Chronic Hepatitis BPhase 2NCT03905655
Study of Nitazoxanide Compared to Placebo in Subjects With HBeAG-Negative Chronic Hepatitis B
A Phase 2 study testing Nitazoxanide in people with Chronic Hepatitis B, run by Romark Laboratories L.C. at 1 site in Singapore.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 21 to 100 years
- Conditions the study is for
- Chronic Hepatitis B
- What is being tested?
- Nitazoxanide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 51 participants
- Where
- 1 siteSingapore
- Study dates
- 22 Oct 2019to 11 Oct 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age at least 21 years
- CHB virus infection (serum HBsAg-positive for at least 6 months or serum HBsAg-positive and negative immunoglobulin M (IgM) antibodies to Hepatitis B Virus (HBV) core antigen (IgM anti-HBc))
- Hepatitis B e Antigen (HBeAg) negative
- Virologically suppressed (HBV DNA less than the lower limit of quantitation) for at least 12 months on Tenofovir Disoproxil Fumarate (TDF), Tenofovir Alafenamide (TAF) or Entecavir (ETV) therapy
- Quantitative HBsAg greater than 100 IU/mL
- Alanine Aminotransferase (ALT) below 1.5 times the upper limit of normal
- Able to comply with the study requirements
Who cannot join
- Unable to take oral medications
- Females who are pregnant, breast-feeding or not using birth control. A double barrier method, oral birth control pills administered for at least 2 monthly cycles prior to study drug administration, an intrauterine device (IUD), or medroxyprogesterone acetate administered intramuscularly for a minimum of one month prior to study drug administration are acceptable methods of birth control for inclusion into the study. In addition, female subjects should have a baseline pregnancy test and should agree to continue an acceptable method of birth control for the duration of the study (including follow-up) if sexually active.
- Any investigational drug therapy within 30 days prior to enrollment
- Other causes of liver disease
- Co-infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis D virus (HDV) based on an enzyme immunoassay (EIA)
- History of alcoholism or with an alcohol consumption of greater than 40 g per day
Show all 17Show fewer
- Clinically unstable
- Any concomitant condition that, in the opinion of the investigator would preclude evaluation of response or make it unlikely that the contemplated course of therapy and follow-up could be completed
- History of hypersensitivity or intolerance to NTZ or any of the excipients comprising the NTZ tablets
- Hepatocellular carcinoma
- Decompensated liver disease including history of ascites, bleeding esophageal varices, portal hypertension or hepatic encephalopathy
- FibroScan® score greater than 11 or history of cirrhosis on liver biopsy
- Creatinine clearance <65 ml/minute (by the Cockcroft-Gault equation using ideal body weight)
- History of clinically relevant psychiatric disease, seizures, central nervous system dysfunction, severe pre-existing cardiac, renal, pathologic bone fracture or other risk factors for osteoporosis, hematological disease or medical illness that in the investigator's opinion might interfere with therapy
- Malignant disease within 3 years of trial entry
- Rheumatological conditions, inflammatory bowel disease or psoriasis requiring or anticipated to require biological/immunosuppressive therapies
- Subjects taking or anticipated to need medications considered to be major CYP2C8 substrates
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized Double-Blind Study of Nitazoxanide Compared to Placebo in Subjects With HBeAG-Negative Chronic Hepatitis B Virologically Suppressed for at Least Twelve Months on Tenofovir Disoproxil Fumarate, Tenofovir Alafenamide or Entecavir
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).
- Conditions
- Chronic Hepatitis B
- Being tested
- Placebo Oral Tablet, Nitazoxanide
- Medical subject headings
- Hepatitis B, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Placebo Oral TabletDrug
Number of placebo tablets administered orally depends on the arm
NitazoxanideDrug
Also called NTZ, NT-300
Number of Nitazoxanide 300 mg extended release tablets administered orally depends on the arm
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Placebo comparator | Three placebo tablets administered orally twice daily with food in addition to continuing TDF, TAF or ETV therapy Receives: Drug: Placebo Oral Tablet |
| Group 2 | Active comparator | Two 300 mg NTZ tablets and one placebo tablet administered orally in the morning and three placebo tablets in the evening in addition to continuing TDF, TAF or ETV therapy Receives: Drug: Placebo Oral Tablet; Drug: Nitazoxanide |
| Group 3 | Active comparator | Two 300 mg NTZ tablets and one placebo tablet administered orally twice daily with food in addition to continuing TDF, TAF or ETV therapy Receives: Drug: Placebo Oral Tablet; Drug: Nitazoxanide |
| Group 4 | Active comparator | Three 300 mg NTZ tablets administered orally twice daily with food in addition to continuing TDF, TAF or ETV therapy Receives: Drug: Nitazoxanide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Change in Quantitative Hepatitis B Surface Antigen (qHBsAg)
Mean change in quantitative Hepatitis B Surface Antigen (qHBsAg) from Baseline
Measured: Baseline to 12 weeks
Secondary outcomes (7)
Sustained HBsAg Loss With Suppression of HBV DNA for 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
Measured: Baseline to 24 weeks after the end of treatment
Change in Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline to Different Time Points on Treatment
Change in mean Quantitative Hepatitis B Surface Antigen (qHBsAg) from Baseline to Day 3, Week 1, Week 2, Week 4, and Week 8
Measured: 8 weeks
Hepatitis B Surface Antigen (HBsAg) Loss
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
Measured: 12 weeks
Hepatitis B Surface Antigen (HBsAg) Seroconversion
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
Measured: 12 weeks
Hepatitis B Virus DNA Suppression
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
Measured: 12 weeks
Change in Fibrosis-4 (FIB-4) Score
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 fibrosis patients with HIV/HCV co-infection. Hepatology 2006;43:1317-1325.
