Chronic Hepatitis CPhase 1/2NCT02118012
Evaluation of Safety, Tolerability, and Antiviral Activity of Chlorcyclizine HCl in Patients With Chronic Hepatitis C
A Phase 1/2 study testing Chlorcyclizine HCl and Ribavirin in people with Chronic Hepatitis C, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
Trial summary
Background: Hepatitis C is a liver disease caused by the hepatitis C virus. It is the most common cause of serious liver disease in the United States. Many people have few if any symptoms. It can lead to cirrhosis, which can cause liver failure and cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Hepatitis C
- What is being tested?
- Chlorcyclizine HCl and Ribavirin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Mar 2014to 20 Sep 2016
- 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
- Adults, ages 18 and above;
- Chronic hepatitis C (HCV RNA in serum for more than 6 months);
- HCV RNA in serum at or above 10,000 IU/mL;
- Treatment naive patients defined as individuals whom have never undergone any form of interferon and ribavirin therapy for chronic HCV infection or relapsers defined as reappearance of HCV RNA in serum after treatment (with any form of interferon and ribavirin therapy) was discontinued and an end-of-treatment response was achieved;
- No major contraindications to agents being used (chlorcyclizine HCl and ribavirin);
- Females of childbearing potential must have a negative serum or urine pregnancy test result (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours before the first dose of study drug;
- Women of childbearing potential and men, participants and partners, must use highly effective methods of birth control to minimize the risk of pregnancy and must follow instructions for birth control for the entire duration of the study including a minimum of 24 weeks after the last dose of ribavirin. Two forms of birth control are required from the time of screening throughout the duration of the on-treatment study period and for at least 24 weeks after the last dose of ribavirin. Examples of effective birth control include: condom with spermicide; diaphragm with spermicide; cervical cap with spermicide; female condom; intrauterine devices (IUDs); vasectomy in men;
Who cannot join
- Liver or any other organ transplant (including hematopoietic stem cell transplants) other than cornea and hair;
- Current or known history of cancer (except in situ carcinoma of the cervix or adequately treated basal or squamous cell carcinoma of the skin) within 5 years prior to enrollment;
- Documented or suspected HCC, as evidenced by previously obtained imaging studies or liver biopsy (or on a screening imaging study/liver biopsy if this was performed);
- Evidence of decompensated liver disease including, but not limited to, bilirubin >4 mg/dL, albumin <3.0 gm/dL, prothrombin time >2 sec prolonged or a history or presence of ascites, bleeding varices, or hepatic encephalopathy. Patients with ALT levels >500 U/L will not be enrolled but may be followed until three determinations are below this level;
- Evidence of a medical condition contributing to chronic liver disease other than chronic HCV infection (such as, but not limited to: acute hepatitis C infection, hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures);
- History of chronic hepatitis B virus (HBV) as documented by HBV serologies (eg, HBsAg-seropositive). Subjects with resolved HBV infection may participate (eg, HBsAb-seropositive with concurrent HBsAg-seronegative);
Show all 22Show fewer
- Any prior exposure to direct-acting antiviral therapies for chronic HCV infection;
- History of HIV infection;
- History of hemoglobinopathies (eg. thalassemia major or sickle cell anemia), diagnoses associated with an increased baseline risk for anemia (eg, spherocytosis), hemolytic anemia, or diseases in which anemia would be medically problematic, or hemophilia;
- Confirmed, uncontrolled hypertension (any screening systolic blood pressure greater than or equal to 160 mmHg or diastolic blood pressure greater than or equal to 100 mmHg should be excluded unless discussed with the central medical monitor);
- Any other medical and/or social reason, including active substance abuse as defined by DSM-IV, Diagnostic Criteria for Drug and Alcohol Abuse, which in the opinion of the investigator would make the candidate inappropriate for participation in this study;
- Significant systemic or major illnesses other than liver disease, including, but not limited to, clinically significant emphysema or chronic bronchitis, symptomatic benign prostatic hypertrophy, glaucoma, gastrointestinal motility related illnesses, congestive heart failure, renal failure (eGFR <50 mL/min), and active coronary artery disease;
- Significant prior history suggestive of cardiovascular instability, including but not limited to evidence of significant myocardial ischemia, unstable re-entry phenomena, other significant dysrhythmias and/or uncontrolled hypertension;
- Inability to tolerate oral medication;
- For relapsers: exposure to interferon based therapy with ribavirin within 12 weeks prior to screening;
- Allergy or hypersensitivity to chlorcyclizine HCl or ribavirin;
- Any known contraindication to ribavirin, not otherwise specified;
- Inability to refrain from operating heavy machinery while on therapy;
- Breastfeeding women;
- Inability to understand or sign informed consent;
- Active use of chlorcyclizine HCl or another piperazine class antihistamine within 6 months of enrollment;
- Inability to abstain from piperazine class antihistamines during enrollment in the clinical trial period.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Evaluation of Safety, Tolerability, and Antiviral Activity of Chlorcyclizine HCl Alone or in Combination With Ribavirin in Patients With Chronic Hepatitis C
Background:
- Hepatitis C is a liver disease caused by the hepatitis C virus. It is the most common cause of serious liver disease in the United States. Many people have few if any symptoms. It can lead to cirrhosis, which can cause liver failure and cancer. Researchers want to study how a medicine called chlorcyclizine works in patients with hepatitis C. They want to see if it can be used to treat hepatitis C alone or when used with the standard hepatitis C treatment drug ribavirin.
