Chronic Hepatitis BPhase 4NCT01379508
Telbivudine or Tenofovir Treatment in HBeAg-negative Chronic Hepatitis B Patients Based on the Roadmap Concept
A Phase 4 study testing telbivudine and tenofovir disoproxil fumarate in people with Chronic Hepatitis B, run by Novartis Pharmaceuticals at 34 sites in 8 countries.
Trial summary
The purpose of this study is to evaluate the efficacy and safety following the Roadmap Concept strategy with an initial monotherapy using either telbivudine or tenofovir in HBeAg negative CHB patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Hepatitis B
- What is being tested?
- telbivudine and tenofovir disoproxil fumarate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 241 participants
- Where
- 34 sitesin 8 countries
- Study dates
- 21 Mar 2011to 10 Dec 2015
- Phase
- Phase 4
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female, at least 18 years of age
- Documented compensated HBeAg negative CHB defined by all of the following:
- Detectable serum HBsAg at screening visit and at least 6 months prior;
- HBeAg negative at the screening visit with positive HBeAb;
- Serum HBV DNA > 2000 IU/mL Serum ALT level > 1×ULN and <10×ULN at screening visit; patient with normal ALT ≤1xULN at screening are eligible, with moderate liver inflammation or fibrosis, complensated liver sirrhosis, ALT level >1xULN wtihin last 6 months
Who cannot join
- Co-infected with HCV, HDV or HIV.
- Received treatment of nucleoside or nucleotide drugs at any time
- Received IFN or other immunomodulatory treatment within six months before Screening
- Pregnant or nursing (lactating) women
- Clinical signs/symptoms of hepatic decompensation
- History of myopathy, myositis or persistent muscle weakness
- history of clinical and laboratory evidence of chronic renal insufficency
Trial locations and contacts
34 sites in 8 countries.
34 sites in 8 countries
Germany7 sites
Novartis Investigative Site
Frankfurt, 60590
Novartis Investigative Site
Freiburg im Breisgau, 79106
Novartis Investigative Site
Hamburg, 20099
Novartis Investigative Site
Hanover, 30625
Novartis Investigative Site
Herne, 44623
Novartis Investigative Site
Leipzig, 04103
Novartis Investigative Site
Würzburg, 97080
Russia7 sites
Novartis Investigative Site
Moscow, 111123
Novartis Investigative Site
Moscow, 119333
Novartis Investigative Site
Moscow, 119992
Novartis Investigative Site
Moscow, 127473
Novartis Investigative Site
Moscow, 129110
Novartis Investigative Site
Moscow
Novartis Investigative Site
Saint Petersburg, 194044
Bulgaria5 sites
Novartis Investigative Site
Sofia, 1407
Novartis Investigative Site
Sofia, 1413
Novartis Investigative Site
Sofia, 1431
Novartis Investigative Site
Sofia, 1527
Novartis Investigative Site
Varna, 9010
Greece4 sites
Novartis Investigative Site
Alexandroupoli, Evros, 681 00
Novartis Investigative Site
Athens, GR, 115 21
Novartis Investigative Site
Athens, 115 27
Novartis Investigative Site
Thessaloniki, GR, 546 42
Spain4 sites
Novartis Investigative Site
Barcelona, Catalonia, 08003
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
Majadahonda, Madrid, 28222
Novartis Investigative Site
Tarragona, Catalonia, 43005
Turkey (Türkiye)4 sites
Novartis Investigative Site
Diyarbakır, 21280
Novartis Investigative Site
Istanbul, TUR, 34098
Novartis Investigative Site
Izmir, 35040
Novartis Investigative Site
Trabzon, 61080
Austria2 sites
Novartis Investigative Site
Innsbruck, A-6020
Novartis Investigative Site
Vienna, 1090
About this study
Official title: OPTIMA: A Randomized, Open-label, 156-week Treatment Study to Evaluate the Efficacy and Safety of Telbivudine or Tenofovir Treatment in HBeAg-negative Chronic Hepatitis B Patients Based on the Roadmap Concept
The purpose of this study is to evaluate the efficacy and safety following the Roadmap Concept strategy with an initial monotherapy using either telbivudine or tenofovir in HBeAg negative CHB patients. The data from the study should allow for the validation of the Roadmap concept in a prospective manner, for both telbivudine and tenofovir treated HBeAg negative CHB patients. As part of a post-approval commitment to the European Health Authorities, the data will also be used to provide an optimized clinical treatment strategy for better clinical use of telbivudine in European HBeAg negative patients. Furthermore, the data from the study will contribute to a better scientific understanding, disease management and treatment of HBeAg negative CHB patients.
