Hepatitis B, ChronicPhase 3NCT03759782
Ribavirin to Enhance Hepatitis B Virus Nucleotide Analog Antiviral Activity
A Phase 3 study testing Ribavirin and Tenofovir in people with Hepatitis B, Chronic, run by Ottawa Hospital Research Institute at 2 sites in Canada.
Trial summary
Hepatitis B virus (HBV) leads to life-threatening disease like liver failure and liver cancer. For most, a cure is unattainable as current HBV antiviral therapy (using nucleoside analogues) are not able to clear the virus from their liver. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatitis B, Chronic
- What is being tested?
- Ribavirin and Tenofovir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 2 sitesCanada
- Study dates
- 10 Jan 2019to 30 Sep 2022
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HBV Hepatitis B surface antigen (HBsAg) positive for a minimum of 24 weeks
- HBV DNA level >20,000 IU/mL
- ≥ 18 years of age
Who cannot join
- Willingness and ability to sign an informed consent
- HBV nucleos(t)ides and/or interferon exposure within 24 weeks of study medication dosing
- HIV and other immune compromising condition (e.g. cancer with the exception of non-invasive cutaneous malignancy, autoimmune condition) or therapy (i.e. systemic steroids, chemotherapy)
- HCV co-infected
- Cirrhosis (defined by biopsy criteria or as >18.4 kilopascal (kPa) by transient elastography)
- Creatinine Clearance <60 ml/min
Show all 9Show fewer
- Baseline hemoglobin <130 g/L in males and <120 g/L in females
- Unwilling or unable to use contraception (unless confirmed surgical sterilization)
- Pregnancy confirmed by blood test
Trial locations and contacts
2 sites in 1 country.
Canada2 sites, 2 recruiting
- Recruiting
Cumming School of Medicine, University of Calgary
Calgary, Alberta, T2N4Z6
Carla Coffin, MD, 403-592-5049, cacoffin@ucalgary.ca
Leah Kilvert, BSCN, 403.220.8966, lvkilver@ucalgary.ca
- Recruiting
Ottawa Hospital Research Institute
Ottawa, Ontario, K1H8L6
Curtis Cooper, MD, 6137378924, ccooper@toh.ca
Miriam Muir, RN, 6137378899 ext. 72723, mmuir@toh.ca
About this study
Official title: Use of Immune Modulatory Properties of Ribavirin to Enhance Hepatitis B Virus Nucleotide Analog Antiviral Activity: Proposal for Pilot Clinical Trial
Hepatitis B virus (HBV) leads to life-threatening disease like liver failure and liver cancer. For most, a cure is unattainable as current HBV antiviral therapy (using nucleoside analogues) are not able to clear the virus from their liver. While HBV treatments are typically administered alone (monotherapy), this study will explore the use of Ribavirin in combination with standard therapy to enhance current treatment regimens. Ribavirin is commonly used to treat Hepatitis C Virus (HCV) but there is evidence that Ribavirin also induces immune effects that are beneficial in HBV treatment. The aim of this study is to determine whether combination of Ribavirin and a nucleoside analog is more effective compared to nucleoside analog treatment alone. Enrolled patients will be followed for treatment response according to standard clinical and virological tests, as well as immune response to HBV. Our ultimate goal is to find a more effective treatment and improve health outcomes for persons living with HBV.
- Conditions
- Hepatitis B, Chronic
- Being tested
- Ribavirin, Tenofovir
- 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.
RibavirinDrug
Ribavirin will be added to the standard of care treatment (tenofovir) regime for 24 weeks.
TenofovirDrug
Tenofovir as per standard of care
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | Tenofovir (TDF) 300 mg po once a day (OD) Receives: Drug: Tenofovir |
| Group 2 | Active comparator | Tenofovir 300 mg po OD + Ribavirin 400 mg twice a day (BID) if <70kg / 600 mg every (q) in the morning (AM) and 400 mg q in the evening (PM) if ≥70kg Receives: Drug: Ribavirin; Drug: Tenofovir |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Decline of Participants Serum HBV DNA values for both study arms at each study.
The absolute decline in HBV DNA and quantitative HBsAg titre will be compared with baseline level at each study visit overall and between study arms (with or without RBV).
Measured: 24 weeks
Secondary outcomes (3)
Fibroscan score
Individual fibroscan scores pre and post treatment for each group, using fibrosis scores calculated in kilopascal F0 representing no fibrosis and F4 value indicating cirrhosis.
Measured: 24 weeks
Liver enzyme values
Participants individual reduction in liver enzymes at each visit.
Measured: 24 weeks
Number of participants with treatment related adverse events as assessed by CTCAE v4.0.
Safety profile of TDF plus Ribavirin regime
Measured: 28 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2018
- Study start10 Jan 2019
- Primary completion31 Jan 2022 (estimated)
- Study completion30 Sep 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatitis B, ChronicStudies of the same condition, open and under way.