Measured: 12 weeks
Change in FibroScan Score
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).
Measured: Baseline to end of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2019
- Study start22 Oct 2019
- Primary completion10 Mar 2021
- Study completion11 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic Hepatitis BStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients are randomized 1:1:1:1 (12 subjects per group)
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- Romark Laboratories L.C.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03905655
- Sponsor's protocol ID
- RM08-2001
- Status last verified
- Nov 2023
- First submitted
- 4 Apr 2019
- Last updated
- 7 Nov 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Double-Blind Study of Nitazoxanide Compared to Placebo in Subjects With HBeAG-Negative Chronic Hepatitis B Virologically Suppressed for at Least Twelve Months on Tenofovir Disoproxil Fumarate, Tenofovir Alafenamide or Entecavir
- ClinicalTrials.gov ID
- NCT03905655
- Acronym / sponsor ID
- RM08-2001
- Conditions
- Chronic Hepatitis B
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- Romark Laboratories L.C.Industry (pharma, biotech, devices)
- Study start
- 22 Oct 2019 (actual)
- Primary completion
- 10 Mar 2021 (actual)
- Study completion
- 11 Oct 2021 (actual)
- First posted
- 5 Apr 2019 (actual)
- Results
- Posted 7 Nov 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- Patients are randomized 1:1:1:1 (12 subjects per group)
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Placebo comparator | Drug: Placebo Oral TabletThree placebo tablets administered orally twice daily with food in addition to continuing TDF, TAF or ETV therapy |
| Group 2 | Active comparator | Drug: Placebo Oral Tablet, Drug: NitazoxanideTwo 300 mg NTZ tablets and one placebo tablet administered orally in the morning and three placebo tablets in the evening in addition to continuing TDF, TAF or ETV therapy |
| Group 3 | Active comparator | Drug: Placebo Oral Tablet, Drug: NitazoxanideTwo 300 mg NTZ tablets and one placebo tablet administered orally twice daily with food in addition to continuing TDF, TAF or ETV therapy |
| Group 4 | Active comparator | Drug: NitazoxanideThree 300 mg NTZ tablets administered orally twice daily with food in addition to continuing TDF, TAF or ETV therapy |
Who may qualify
- Ages
- 21 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age at least 21 years
- CHB virus infection (serum HBsAg-positive for at least 6 months or serum HBsAg-positive and negative immunoglobulin M (IgM) antibodies to Hepatitis B Virus (HBV) core antigen (IgM anti-HBc))
- Hepatitis B e Antigen (HBeAg) negative
- Virologically suppressed (HBV DNA less than the lower limit of quantitation) for at least 12 months on Tenofovir Disoproxil Fumarate (TDF), Tenofovir Alafenamide (TAF) or Entecavir (ETV) therapy
- Quantitative HBsAg greater than 100 IU/mL
Key exclusion criteria (17 listed)
- Unable to take oral medications
- Females who are pregnant, breast-feeding or not using birth control. A double barrier method, oral birth control pills administered for at least 2 monthly cycles prior to study drug administration, an intrauterine device (IUD), or medroxyprogesterone acetate administered intramuscularly for a minimum of one month prior to study drug administration are acceptable methods of birth control for inclusion into the study. In addition, female subjects should have a baseline pregnancy test and should agree to continue an acceptable method of birth control for the duration of the study (including follow-up) if sexually active.
- Any investigational drug therapy within 30 days prior to enrollment
- Other causes of liver disease
- Co-infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis D virus (HDV) based on an enzyme immunoassay (EIA)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebo Oral TabletNumber of placebo tablets administered orally depends on the arm | Drug | Group 1, Group 2, Group 3 |
| NitazoxanideAlso: NTZ, NT-300Number of Nitazoxanide 300 mg extended release tablets administered orally depends on the arm | Drug | Group 2, Group 3, Group 4 |
Primary outcome
Mean Change in Quantitative Hepatitis B Surface Antigen (qHBsAg)
Time frame: Baseline to 12 weeks
Mean change in quantitative Hepatitis B Surface Antigen (qHBsAg) from Baseline
7 secondary outcomes
Sustained HBsAg Loss With Suppression of HBV DNA for 24 Weeks After the End of Treatment
Time frame: Baseline to 24 weeks after the end of treatment
Change in Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline to Different Time Points on Treatment
Time frame: 8 weeks
Hepatitis B Surface Antigen (HBsAg) Loss
Time frame: 12 weeks
Hepatitis B Surface Antigen (HBsAg) Seroconversion
Time frame: 12 weeks
Hepatitis B Virus DNA Suppression
Time frame: 12 weeks
Change in Fibrosis-4 (FIB-4) Score
Time frame: 12 weeks
Change in FibroScan Score
Time frame: Baseline to end of treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Nov 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nitazoxanide in people with Chronic Hepatitis B, run by Romark Laboratories L.C. at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Nov 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Change in Quantitative Hepatitis B Surface Antigen (qHBsAg) (time frame: Baseline to 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Nov 2023.