- Conditions
- Chronic Hepatitis B
- Being tested
- telbivudine, tenofovir disoproxil fumarate
- 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.
telbivudineDrug
Also called LDT600
600 mg film-coated tablets taken as 600 mg once daily
tenofovir disoproxil fumarateDrug
300 mg tablets taken as 300 mg once daily
| Study group | Role | What they receive |
|---|---|---|
| telbivudine | Experimental | telbivudine 600 mg tablet orally (p.o.) once daily for up to 156 weeks. Patients with HBV DNA ≥ 300 copies/mL at Week 24 were to initiate add-on therapy with tenofovir 300 mg tablets p.o. once daily for the remaining weeks of treatment. The investigator was to initiate tenofovir add-on therapy within 2 weeks of central laboratory confirmation. Patients with HBV DNA < 300 copies/mL at Week 24 were to continue to receive telbivudine monotherapy Receives: Drug: telbivudine |
| tenofovir | Active comparator | tenofovir 300 mg tablets p.o. once daily for up to 156 weeks. Patients with HBV DNA ≥ 300 copies/mL at Week 24 were to initiate add-on therapy with telbivudine 600 mg tablet p.o. once daily for the remaining weeks of treatment. The investigator was to initiate telbivudine add-on therapy within 2 weeks of central laboratory confirmation. Patients with HBV DNA < 300 copies/mL at Week 24 were to continue to receive tenofovir monotherapy Receives: Drug: tenofovir disoproxil fumarate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Achieving HBV DNA < 300 Copies/mL (51 IU/mL) at Week 52 (rITT Population) -
The primary objective of the study is to compare the efficacy of Roadmap-Concept-based telbivudine treatment versus Roadmap-Concept-based tenofovir treatment in HBeAg-negative CHB patients. The rate of HBV DNA < 300 copies/mL (51 IU/mL) at week 52 will be used for the comparison of the efficacy. The hypothesis is that the aggregated rate of HBV DNA < 300 copies/mL (51 IU/mL) at week 52 of Telbivudine (ARM 1) is non-inferior to Tenofovir (ARM 2). For the "treating missing as failure" analysis, patients who came for their primary endpoint Week 52 visit within the ± 7-day window but not on the exact designated day of the visit were treated as "missing data."
Measured: week 52
Secondary outcomes (3)
Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT)
To assess the antiviral efficacy, as evaluated by the percentage of patients achieving HBV DNA <300 copies/mL (51 IU/mL), ALT normalization, HBsAg loss, HBsAg conversion, virologic breakthrough (VB) at study visit, cumulative VB by study defined study period, cumulative treatment-emergent resistance
Measured: week 24, 52, 104
Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT)
To assess the antiviral efficacy, as evaluated by the percentage of patients achieving HBV DNA <300 copies/mL (51 IU/mL) at Week156, ALT normalization, HBsAg loss, development of HBsAg conversion , cumulative tx emergent resistance, HBV DNA <300 copies/mL with HBV DNA <7 log at Baseline
Measured: 156 weeks
eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study
eGFR changes were calculated using the Modification of Diet in Renal Disease (MDRD) formula: GFR = 186 x (sCr)^(-1.154) x (age)^-0.203 with Female: Multiply GFR by 0.742; Black: Multiply GFR by 1.210. sCr is Serum Creatinine in mg/dl (measured at each scheduled visit). Age in years at visit (=[sCr sample collection date -Date of birth]/365.25). Weight in kilograms, as measured at the visit or the closest previous visit Safety population.
Measured: Baseline, 24 weeks, 52 weeks, 104 weeks, 156 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2011 (estimated)
- Study start21 Mar 2011
- Primary completion10 Dec 2015
- Study completion10 Dec 2015
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.