Read more
Objectives:
- To see if chlorcyclizine can be used to treat hepatitis C alone or in combination with the drug ribavirin.
Eligibility:
- Adults with chronic hepatitis C who either have never been treated for it or have relapsed after prior treatment.
Design:
- Participants will be screened with medical history, physical exam, blood and urine tests, and a questionnaire. They will also have an ultrasound of their abdomen and electrocardiogram. Some of these tests will be repeated throughout the study.
- Participants will spend 3 days as an inpatient to be monitored while starting study drug. They will be assigned randomly to a group and will begin taking the study drug. Blood will be taken frequently.
- Group I will take the study drug twice a day for 28 days.
- Group II will take the study drug twice a day and ribavirin twice a day for 28 days.
- Participants will visit the clinic every 7 days for 28 days.
- After participants stop taking the study drug, they will have 5 follow-up visits over 3 months.
Read the detailed description
Up to 50 patients with chronic hepatitis C, who are treatment na(SqrRoot) ve or relapsers to any interferon/ribavirin regimen will be enrolled into this pilot study evaluating chlorcyclizine HCl with or without ribavirin (RBV) as antiviral therapy. Adult patients (greater than or equal to18 years of age) with evidence of active chronic hepatitis C infection (all genotypes) with detectable HCV RNA in serum >10,000 IU/mL without contraindications to chlorcyclizine HCl or ribavirin or evidence/history of hepatic decompensation will be enrolled. Patients will be monitored for at least two months with regular testing for ALT and HCV RNA quantitative levels before treatment and will undergo admission to start therapy, which includes a thorough medical evaluation and timed blood sampling. Patients will be randomized to one of two treatment groups; one with chlorcyclizine HCl (75 mg twice daily) and the other with RBV+ chlorcyclizine HCl (75 mg twice daily). For all genotypes, RBV will be dosed based on weight (1000 mg daily <75 kg and 1200 mg daily greater than or equal to 75 kg). At each clinic visit, patients will be questioned about side effects and symptoms, undergo a focused physical examination, and have blood taken for complete blood counts, HCV RNA, PT/INR and routine liver tests (ALT, AST, alkaline phosphatase, direct and total bilirubin, and albumin). At the end of 28 days of treatment, patients will undergo a repeat thorough medical evaluation inclusive of a complete physical exam, symptom scale evaluation, complete blood counts, routine liver tests, and HCV serology panels. The primary endpoint of therapy will be a decline in quantitative HCV RNA viral levels after 28 days of treatment as compared to baseline viral titers and between groups. Several secondary endpoints will be measured, including side effects of therapy, ALT levels, quantification of chlorcyclizine HCl and its metabolites in serum, and quality of life. Therapy will be stopped for intolerance to RBV and/or chlorcyclizine HCl (which will be carefully defined).
- Conditions
- Chronic Hepatitis C
- Being tested
- Chlorcyclizine HCl, Ribavirin
- Keywords
- Chlorcyclizine HCL, Direct Acting Antivirals, Ribavirin, Chronic Hepatitis C
- Medical subject headings
- Hepatitis C, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Chlorcyclizine HClDrug
Also called CCZ
Chlorcyclizine HCl (75 mg twice daily)
RibavirinDrug
Also called RBV
RBV was dosed via a weight-based regimen of 1000 mg daily<75 kg and 1200 mg daily ≥75 kg.
| Study group | Role | What they receive |
|---|---|---|
| Chlorcyclizine and RBV | Active comparator | Chlorcyclizine HCl and Ribavirin Receives: Drug: Chlorcyclizine HCl; Drug: Ribavirin |
| Chlorcyclizine HCl only | Active comparator | Chlorcyclizine HCl only Receives: Drug: Chlorcyclizine HCl |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Serum HCV RNA Viral Titer From Baseline to 28 Days
Measured: Baseline and 28 days
Number of Participants Who Tolerated the Drug at the Prescribed Dose for the Duration of Therapy
Measured: 28 days
Secondary outcomes (2)
Change in Alanine Aminotransferase (ALT) Levels From Baseline to 28 Days
Measured: Baseline and 28 days
Maximum Chlorcyclizine HCL Weeks 1-4
Chlorcyclizine HCL concentration was measured once a week in the morning. This outcome is the maximum over the four weeks.
