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NCT02364336

Add-on Peginterferon Following Nucleos(t)Ide Analogue Treatment

Completed Phase 2 Results posted Last updated 4 September 2019
What this trial tests

Phase 2 trial testing Peginterferon alfa-2a in Chronic Hepatitis B in 14 participants. Completed in 21 May 2018.

Timeline
14 February 2015
Primary endpoint
21 May 2018
21 May 2018

Quick facts

Lead sponsorNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment14
Start date14 February 2015
Primary completion21 May 2018
Estimated completion21 May 2018
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Who can join

Adults 18 to 80, any sex, with Chronic Hepatitis B. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Interferon-stimulated-gene (ISG) Expression Primary · 6 hours after first injection of peginterferon

Change in level of ISG expression before and after 1st peginterferon injection

PPP1R3G
GroupValue95% CI
HBeAg Negative-2.716± 0.628
ALAS1
GroupValue95% CI
HBeAg Negative1.670± 0.416
INHBB
GroupValue95% CI
HBeAg Negative-2.20± 0.570
MMRN1
GroupValue95% CI
HBeAg Negative-1.597± 0.432
LYVE1
GroupValue95% CI
HBeAg Negative-1.184± 0.326
SLC8A1
GroupValue95% CI
HBeAg Negative-1.382± 0.386
PPARGC1A
GroupValue95% CI
HBeAg Negative-1.573± 0.443
NOTUM
GroupValue95% CI
HBeAg Negative0.870± 0.250
Hepatitis B e Antigen (HBeAg) Loss Secondary · End of treatment, 24 weeks, and 48 weeks

Proportion of HBeAg positive patients showing eAg loss at end of treatment, and 24 and 48 weeks off peginterferon treatment.

End of treatment
GroupValue95% CI
HBeAg Positive0
Week 24 post treatment
GroupValue95% CI
HBeAg Positive0
Week 48 post treatment
GroupValue95% CI
HBeAg Positive0
Hepatitis B s Antigen (HBsAg) Loss Secondary · End of treatment, 24 weeks, and 48 weeks

Proportion of HBsAg positive patients showing sAG loss at end of treatment and 24 and 48 weeks off peginterferon treatment

End of treatment
GroupValue95% CI
HBeAg Positive0
HBeAg Negative1
Week 24 post treatment
GroupValue95% CI
HBeAg Positive0
HBeAg Negative0
Week 48 post treatment
GroupValue95% CI
HBeAg Positive0
HBeAg Negative0
Change in Natural Killer (NK) Cell Frequency Secondary · 6 hours after first injection of peginterferon and baseline

NK cell frequency is calculated as 100\*(NK cells)/(mononuclear cells). Changes are calculated by subtracting baseline from 6 hours after first peginterferon injection.

Blood baseline
GroupValue95% CI
HBeAg Positive15.60± NA
HBeAg Negative11.82± 10.19
Blood 6 hours
GroupValue95% CI
HBeAg Positive10.30± NA
HBeAg Negative13.74± 10.68
Blood change
GroupValue95% CI
HBeAg Positive-5.3± NA
HBeAg Negative1.92± 7.48
Liver baseline
GroupValue95% CI
HBeAg Negative24.69± 6.26
Liver 6 hours
GroupValue95% CI
HBeAg Negative24.78± 7.28
Liver change
GroupValue95% CI
HBeAg Negative0.09± 4.08
Change in Natural Killer (NK) Cell Degranulation Secondary · 6 hours after first injection of peginterferon and baseline

NK cell degranulation is calculated as 100\*(degranulated NK cells)/(NK cells). Changes are calculated by subtracting baseline from 6 hours after first peginterferon injection.

