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NCT03905655

Study of Nitazoxanide Compared to Placebo in Subjects With HBeAG-Negative Chronic Hepatitis B

Completed Phase 2 Results posted Last updated 7 November 2023
What this trial tests

Phase 2 trial testing Placebo Oral Tablet in Chronic Hepatitis B in 51 participants. Completed in 11 October 2021.

Timeline
22 October 2019
Primary endpoint
10 March 2021
11 October 2021

Quick facts

Lead sponsorRomark Laboratories L.C.
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment51
Start date22 October 2019
Primary completion10 March 2021
Estimated completion11 October 2021
Sites1 location across Singapore

Drugs / interventions tested

Conditions studied

Sponsor

Romark Laboratories L.C. — full company profile →

Who can join

Adults 21 to 100, 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.

Mean Change in Quantitative Hepatitis B Surface Antigen (qHBsAg) Primary · Baseline to 12 weeks

Mean change in quantitative Hepatitis B Surface Antigen (qHBsAg) from Baseline

GroupValue95% CI
Group 10.0± 0.13
Group 20.0± 0.90
Group 30.0± 0.06
Group 40.0± 0.10
Sustained HBsAg Loss With Suppression of HBV DNA for 24 Weeks After the End of Treatment Secondary · Baseline to 24 weeks after the end of treatment

Proportion of participants with sustained HBsAg loss with suppression of HBV DNA for 24 weeks after the end of treatment

GroupValue95% CI
Group 10
Group 20
Group 30
Group 40
Change in Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline to Different Time Points on Treatment Secondary · 8 weeks

Change in mean Quantitative Hepatitis B Surface Antigen (qHBsAg) from Baseline to Day 3, Week 1, Week 2, Week 4, and Week 8

Day 3
GroupValue95% CI
Group 10.0± 0.04
Group 20.0± 0.08
Group 30.0± 0.04
Group 40.0± 0.06
Week 1
GroupValue95% CI
Group 10.0± 0.06
Group 20.0± 0.05
Group 30.0± 0.04
Group 40.0± 0.05
Week 2
GroupValue95% CI
Group 10.0± 0.05
Group 20.0± 0.11
Group 30.0± 0.04
Group 40.1± 0.05
Week 4
GroupValue95% CI
Group 10.0± 0.08
Group 20.0± 0.09
Group 30.0± 0.05
Group 40.1± 0.07
Week 8
GroupValue95% CI
Group 10.0± 0.06
Group 20.0± 0.14
Group 3-0.1± 0.07
Group 40.0± 0.10
Hepatitis B Surface Antigen (HBsAg) Loss Secondary · 12 weeks

Proportion of participants with HBsAg loss defined as quantitative HBsAg below the lower limit of quantitation at Day 3, Week 1, Week 2, Week 4, Week 8, and Week 12

Day 3
GroupValue95% CI
Group 10
Group 20
Group 30
Group 40
Week 1
GroupValue95% CI
Group 10
Group 20
Group 30
Group 40
Week 2
GroupValue95% CI
Group 10
Group 20
Group 30
Group 40
Week 4
GroupValue95% CI
Group 10
Group 20
Group 30
Group 40
Week 8
GroupValue95% CI
Group 10
Group 20
Group 30
Group 40
Week 12
GroupValue95% CI
Group 10
Group 20
Group 30
Group 40
Hepatitis B Surface Antigen (HBsAg) Seroconversion Secondary · 12 weeks

Proportion of participants with hepatitis B surface antigen (HBsAg) seroconversion defined as HBsAg loss and gain of anti-hepatitis B antibodies at Day 3, Week 1, Week 2, Week 4, Week 8, and Week 12

Day 3
GroupValue95% CI
Group 10
Group 20
Group 30
Group 40
Week 1
GroupValue95% CI
Group 10
Group 20
Group 30
Group 40
Week 2
GroupValue95% CI
Group 10
Group 20
Group 30
Group 40
Week 4
GroupValue95% CI
Group 10
Group 20
Group 30
Group 40
Week 8
GroupValue95% CI
Group 10
Group 20
Group 30
Group 40
Week 12
GroupValue95% CI
Group 10
Group 20
Group 30
Group 40
Hepatitis B Virus DNA Suppression Secondary · 12 weeks

Proportion of participants with hepatitis B virus DNA suppression defined as hepatitis B virus DNA below the lower limit of quantitation (20 IU/mL) at Day 3, Week 1, Week 2, Week 4, Week 8, and Week 12

Day 3
GroupValue95% CI
Group 113
Group 213
Group 311
Group 413
Week 1
GroupValue95% CI
Group 113
Group 212
Group 311
Group 414
Week 2
GroupValue95% CI
Group 113
Group 212
Group 311
Group 413
Week 4
GroupValue95% CI
Group 113
Group 212
Group 311
Group 413
Week 8
GroupValue95% CI
Group 113
Group 212
Group 311
Group 414
Week 12
GroupValue95% CI
Group 113
Group 213
Group 311
Group 413
Change in Fibrosis-4 (FIB-4) Score Secondary · 12 weeks

Mean change in Fibrosis-4 (FIB-4) score from Baseline to Week 1, Week 2, Week 4, Week 8, and Week 12. FIB-4 score is calculated as (age in years \* Aspartate aminotransferase (AST) in U/L)/(platelet count in 10\^9 U/L \* square root of alanine aminotransferase (ALT) in U/L). FIB-4 scores under 1.45 have a negative predictive value of 90% for advanced fibrosis (better outcome) and FIB-4 scores \>3.25 have a positive predictive value of 65% for advanced fibrosis (worse outcome). See Sterling RK, Lissen E, Clumeck N, et. al. Development of a simple noninvasive index to predict significant fibrosi

Week 1
GroupValue95% CI
Group 1-1.7± 0.88
Group 2-2.8± 0.97
Group 3-2.9± 2.68
Group 4-2.0± 0.86
Week 2
GroupValue95% CI
Group 1-1.4± 1.08
Group 2-2.8± 1.06
Group 3-2.9± 2.61
Group 4-1.8± 0.88
Week 4
GroupValue95% CI
Group 1-1.7± 0.88
Group 2-2.9± 1.03
Group 3-2.9± 2.81
Group 4-1.8± 1.07
Week 8
GroupValue95% CI
Group 1-1.7± 1.00
Group 2-2.9± 1.05
Group 3-2.8± 2.67
Group 4-2.1± 0.91
Week 12
GroupValue95% CI
Group 10.0± 0.57
Group 2-1.2± 1.06
Group 3-1.0± 1.51
Group 4-0.8± 0.76
Change in FibroScan Score Secondary · Baseline to end of treatment

Mean change in FibroScan score from Baseline to end of treatment. Fibroscan is a kind of liver elastography measuring liver stiffness in kilopascals (kPa). Higher results are consistent with liver disease (worse outcome).

GroupValue95% CI
Group 10.0± 1.41
Group 22.0± 1.73
Group 30.0± 0.82
Group 41.3± 1.53

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 60 weeks. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Group 1
Serious: 1/13 (8%)
Deaths: 0/13
Group 2
Serious: 0/13 (0%)
Deaths: 0/13
Group 3
Serious: 0/11 (0%)
Deaths: 0/11
Group 4
Serious: 1/14 (7%)
Deaths: 1/14

Serious adverse events (2 terms)

ReactionSystemGroup 1Group 2Group 3Group 4
Hepatocellular carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Mixed hepatocellular cholangiocarcinomaHepatobiliary disorders
Other adverse events (59 terms — click to expand)

ReactionSystemGroup 1Group 2Group 3Group 4
ChromaturiaRenal and urinary disorders
DiarrhoeaGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Abdominal discomfortGastrointestinal disorders
Abdominal distensionGastrointestinal disorders
Faeces softGastrointestinal disorders
NasopharyngitisInfections and infestations
Blood lactate dehydrogenase increasedInvestigations
DizzinessNervous system disorders
HeadacheNervous system disorders
Atrioventricular block first degreeCardiac disorders
Scleral discolourationEye disorders
Swelling of eyelidEye disorders
Abdominal painGastrointestinal disorders
ConstipationGastrointestinal disorders
Dry mouthGastrointestinal disorders
DyspepsiaGastrointestinal disorders
Epigastric discomfortGastrointestinal disorders
EructationGastrointestinal disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
NauseaGastrointestinal disorders
ToothacheGastrointestinal disorders
Chest discomfortGeneral disorders
FatigueGeneral disorders
HungerGeneral disorders
Influenza like illnessGeneral disorders
PyrexiaGeneral disorders
ThirstGeneral disorders
JaundiceHepatobiliary disorders
InfluenzaInfections and infestations
EpicondylitisInjury, poisoning and procedural complications
Haemoglobin decreasedInvestigations
Heart rate increasedInvestigations
Transaminases increasedInvestigations
Decreased appetiteMetabolism and nutrition disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Back painMusculoskeletal and connective tissue disorders
MyalgiaMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders

Most-reported serious reactions: Hepatocellular carcinoma, Mixed hepatocellular cholangiocarcinoma.

Data from ClinicalTrials.gov NCT03905655 adverse events section.

Sponsor's own description

This randomized controlled trial is designed to evaluate safety, effectiveness and pharmacokinetic-pharmacodynamic (PK/PD) relationships associated with three different Nitazoxanide (NTZ) treatment regimens added to Tenofovir Disoproxil Fumarate (TDF), Tenofovir Alafenamide (TAF) or Entecavir (ETV) in treating Chronic Hepatitis B (CHB).

Publications & conference data

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

  1. Discovery and development of safe-in-man broad-spectrum antiviral agents.
    Andersen PI, Ianevski A, Lysvand H, Vitkauskiene A, et al · · 2020 · cited 174× · PMID 32081774 · DOI 10.1016/j.ijid.2020.02.018
  2. Pathophysiology and Treatment Options for Hepatic Fibrosis: Can It Be Completely Cured?
    Khanam A, Saleeb PG, Kottilil S. · · 2021 · cited 86× · PMID 34064375 · DOI 10.3390/cells10051097
  3. Therapeutic Potential of Nitazoxanide: An Appropriate Choice for Repurposing versus SARS-CoV-2?
    Stachulski AV, Taujanskas J, Pate SL, Rajoli RKR, et al · · 2021 · cited 37× · PMID 33352056 · DOI 10.1021/acsinfecdis.0c00478
  4. Toward a new era of hepatitis B virus therapeutics: The pursuit of a functional cure.
    Tsounis EP, Tourkochristou E, Mouzaki A, Triantos C. · · 2021 · cited 33× · PMID 34135551 · DOI 10.3748/wjg.v27.i21.2727
  5. Strategy, Progress, and Challenges of Drug Repurposing for Efficient Antiviral Discovery.
    Li X, Peng T. · · 2021 · cited 25× · PMID 34017257 · DOI 10.3389/fphar.2021.660710
  6. Therapeutic potential of salicylamide derivatives for combating viral infections.
    Xu J, Xue Y, Bolinger AA, Li J, et al · · 2023 · cited 10× · PMID 36905090 · DOI 10.1002/med.21940
  7. Targeting HBV cccDNA Levels: Key to Achieving Complete Cure of Chronic Hepatitis B.
    He W, Zheng Z, Zhao Q, Zhang R, et al · · 2024 · cited 9× · PMID 39770359 · DOI 10.3390/pathogens13121100

Verify or expand the search:

Other trials of Nitazoxanide

Trials testing the same drug.

Other recruiting trials for Chronic Hepatitis B

Currently open trials in the same condition.

Other Romark Laboratories L.C. trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03905655.

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