- More trials run by Novartis PharmaceuticalsThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 241 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01379508
- Sponsor's protocol ID
- CLDT600A2409
- Other IDs
- 2007-000180-13
- Status last verified
- Mar 2018
- First submitted
- 21 Jun 2011
- Last updated
- 5 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- OPTIMA: A Randomized, Open-label, 156-week Treatment Study to Evaluate the Efficacy and Safety of Telbivudine or Tenofovir Treatment in HBeAg-negative Chronic Hepatitis B Patients Based on the Roadmap Concept
- ClinicalTrials.gov ID
- NCT01379508
- Acronym / sponsor ID
- CLDT600A2409
- Conditions
- Chronic Hepatitis B
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 241 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 21 Mar 2011 (actual)
- Primary completion
- 10 Dec 2015 (actual)
- Study completion
- 10 Dec 2015 (actual)
- First posted
- 23 Jun 2011 (estimated)
- Results
- Posted 5 Nov 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the efficacy and safety following the Roadmap Concept strategy with an initial monotherapy using either telbivudine or tenofovir in HBeAg negative CHB patients. The data from the study should allow for the validation of the Roadmap concept in a prospective manner, for both telbivudine and tenofovir treated HBeAg negative CHB patients. As part of a post-approval commitment to the European Health Authorities, the data will also be used to provide an optimized clinical treatment strategy for better clinical use of telbivudine in European HBeAg negative patients. Furthermore, the data from the study will contribute to a better scientific understanding, disease management and treatment of HBeAg negative CHB patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| telbivudine | Experimental | Drug: telbivudinetelbivudine 600 mg tablet orally (p.o.) once daily for up to 156 weeks. Patients with HBV DNA ≥ 300 copies/mL at Week 24 were to initiate add-on therapy with tenofovir 300 mg tablets p.o. once daily for the remaining weeks of treatment. The investigator was to initiate tenofovir add-on therapy within 2 weeks of central laboratory confirmation. Patients with HBV DNA < 300 copies/mL at Week 24 were to continue to receive telbivudine monotherapy |
| tenofovir | Active comparator | Drug: tenofovir disoproxil fumaratetenofovir 300 mg tablets p.o. once daily for up to 156 weeks. Patients with HBV DNA ≥ 300 copies/mL at Week 24 were to initiate add-on therapy with telbivudine 600 mg tablet p.o. once daily for the remaining weeks of treatment. The investigator was to initiate telbivudine add-on therapy within 2 weeks of central laboratory confirmation. Patients with HBV DNA < 300 copies/mL at Week 24 were to continue to receive tenofovir monotherapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male or female, at least 18 years of age
- Detectable serum HBsAg at screening visit and at least 6 months prior;
- HBeAg negative at the screening visit with positive HBeAb;
- Serum HBV DNA > 2000 IU/mL Serum ALT level > 1×ULN and <10×ULN at screening visit; patient with normal ALT ≤1xULN at screening are eligible, with moderate liver inflammation or fibrosis, complensated liver sirrhosis, ALT level >1xULN wtihin last 6 months
Key exclusion criteria (7 listed)
- Co-infected with HCV, HDV or HIV.
- Received treatment of nucleoside or nucleotide drugs at any time
- Received IFN or other immunomodulatory treatment within six months before Screening
- Pregnant or nursing (lactating) women
- Clinical signs/symptoms of hepatic decompensation
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 |
|---|---|---|
| telbivudineAlso: LDT600600 mg film-coated tablets taken as 600 mg once daily | Drug | telbivudine |
| tenofovir disoproxil fumarate300 mg tablets taken as 300 mg once daily | Drug | tenofovir |
Primary outcome
Percentage of Participants Achieving HBV DNA < 300 Copies/mL (51 IU/mL) at Week 52 (rITT Population) -
Time frame: week 52
The primary objective of the study is to compare the efficacy of Roadmap-Concept-based telbivudine treatment versus Roadmap-Concept-based tenofovir treatment in HBeAg-negative CHB patients. The rate of HBV DNA < 300 copies/mL (51 IU/mL) at week 52 will be used for the comparison of the efficacy. The hypothesis is that the aggregated rate of HBV DNA < 300 copies/mL (51 IU/mL) at week 52 of Telbivudine (ARM 1) is non-inferior to Tenofovir (ARM 2). For the "treating missing as failure" analysis, patients who came for their primary endpoint Week 52 visit within the ± 7-day window but not on the exact designated day of the visit were treated as "missing data."
3 secondary outcomes
Percentage of Patients Achieving Secondary Efficacy Endpoints (rITT)
Time frame: week 24, 52, 104
Percentage of Participants Achieving Secondary Efficacy Endpoints at Week 156 (mITT)
Time frame: 156 weeks
eGFR Change From Baseline in Telbivudine Arm vs Tenofovir Arm Over the Course of the Study
Time frame: Baseline, 24 weeks, 52 weeks, 104 weeks, 156 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
34 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing telbivudine and tenofovir disoproxil fumarate in people with Chronic Hepatitis B, run by Novartis Pharmaceuticals at 34 sites in 8 countries.
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 5 inclusion and 7 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 5 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 34 sites in Germany, Russia, Bulgaria, Greece, Spain and 3 more countries. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 5 Nov 2018). 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?
Percentage of Participants Achieving HBV DNA < 300 Copies/mL (51 IU/mL) at Week 52 (rITT Population) - (time frame: week 52). 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 5 Nov 2018.