Hepatitis CPhase 1/2NCT01833845
Efficacy, Safety and Tolerability of Ribavirin Monotherapy Followed by Combined Treatment With Ribavirin and Hydroxychloroquine in Patients Infected With Hepatitis C
A Phase 1/2 study testing Ribavirin and Hydroxychloroquine in people with Hepatitis C, run by BioLineRx, Ltd. at 2 sites in France.
Trial summary
Proof-of Concept, Open-Label, Two-Stage Study without Direct Individual Benefit The proposed study design consists of two treatment periods and one treatment arm. Treatment Period 1 involves the administration of RBV monotherapy for a period of 8 weeks and Treatment Period 2 involves administration of up to 16 weeks… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatitis C
- What is being tested?
- Ribavirin and Hydroxychloroquine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 2 sitesFrance
- Study dates
- Apr 2013to Apr 2014
- Phase
- Phase 1/2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female, age ≥ 18.
- Subjects diagnosed to have positive HCV antibodies.
- Subject is diagnosed to have detectable HCV RNA by PCR.
- FibroTest or FibroScan or liver biopsy showing a METAVIR score ≤ F2 and/or
- ≤ A2 within 2 years of the screening visit.
- Subject is a non-responder (null or partial ) OR relapsed following prior Peg-IFN and RBV based treatment lasting for at least 12 consecutive weeks.
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- Platelet count greater than or equal to 100,000 cells/mm3.
- Absolute neutrophil count (ANC) greater than or equal to 1500 cells/mm3.
- Subjects able to comprehend and give written informed consent for participation in this study.
- Women of childbearing potential and all men must agree to use an approved form of contraception (e.g., oral, transdermal patch, implanted contraceptives, intrauterine device, diaphragm, condom, abstinence or surgical sterility) prior to study entry and for the duration of study participation through 7 months after the last dose of study medication. Confirmation that the female patient is not pregnant must be established by a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
- Subject is willing to be treated and commit to all visits
Who cannot join
- Contraindication or hypersensitivity to one of the study drugs (HCQ or RBV).
- Patient has anemia (male <13 g/dL; female <12 g/dL), elevated ALT and/or AST >10 x ULN or elevated creatinine (>1.5 mg/dL).
- Concomitant liver disease other than hepatitis C: alcoholic liver disease, autoimmune hepatitis, Wilson's disease, hemochromatosis, alpha-1 antitrypsin deficiency.
- Decompensated cirrhosis (Child Pugh >A).
- Ongoing hepatocellular carcinoma (suggestive imaging study or alpha-fetoprotein (AFP) >50 ng/mL).
- Hepatitis B or Human Immunodeficiency Virus (HIV1 or HIV2) co-infection.
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- Clinically relevant ECG abnormalities on screening or baseline 12-lead ECG, e.g.,
- QTc interval (QTcB or QTcF > 450 ms in males and > 470 ms in females);
- Notable resting bradycardia (HR < 40 bpm);
- Any other significant abnormality suggestive of structural heart disease.
- Family history of congenital long QT syndrome.
- Clinically significant abnormalities on ophthalmic examination.
- Major uncontrolled psychiatric illness. Minor or situational depressions are allowed.
- History of hemoglobinopathy (e.g., thalassemia) or any other cause of or tendency to hemolysis (e.g., G-6-PD deficiency).
- Active illicit drug or alcohol abuse.
- Serious co-morbid conditions such as: heart failure, significant coronary heart disease, chronic obstructive pulmonary disease, poorly controlled diabetes, autoimmune disorders and any malignant diseases (except in situ carcinomas or basal cell carcinoma) in the previous 5 years.
- Patients with chronic renal insufficiency, creatinine clearance < 50 mL/minute and/or undergoing haemodialysis.
- Patients with porphyria or psoriasis.
- Ongoing concomitant treatment with azathioprine, digoxin or medications known to prolong QT interval.
- History of organ transplantation.
- Pregnancy, breast-feeding or unwillingness to practice double contraception or abstinence by the subject of childbearing potential or partner.
- Concurrent participation in any other clinical study or within 180 days 20.Patients with inability to communicate well with the Investigators and staff (i.e., language problem, poor mental development or impaired cerebral function) or any other condition that in the opinion of the Investigator will place the patient at risk or prevent protocol compliance.
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Trial locations and contacts
2 sites in 1 country.
About this study
Official title: An Open-Label Study to Evaluate the Efficacy, Safety and Tolerability of Ribavirin Monotherapy Followed by Combined Treatment With Ribavirin and Hydroxychloroquine in Patients Infected With Hepatitis C
Proof-of Concept, Open-Label, Two-Stage Study without Direct Individual Benefit The proposed study design consists of two treatment periods and one treatment arm. Treatment Period 1 involves the administration of RBV monotherapy for a period of 8 weeks and Treatment Period 2 involves administration of up to 16 weeks combination therapy with RBV plus HCQ.
Read the detailed description
Patients who provide their informed consent and conform to all the inclusion and none of the exclusion criteria will be enrolled into the study and will receive RBV monotherapy for 8 weeks. Subjects will receive weight-based doses (1000 mg/day administered BID [twice daily] for subjects ≤ 75 kg and 1200 mg/day administered BID for subjects > 75 kg). Those subjects receiving 1000 mg/day RBV will take 2 tablets of 200 mg/tablet in the morning and 3 tablets in the evening, and those subjects receiving 1200 mg/day RBV will take 3 tablets morning and evening.
During Treatment Period 2, subjects will receive HCQ 575 mg administered as a single tablet once daily (QD), in addition to continuing the same dose of RBV that was administered during Treatment Period 1, as combination therapy for up to 16 weeks.
Subjects will undergo regular blood sampling throughout Treatment Periods 1 and 2 to measure viral response (HCV RNA). Safety will be assessed throughout the study by collection of adverse event (AE) and concomitant medication data, and routine monitoring of laboratory safety tests, vital signs and 12-lead electrocardiograms (ECG).
Subjects will have their viral response tested following 12 weeks of combination therapy; those who show < 1 log decline in viral load during the combination therapy will have the opportunity to withdraw and transfer to standard of care (SoC) treatment following performance of the "End of Study Treatment" visit.
On completion of study treatment, subjects will be allowed to transfer immediately to SoC treatment in order to maximize the benefit of any reduced viral load resulting from combination therapy with RBV plus HCQ. Subjects will attend the clinical site for an "End of Study Treatment" visit within 2 weeks of the final dose of combination treatment with RBV plus HCQ during which they will undergo a final measurement of HCV RNA, safety assessments as described above and a full physical and ophthalmic examination. The "End of Study Treatment" visit may take place on the same day as the final study visit at week 24.
In the event of subjects achieving viral undetectability during combination therapy, the relevant subjects may be administered additional combination therapy to achieve a total of 24 weeks of viral undetectability. If combination dosing with RBV plus HCQ continues for more than 16 weeks, subjects will continue to attend the clinical site and undergo assessment of safety and viral load at the discretion of the Investigator. However, treatment beyond 16 weeks of combination therapy will be considered compassionate use and will not be considered part of the study. In these subjects, the "End of Study Treatment" visit will take place no more than 2 weeks after the Week 24 visit.
- Conditions
- Hepatitis C
- Being tested
- Ribavirin, Hydroxychloroquine
- Keywords
- HCV, Hepatitis C, Hep-C
- Medical subject headings
- Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RibavirinDrug
Also called RBV
weight-based doses (1000 mg/day administered BID [twice daily] for subjects ≤ 75 kg and 1200 mg/day administered BID for subjects > 75 kg). Those subjects receiving 1000 mg/day RBV will take 2 tablets of 200 mg/tablet in the morning and 3 tablets in the evening, and those subjects receiving 1200 mg/day RBV will take 3 tablets morning and evening.
Also called HCQ
subjects will receive HCQ 575 mg administered as a single tablet once daily (QD)
| Study group | Role | What they receive |
|---|---|---|
| Ribavirin+HCQ | Experimental | Administration of RBV monotherapy for a period of 8 weeks following administration of up to 16 weeks combination therapy with ribavirin(RBV) plus Hydroxychloroquine(HCQ). Receives: Drug: Ribavirin; Drug: Hydroxychloroquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy
To evaluate the effect of 16-week combination therapy with RBV plus HCQ following 8 weeks of monotherapy with RBV in HCV-infected patients.
Measured: 24 weeks
Safety: Number of Participants With Adverse Events
Safety was assessed throughout study by collection of adverse event and concomitant medication data, and routine monitoring of lab safety tests, physical exams, ophthalmic examination, vital signs and 12 lead electrocardiograms.
Measured: all 24 weeks
Secondary outcomes (1)
Efficacy
To evaluate the efficacy of 8 weeks monotherapy with RBV in HCV-infected patients.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2013 (estimated)
- Study startApr 2013
- Primary completionApr 2014
- Study completionApr 2014
Why it stopped: due to failure to recruit subjects
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 Hepatitis CStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- BioLineRx, Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Stanislas Pol, MD, Principal investigator, Cochin HospitalMarc Bourliere, MD, Principal investigator, S.Joseph Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01833845
- Sponsor's protocol ID
- BL-8020.01
- Status last verified
- Aug 2014
- First submitted
- 15 Apr 2013
- Last updated
- 28 Aug 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Study to Evaluate the Efficacy, Safety and Tolerability of Ribavirin Monotherapy Followed by Combined Treatment With Ribavirin and Hydroxychloroquine in Patients Infected With Hepatitis C
- ClinicalTrials.gov ID
- NCT01833845
- Acronym / sponsor ID
- BL-8020.01
- Conditions
- Hepatitis C
- Keywords
- HCV, Hepatitis C, Hep-C
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: due to failure to recruit subjects
- Enrolment
- 4 participants (actual)
- Lead sponsor
- BioLineRx, Ltd.Industry (pharma, biotech, devices)
- Study start
- Apr 2013
- Primary completion
- Apr 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 17 Apr 2013 (estimated)
- Results
- Posted 28 Aug 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Proof-of Concept, Open-Label, Two-Stage Study without Direct Individual Benefit The proposed study design consists of two treatment periods and one treatment arm. Treatment Period 1 involves the administration of RBV monotherapy for a period of 8 weeks and Treatment Period 2 involves administration of up to 16 weeks combination therapy with RBV plus HCQ.
Detailed description
Patients who provide their informed consent and conform to all the inclusion and none of the exclusion criteria will be enrolled into the study and will receive RBV monotherapy for 8 weeks. Subjects will receive weight-based doses (1000 mg/day administered BID [twice daily] for subjects ≤ 75 kg and 1200 mg/day administered BID for subjects > 75 kg). Those subjects receiving 1000 mg/day RBV will take 2 tablets of 200 mg/tablet in the morning and 3 tablets in the evening, and those subjects receiving 1200 mg/day RBV will take 3 tablets morning and evening.
During Treatment Period 2, subjects will receive HCQ 575 mg administered as a single tablet once daily (QD), in addition to continuing the same dose of RBV that was administered during Treatment Period 1, as combination therapy for up to 16 weeks.
Subjects will undergo regular blood sampling throughout Treatment Periods 1 and 2 to measure viral response (HCV RNA). Safety will be assessed throughout the study by collection of adverse event (AE) and concomitant medication data, and routine monitoring of laboratory safety tests, vital signs and 12-lead electrocardiograms (ECG).
Subjects will have their viral response tested following 12 weeks of combination therapy; those who show < 1 log decline in viral load during the combination therapy will have the opportunity to withdraw and transfer to standard of care (SoC) treatment following performance of the "End of Study Treatment" visit.
