleos(t)ide(s): Pegylated interferon alfa-2a, s.c. 180 μg 1x/wk in addition to nucleos(t)ide(s)
|
Control Group
n=58 participants at risk
ongoing nucleos(t)ide based treatment alone
|
|---|---|---|
|
General disorders
chills
|
9.8%
11/112 • Number of events 19 • 48 weeks
|
0.00%
0/58 • 48 weeks
|
|
General disorders
fatigue
|
42.9%
48/112 • Number of events 52 • 48 weeks
|
3.4%
2/58 • Number of events 2 • 48 weeks
|
|
General disorders
influenza like illness
|
11.6%
13/112 • Number of events 21 • 48 weeks
|
3.4%
2/58 • Number of events 2 • 48 weeks
|
|
General disorders
injection site erythema
|
9.8%
11/112 • Number of events 12 • 48 weeks
|
0.00%
0/58 • 48 weeks
|
|
General disorders
pyrexia
|
22.3%
25/112 • Number of events 28 • 48 weeks
|
0.00%
0/58 • 48 weeks
|
|
Musculoskeletal and connective tissue disorders
arthralgia
|
27.7%
31/112 • Number of events 45 • 48 weeks
|
0.00%
0/58 • 48 weeks
|
|
Musculoskeletal and connective tissue disorders
back pain
|
13.4%
15/112 • Number of events 17 • 48 weeks
|
3.4%
2/58 • Number of events 3 • 48 weeks
|
|
Musculoskeletal and connective tissue disorders
myalgia
|
17.0%
19/112 • Number of events 21 • 48 weeks
|
0.00%
0/58 • 48 weeks
|
|
Infections and infestations
nasopharyngitis
|
25.0%
28/112 • Number of events 31 • 48 weeks
|
5.2%
3/58 • Number of events 3 • 48 weeks
|
|
Gastrointestinal disorders
abdominal pain upper
|
9.8%
11/112 • Number of events 11 • 48 weeks
|
10.3%
6/58 • Number of events 10 • 48 weeks
|
|
Gastrointestinal disorders
diarrhoea
|
8.0%
9/112 • Number of events 12 • 48 weeks
|
1.7%
1/58 • Number of events 1 • 48 weeks
|
|
Gastrointestinal disorders
nausea
|
10.7%
12/112 • Number of events 13 • 48 weeks
|
1.7%
1/58 • Number of events 1 • 48 weeks
|
|
Nervous system disorders
dizziness
|
9.8%
11/112 • Number of events 18 • 48 weeks
|
0.00%
0/58 • 48 weeks
|
|
Nervous system disorders
headache
|
35.7%
40/112 • Number of events 48 • 48 weeks
|
0.00%
0/58 • 48 weeks
|
|
Skin and subcutaneous tissue disorders
alopecia
|
15.2%
17/112 • Number of events 17 • 48 weeks
|
0.00%
0/58 • 48 weeks
|
|
Skin and subcutaneous tissue disorders
dry skin
|
6.2%
7/112 • Number of events 7 • 48 weeks
|
0.00%
0/58 • 48 weeks
|
|
Skin and subcutaneous tissue disorders
pruritus
|
13.4%
15/112 • Number of events 17 • 48 weeks
|
0.00%
0/58 • 48 weeks
|
|
Skin and subcutaneous tissue disorders
rash
|
7.1%
8/112 • Number of events 10 • 48 weeks
|
0.00%
0/58 • 48 weeks
|
|
Psychiatric disorders
insomnia
|
8.0%
9/112 • Number of events 10 • 48 weeks
|
0.00%
0/58 • 48 weeks
|
|
Respiratory, thoracic and mediastinal disorders
cough
|
8.0%
9/112 • Number of events 10 • 48 weeks
|
3.4%
2/58 • Number of events 2 • 48 weeks
|
|
Respiratory, thoracic and mediastinal disorders
oropharyngeal pain
|
6.2%
7/112 • Number of events 8 • 48 weeks
|
0.00%
0/58 • 48 weeks
|
|
Investigations
transaminases increased
|
5.4%
6/112 • Number of events 9 • 48 weeks
|
0.00%
0/58 • 48 weeks
|
|
Investigations
weight decreased
|
7.1%
8/112 • Number of events 8 • 48 weeks
|
1.7%
1/58 • Number of events 1 • 48 weeks
|
|
Blood and lymphatic system disorders
thrombocytopenia
|
7.1%
8/112 • Number of events 11 • 48 weeks
|
0.00%
0/58 • 48 weeks
|
|
Metabolism and nutrition disorders
decreased appetite
|
5.4%
6/112 • Number of events 9 • 48 weeks
|
0.00%
0/58 • 48 weeks
|
|
Reproductive system and breast disorders
erectile dysfunction
|
5.4%
6/112 • Number of events 6 • 48 weeks
|
0.00%
0/58 • 48 weeks
|
Additional Information
Christian Ruckes
IZKS of the University Medical Center of the Johannes Gutenberg University Mainz
Phone: +49 6131 17
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place