Measured: Weeks 1-4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2014 (estimated)
- Study start20 Mar 2014
- Primary completion20 Mar 2014
- Study completion20 Sep 2016
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Hepatitis CStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Christopher Koh, M.D., Principal investigator, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02118012
- Sponsor's protocol ID
- 140084
- Other IDs
- 14-DK-0084
- Status last verified
- 17 Sep 2019
- First submitted
- 16 Apr 2014
- Last updated
- 9 Jun 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Koh C, Dubey P, Han MAT, Walter PJ, Garraffo HM, Surana P, Southall NT, Borochov N, Uprichard SL, Cotler SJ, Etzion O, Heller T, Dahari H, Liang TJ. A randomized, proof-of-concept clinical trial on repurposing chlorcyclizine for the treatment of chronic hepatitis C. Antiviral Res. 2019 Mar;163:149-155. doi: 10.1016/j.antiviral.2019.01.017. Epub 2019 Jan 31.
PubMed 30711416
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Safety, Tolerability, and Antiviral Activity of Chlorcyclizine HCl Alone or in Combination With Ribavirin in Patients With Chronic Hepatitis C
- ClinicalTrials.gov ID
- NCT02118012
- Acronym / sponsor ID
- 140084
- Conditions
- Chronic Hepatitis C
- Keywords
- Chlorcyclizine HCL, Direct Acting Antivirals, Ribavirin, Chronic Hepatitis C
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Study start
- 20 Mar 2014
- Primary completion
- 20 Mar 2014 (actual)
- Study completion
- 20 Sep 2016 (actual)
- First posted
- 21 Apr 2014 (estimated)
- Results
- Posted 9 Jun 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Hepatitis C is a liver disease caused by the hepatitis C virus. It is the most common cause of serious liver disease in the United States. Many people have few if any symptoms. It can lead to cirrhosis, which can cause liver failure and cancer. Researchers want to study how a medicine called chlorcyclizine works in patients with hepatitis C. They want to see if it can be used to treat hepatitis C alone or when used with the standard hepatitis C treatment drug ribavirin.
Objectives:
- To see if chlorcyclizine can be used to treat hepatitis C alone or in combination with the drug ribavirin.
Eligibility:
- Adults with chronic hepatitis C who either have never been treated for it or have relapsed after prior treatment.
Design:
- Participants will be screened with medical history, physical exam, blood and urine tests, and a questionnaire. They will also have an ultrasound of their abdomen and electrocardiogram. Some of these tests will be repeated throughout the study.
- Participants will spend 3 days as an inpatient to be monitored while starting study drug. They will be assigned randomly to a group and will begin taking the study drug. Blood will be taken frequently.
- Group I will take the study drug twice a day for 28 days.
- Group II will take the study drug twice a day and ribavirin twice a day for 28 days.
- Participants will visit the clinic every 7 days for 28 days.
- After participants stop taking the study drug, they will have 5 follow-up visits over 3 months.
Detailed description
Up to 50 patients with chronic hepatitis C, who are treatment na(SqrRoot) ve or relapsers to any interferon/ribavirin regimen will be enrolled into this pilot study evaluating chlorcyclizine HCl with or without ribavirin (RBV) as antiviral therapy. Adult patients (greater than or equal to18 years of age) with evidence of active chronic hepatitis C infection (all genotypes) with detectable HCV RNA in serum >10,000 IU/mL without contraindications to chlorcyclizine HCl or ribavirin or evidence/history of hepatic decompensation will be enrolled. Patients will be monitored for at least two months with regular testing for ALT and HCV RNA quantitative levels before treatment and will undergo admission to start therapy, which includes a thorough medical evaluation and timed blood sampling. Patients will be randomized to one of two treatment groups; one with chlorcyclizine HCl (75 mg twice daily) and the other with RBV+ chlorcyclizine HCl (75 mg twice daily). For all genotypes, RBV will be dosed based on weight (1000 mg daily <75 kg and 1200 mg daily greater than or equal to 75 kg). At each clinic visit, patients will be questioned about side effects and symptoms, undergo a focused physical examination, and have blood taken for complete blood counts, HCV RNA, PT/INR and routine liver tests (ALT, AST, alkaline phosphatase, direct and total bilirubin, and albumin). At the end of 28 days of treatment, patients will undergo a repeat thorough medical evaluation inclusive of a complete physical exam, symptom scale evaluation, complete blood counts, routine liver tests, and HCV serology panels. The primary endpoint of therapy will be a decline in quantitative HCV RNA viral levels after 28 days of treatment as compared to baseline viral titers and between groups. Several secondary endpoints will be measured, including side effects of therapy, ALT levels, quantification of chlorcyclizine HCl and its metabolites in serum, and quality of life. Therapy will be stopped for intolerance to RBV and/or chlorcyclizine HCl (which will be carefully defined).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Chlorcyclizine and RBV | Active comparator | Drug: Chlorcyclizine HCl, Drug: RibavirinChlorcyclizine HCl and Ribavirin |
| Chlorcyclizine HCl only | Active comparator | Drug: Chlorcyclizine HClChlorcyclizine HCl only |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Adults, ages 18 and above;
- Chronic hepatitis C (HCV RNA in serum for more than 6 months);
- HCV RNA in serum at or above 10,000 IU/mL;
- Treatment naive patients defined as individuals whom have never undergone any form of interferon and ribavirin therapy for chronic HCV infection or relapsers defined as reappearance of HCV RNA in serum after treatment (with any form of interferon and ribavirin therapy) was discontinued and an end-of-treatment response was achieved;
- No major contraindications to agents being used (chlorcyclizine HCl and ribavirin);
Key exclusion criteria (22 listed)
- Liver or any other organ transplant (including hematopoietic stem cell transplants) other than cornea and hair;
- Current or known history of cancer (except in situ carcinoma of the cervix or adequately treated basal or squamous cell carcinoma of the skin) within 5 years prior to enrollment;
- Documented or suspected HCC, as evidenced by previously obtained imaging studies or liver biopsy (or on a screening imaging study/liver biopsy if this was performed);
- Evidence of decompensated liver disease including, but not limited to, bilirubin >4 mg/dL, albumin <3.0 gm/dL, prothrombin time >2 sec prolonged or a history or presence of ascites, bleeding varices, or hepatic encephalopathy. Patients with ALT levels >500 U/L will not be enrolled but may be followed until three determinations are below this level;
- Evidence of a medical condition contributing to chronic liver disease other than chronic HCV infection (such as, but not limited to: acute hepatitis C infection, hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures);
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 |
|---|---|---|
| Chlorcyclizine HClAlso: CCZChlorcyclizine HCl (75 mg twice daily) | Drug | Chlorcyclizine HCl only, Chlorcyclizine and RBV |
| RibavirinAlso: RBVRBV was dosed via a weight-based regimen of 1000 mg daily<75 kg and 1200 mg daily ≥75 kg. | Drug | Chlorcyclizine and RBV |
Primary outcome
Change in Serum HCV RNA Viral Titer From Baseline to 28 Days
Time frame: Baseline and 28 days
Number of Participants Who Tolerated the Drug at the Prescribed Dose for the Duration of Therapy
Time frame: 28 days
2 secondary outcomes
Change in Alanine Aminotransferase (ALT) Levels From Baseline to 28 Days
Time frame: Baseline and 28 days
Maximum Chlorcyclizine HCL Weeks 1-4
Time frame: Weeks 1-4
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 30711416Koh C, Dubey P, Han MAT, Walter PJ, Garraffo HM, Surana P, Southall NT, Borochov N, Uprichard SL, Cotler SJ, Etzion O, Heller T, Dahari H, Liang TJ. A randomized, proof-of-concept clinical trial on repurposing chlorcyclizine for the treatment of chronic hepatitis C. Antiviral Res. 2019 Mar;163:149-155. doi: 10.1016/j.antiviral.2019.01.017. Epub 2019 Jan 31.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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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.
Christopher Koh, M.D. principal investigator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
1 site 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 Chlorcyclizine HCl and Ribavirin in people with Chronic Hepatitis C, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
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 22 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 9 Jun 2020. 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 United States. 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 9 Jun 2020). 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?
Change in Serum HCV RNA Viral Titer From Baseline to 28 Days (time frame: Baseline and 28 days). 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?
On the ClinicalTrials.gov record for NCT02118012, 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 9 Jun 2020.