Blood baseline
GroupValue95% CI
HBeAg Positive0.08± NA
HBeAg Negative0.64± 0.65
Blood 6 hours
GroupValue95% CI
HBeAg Positive0.06± NA
HBeAg Negative0.52± 0.66
Blood change
GroupValue95% CI
HBeAg Positive-0.02± NA
HBeAg Negative-0.12± 0.93
Liver baseline
GroupValue95% CI
HBeAg Negative3.37± 1.46
Liver 6 hours
GroupValue95% CI
HBeAg Negative4.87± 4.47
Liver change
GroupValue95% CI
HBeAg Negative1.51± 5.08

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse event data were collected over three periods encompassing a total of 50 to 60 weeks. The first period was up to twelve weeks, from pre-treatment biopsy to start of peginterferon treatment. The second period was 24 weeks during treatment with peginterferon, and the third period was after completion of treatment with peginterferon.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

HBeAg Positive
Serious: 0/1 (0%)
Deaths: 0/1
HBeAg Negative
Serious: 1/12 (8%)
Deaths: 0/12

Serious adverse events (1 terms)

ReactionSystemHBeAg PositiveHBeAg Negative
SepsisInfections and infestations
Other adverse events (34 terms — click to expand)

ReactionSystemHBeAg PositiveHBeAg Negative
FatigueGeneral disorders
headacheNervous system disorders
myalgiaMusculoskeletal and connective tissue disorders
AnorexiaGastrointestinal disorders
insomniaPsychiatric disorders
PruritisSkin and subcutaneous tissue disorders
DizzinessNervous system disorders
Dry MouthGastrointestinal disorders
Dry SkinSkin and subcutaneous tissue disorders
Weight lossInvestigations
AnxietyPsychiatric disorders
ChillsGeneral disorders
CoughRespiratory, thoracic and mediastinal disorders
Urinary frequencyRenal and urinary disorders
melancholyPsychiatric disorders
Back PainMusculoskeletal and connective tissue disorders
irritabilityPsychiatric disorders
joint painMusculoskeletal and connective tissue disorders
nauseaGastrointestinal disorders
Abdominal PainGastrointestinal disorders
Blurred VisionEye disorders
DiarrheaGastrointestinal disorders
FeverGeneral disorders
hair lossSkin and subcutaneous tissue disorders
Biopsy Site PainInjury, poisoning and procedural complications
ConstipationGastrointestinal disorders
Fast or pounding heartbeatCardiac disorders
rashSkin and subcutaneous tissue disorders
shortness of breathRespiratory, thoracic and mediastinal disorders
infectionInfections and infestations
irritation at injection siteInjury, poisoning and procedural complications
toothacheGastrointestinal disorders
VomitingGastrointestinal disorders
IndigestionGastrointestinal disorders

Most-reported serious reactions: Sepsis.

Data from ClinicalTrials.gov NCT02364336 adverse events section.

Sponsor's own description

Background: \- Chronic hepatitis B is caused by a virus that infects the liver. Cure is not possible but the virus can be controlled with the use of antiviral medicines,. Researchers think that adding a second antiviral medicine might help. Objective: \- To understand how peginterferon might help treat people with chronic hepatitis B. Also, to see if peginterferon is safe to use with other antiviral medications. Eligibility: \- Adults age 18 and older who have chronic hepatitis B and had therapy with 1 or more oral medicines for hepatitis B for at least 4 years. Design: * Participants will be screened with physical exam and medical history. They will complete health questionnaires about their levels of fatigue and pain. They will have blood and urine tests. They may have an eye exam. * Participants also will have a Fibroscan. A test to measure how stiff your liver is. * Eligible participants will have a liver biopsy. Blood will be drawn. * Participants will be admitted to the NIH Clinical Center. They will be injected with the study drug. Then they will have a second liver biopsy. They will be discharged 24 hours later. * Participants will give themselves study drug injections under the skin weekly for 24 weeks. * Participants will have 5 clinic visits during the 24-week treatment period. Then they will have follow-up visits every 12 weeks for 48 weeks. * During visits, participants may have a physical exam and medical history. They may have blood and urine tests. They may have a Fibroscan and complete questionnaires. At the final visit, they will also have a Fibroscan.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Clearance of pegylated interferon by Kupffer cells limits NK cell activation and therapy response of patients with HBV infection.
    Nishio A, Bolte FJ, Takeda K, Park N, et al · · 2021 · cited 42× · PMID 33790025 · DOI 10.1126/scitranslmed.aba6322
  2. Long-term lamivudine therapy in chronic hepatitis B.
    Lingala S, Lau DT, Koh C, Auh S, et al · · 2016 · cited 11× · PMID 27375283 · DOI 10.1111/apt.13707

Verify or expand the search:

Other trials of Peginterferon alfa-2a

Trials testing the same drug.

Other recruiting trials for Chronic Hepatitis B

Currently open trials in the same condition.

Other National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing