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

NCT03905655 | Completed Phase 2 Results FDA Drug

• 1 other identifier: RM08-2001
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief 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 Hepatitis B (CHB).

Conditions

Chronic Hepatitis B

Outcome Measures

Primary Outcomes (1)

• Mean Change in Quantitative Hepatitis B Surface Antigen (qHBsAg)

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

  Baseline to 12 weeks

Secondary Outcomes (7)

• Sustained HBsAg Loss With Suppression of HBV DNA for 24 Weeks After the End of Treatment

  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

  8 weeks

• Hepatitis B Surface Antigen (HBsAg) Loss

  12 weeks

• Hepatitis B Surface Antigen (HBsAg) Seroconversion

  12 weeks

• Hepatitis B Virus DNA Suppression

  12 weeks

Study Arms (4)

Group 1

PLACEBO COMPARATOR

Three placebo tablets administered orally twice daily with food in addition to continuing TDF, TAF or ETV therapy

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

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

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

Drug: Nitazoxanide

Interventions

Placebo Oral Tablet DRUG

Number of placebo tablets administered orally depends on the arm

Group 1; Group 2; Group 3

Nitazoxanide DRUG

Number of Nitazoxanide 300 mg extended release tablets administered orally depends on the arm

Also known as: NTZ, NT-300

Group 2; Group 3; Group 4

Eligibility Criteria

• Age: 21 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Unable to take oral medications
• 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
• 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

Sponsors & Collaborators

• Romark Laboratories L.C.: lead

Study Sites (1)

National University Hospital

Singapore, Singapore

Location

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

nitazoxanide

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

This study was a pilot study with a small number of participants.

Results Point of Contact

• Title: Jessica Fulgencio
• Organization: Romark Laboratories, L.C.

jessica.fulgencio@romark.com

813-282-8544

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Patients are randomized 1:1:1:1 (12 subjects per group)

Study Record Dates

• First Submitted: April 4, 2019
• First Posted: April 5, 2019
• Study Start: October 22, 2019
• Primary Completion: March 10, 2021
• Study Completion: October 11, 2021
• Last Updated: November 7, 2023
• Results First Posted: November 7, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)