- More trials run by Ottawa Hospital Research InstituteThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Open-label
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ottawa Hospital Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Curtis L Cooper, MD, Principal investigator, Ottawa Hospital Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03759782
- Sponsor's protocol ID
- 20180733
- Status last verified
- Sep 2021
- First submitted
- 2 Oct 2018
- Last updated
- 14 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Keeshan A, Coffin C, Vachon A, Patel N, Fung S, Mortimer L, Crawley A, Ma M, Osiowy C, Cooper C. Ribavirin Does Not Enhance Hepatitis B Virus Nucleotide Antiviral Activity: A Pilot Study. Clin Invest Med. 2022 Dec 31;45(4):E11-15. doi: 10.25011/cim.v45i4.39274.
PubMed 36586101
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of Immune Modulatory Properties of Ribavirin to Enhance Hepatitis B Virus Nucleotide Analog Antiviral Activity: Proposal for Pilot Clinical Trial
- ClinicalTrials.gov ID
- NCT03759782
- Acronym / sponsor ID
- 20180733
- Conditions
- Hepatitis B, Chronic
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Ottawa Hospital Research InstituteUniversity, hospital or other
- Study start
- 10 Jan 2019 (actual)
- Primary completion
- 31 Jan 2022 (estimated)
- Study completion
- 30 Sep 2022 (estimated)
- First posted
- 30 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hepatitis B virus (HBV) leads to life-threatening disease like liver failure and liver cancer. For most, a cure is unattainable as current HBV antiviral therapy (using nucleoside analogues) are not able to clear the virus from their liver. While HBV treatments are typically administered alone (monotherapy), this study will explore the use of Ribavirin in combination with standard therapy to enhance current treatment regimens. Ribavirin is commonly used to treat Hepatitis C Virus (HCV) but there is evidence that Ribavirin also induces immune effects that are beneficial in HBV treatment. The aim of this study is to determine whether combination of Ribavirin and a nucleoside analog is more effective compared to nucleoside analog treatment alone. Enrolled patients will be followed for treatment response according to standard clinical and virological tests, as well as immune response to HBV. Our ultimate goal is to find a more effective treatment and improve health outcomes for persons living with HBV.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Open-label
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Drug: TenofovirTenofovir (TDF) 300 mg po once a day (OD) |
| Group 2 | Active comparator | Drug: Ribavirin, Drug: TenofovirTenofovir 300 mg po OD + Ribavirin 400 mg twice a day (BID) if <70kg / 600 mg every (q) in the morning (AM) and 400 mg q in the evening (PM) if ≥70kg |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- HBV Hepatitis B surface antigen (HBsAg) positive for a minimum of 24 weeks
- HBV DNA level >20,000 IU/mL
- ≥ 18 years of age
Key exclusion criteria (9 listed)
- Willingness and ability to sign an informed consent
- HBV nucleos(t)ides and/or interferon exposure within 24 weeks of study medication dosing
- HIV and other immune compromising condition (e.g. cancer with the exception of non-invasive cutaneous malignancy, autoimmune condition) or therapy (i.e. systemic steroids, chemotherapy)
- HCV co-infected
- Cirrhosis (defined by biopsy criteria or as >18.4 kilopascal (kPa) by transient elastography)
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 |
|---|---|---|
| RibavirinRibavirin will be added to the standard of care treatment (tenofovir) regime for 24 weeks. | Drug | Group 2 |
| TenofovirTenofovir as per standard of care | Drug | Group 1, Group 2 |
Primary outcome
The Decline of Participants Serum HBV DNA values for both study arms at each study.
Time frame: 24 weeks
The absolute decline in HBV DNA and quantitative HBsAg titre will be compared with baseline level at each study visit overall and between study arms (with or without RBV).
3 secondary outcomes
Fibroscan score
Time frame: 24 weeks
Liver enzyme values
Time frame: 24 weeks
Number of participants with treatment related adverse events as assessed by CTCAE v4.0.
Time frame: 28 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2021.
- Derived from this study: PubMed 36586101Keeshan A, Coffin C, Vachon A, Patel N, Fung S, Mortimer L, Crawley A, Ma M, Osiowy C, Cooper C. Ribavirin Does Not Enhance Hepatitis B Virus Nucleotide Antiviral Activity: A Pilot Study. Clin Invest Med. 2022 Dec 31;45(4):E11-15. doi: 10.25011/cim.v45i4.39274.
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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.
Curtis L Cooper, MD principal investigator
Ottawa Hospital Research Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ribavirin and Tenofovir in people with Hepatitis B, Chronic, run by Ottawa Hospital Research Institute at 2 sites in Canada.
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 3 inclusion and 9 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: status not confirmed, as of the sponsor's last update on 14 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. 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. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Curtis L Cooper, MD (613.737.8924, ccooper@toh.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Decline of Participants Serum HBV DNA values for both study arms at each study. (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03759782, which also lists 1 linked publication.
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 14 Sep 2021.