On completion of study treatment, subjects will be allowed to transfer immediately to SoC treatment in order to maximize the benefit of any reduced viral load resulting from combination therapy with RBV plus HCQ. Subjects will attend the clinical site for an "End of Study Treatment" visit within 2 weeks of the final dose of combination treatment with RBV plus HCQ during which they will undergo a final measurement of HCV RNA, safety assessments as described above and a full physical and ophthalmic examination. The "End of Study Treatment" visit may take place on the same day as the final study visit at week 24.
In the event of subjects achieving viral undetectability during combination therapy, the relevant subjects may be administered additional combination therapy to achieve a total of 24 weeks of viral undetectability. If combination dosing with RBV plus HCQ continues for more than 16 weeks, subjects will continue to attend the clinical site and undergo assessment of safety and viral load at the discretion of the Investigator. However, treatment beyond 16 weeks of combination therapy will be considered compassionate use and will not be considered part of the study. In these subjects, the "End of Study Treatment" visit will take place no more than 2 weeks after the Week 24 visit.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ribavirin+HCQ | Experimental | Drug: Ribavirin, Drug: HydroxychloroquineAdministration of RBV monotherapy for a period of 8 weeks following administration of up to 16 weeks combination therapy with ribavirin(RBV) plus Hydroxychloroquine(HCQ). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Male or female, age ≥ 18.
- Subjects diagnosed to have positive HCV antibodies.
- Subject is diagnosed to have detectable HCV RNA by PCR.
- FibroTest or FibroScan or liver biopsy showing a METAVIR score ≤ F2 and/or
- ≤ A2 within 2 years of the screening visit.
Key exclusion criteria (23 listed)
- Contraindication or hypersensitivity to one of the study drugs (HCQ or RBV).
- Patient has anemia (male <13 g/dL; female <12 g/dL), elevated ALT and/or AST >10 x ULN or elevated creatinine (>1.5 mg/dL).
- Concomitant liver disease other than hepatitis C: alcoholic liver disease, autoimmune hepatitis, Wilson's disease, hemochromatosis, alpha-1 antitrypsin deficiency.
- Decompensated cirrhosis (Child Pugh >A).
- Ongoing hepatocellular carcinoma (suggestive imaging study or alpha-fetoprotein (AFP) >50 ng/mL).
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 |
|---|---|---|
| RibavirinAlso: RBVweight-based doses (1000 mg/day administered BID [twice daily] for subjects ≤ 75 kg and 1200 mg/day administered BID for subjects > 75 kg). Those subjects receiving 1000 mg/day RBV will take 2 tablets of 200 mg/tablet in the morning and 3 tablets in the evening, and those subjects receiving 1200 mg/day RBV will take 3 tablets morning and evening. | Drug | Ribavirin+HCQ |
| HydroxychloroquineAlso: HCQsubjects will receive HCQ 575 mg administered as a single tablet once daily (QD) | Drug | Ribavirin+HCQ |
Primary outcome
Efficacy
Time frame: 24 weeks
To evaluate the effect of 16-week combination therapy with RBV plus HCQ following 8 weeks of monotherapy with RBV in HCV-infected patients.
Safety: Number of Participants With Adverse Events
Time frame: all 24 weeks
Safety was assessed throughout study by collection of adverse event and concomitant medication data, and routine monitoring of lab safety tests, physical exams, ophthalmic examination, vital signs and 12 lead electrocardiograms.
1 secondary outcome
Efficacy
Time frame: 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2014.
- 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.
Stanislas Pol, MD principal investigator
Cochin Hospital
Marc Bourliere, MD principal investigator
S.Joseph Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Ribavirin and Hydroxychloroquine in people with Hepatitis C, run by BioLineRx, Ltd. at 2 sites in France.
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 11 inclusion and 23 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: stopped early, as of the sponsor's last update on 28 Aug 2014. 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 France. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 28 Aug 2014). 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?
Efficacy (time frame: 24 weeks). The study lists 2 primary outcomes in all. 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 28 Aug 2014.