Chronic Hepatitis C Virus InfectionPhase 1NCT00255359
Safety, Tolerability and Efficacy of XTL 2125 in HCV-Infected Patients Who Are Interferon-Alpha Non-Responders or Relapsers
A Phase 1 study testing XTL-2125 in people with Chronic Hepatitis C Virus Infection, run by Hadassah Medical Organization at 1 site in Israel.
Trial summary
The study will be a randomized, double blind, placebo controlled, dose rising study in Interferon alpha (IFN-alpha) non-responder HCV infected patients or HCV patients who have relapsed following IFN-alpha therapy. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Chronic Hepatitis C Virus Infection
- What is being tested?
- XTL-2125
- How many people
- 60 participants
- Where
- 1 siteIsrael
- Study dates
- Feb 2006to Nov 2007
- Phase
- Phase 1
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must understand and be willing to give written informed consent prior to any study procedures or evaluations and be willing to adhere to all study schedules and requirements.
- Adults 18 to 70 years of age.
- Documented history of positive HCV serology.
- Compensated liver disease as defined by the following at screening: PT greater or equal to 60%, INR < 1.5, serum albumin greater or equal 3.4 g%, and serum bilirubin < 2 mg% (unless dx of Gilbert's Syndrome).
- Serum HCV RNA greater or equal 100,000 IU/mL at screening.
- Patients who were treated and did not respond to IFN-alpha therapy or who withdrew from this therapy within 30 days prior to screening.
Show all 10Show fewer
- Patients who had completed a fully prescribed course of an approved IFN alpha -based treatment and relapsed following the end of the treatment.
- Patients must be sterile or infertile or use an approved method of contraception from the time that the first dose of study medication is taken until three months following study completion or discontinuation.
- Screening labs as follows: platelet count greater or equal 120,000/mm3; ANC greater or equal 1000/mm3; hemoglobin greater or equal 11.0 g/dL for females and greater or equal 12.0 g/dL for males; serum ALT within normal limits or < 5 x ULN.
- Alpha fetoprotein <25 microg/L at screening.
Who cannot join
- Any history of significant cardiac, renal, neurologic, metabolic, pulmonary, gastrointestinal, hematologic abnormality, chronic hepatic disease other than hepatitis C or any other disease which in the judgment of the investigator would interfere with the study or confound the results.
- Patients with positive HIV serology or positive HBsAg at screening.
- Patients who were not treated previously with the current approved therapy against HCV.
- Patients who have received any previous treatment for HCV infection other than an approved regimen of IFN alpha and ribavirin within 30 days prior to screening.
- Patients with decompensated liver disease or evidence of advanced liver disease such as the presence of ascites, bleeding varices or hepatic encephalopathy.
- Female patients who are breastfeeding or have a positive pregnancy test at screening or at any time during the study.
Show all 11Show fewer
- History of alcohol or drug abuse within 6 months of screening.
- Patients who have a positive urine drug screen for substances of abuse (benzodiazepine, THC, opiates, amphetamines, cocaine) at the screening.
- Patients with poor venous access
- History or evidence of hepatocellular carcinoma (HCC).
- Use of prescription or non-prescription drugs that are known to be metabolized in the liver and can potentially interfere with the study medication (such as Marcolide antibiotics, azole antifungals, warfarin, carbamazepine, cyclosporine, midazolam, phenytoin, valporic acid, chlorpromazine, rifampin, quinidine, diazepam and digoxin) 90 days prior to screening.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Multicenter, Randomized, Double-Blind, Placebo Controlled, Dose Escalation Study of the Safety and Efficacy of XTL 2125 in Adult HCV-Infected Patients With Compensated Liver Disease, Who Are Interferon-Alpha Non-Responders or Have Relapsed From Interferon-Alpha Therapy
The study will be a randomized, double blind, placebo controlled, dose rising study in Interferon alpha (IFN-alpha) non-responder HCV infected patients or HCV patients who have relapsed following IFN-alpha therapy. Eligible subjects must have compensated liver disease and serum HCV RNA concentrations above 100,000 IU/mL at screening. The study will include both a single dose period for the evaluation of acute toxicity and single dose pharmacokinetics and a consecutive multi-dose period for the determination of longer-term safety, multiple-dose pharmacokinetics and antiviral activity. The objectives of this study are to evaluate the safety, tolerability, and antiviral activity of escalating single and multiple doses of XTL 2125 in patients with chronic hepatitis C virus infection and to assess the single- and multiple-dose pharmacokinetics of XTL 2125
Read the detailed description
The study will be of a randomized, double blind, placebo controlled, multicenter design with sequential ascending doses of XTL 2125 in HCV-infected patients with compensated liver disease who did not respond to IFN-alpha therapy or relapsed following this therapy.
This study will include both a single dose session and a multiple dose session. In the single dose session, patients will be randomized to receive a single oral dose of either XTL 2125 or placebo on Day 1, in a dose-escalating design, followed by a multiple dose session that will start on day 8 and will continue for 14 days. The same patients will receive XTL 2125 three times daily at the same dose administered in the single dose session.
The following doses will be administered to groups of 8 patients each: 10 mg, 25 mg, 50 mg, 150 mg, 300 mg and 450 mg. Within each group, 6 subjects will receive XTL 2125 and 2 subjects will receive placebo. No patient will be enrolled in more than one dose level. Doses should be administered one hour before meals with 240 cc water.
Additional patients may be enrolled at previous or intermediate doses to obtain additional safety or pharmacokinetic/pharmacodynamic data and to more accurately define the Maximum Tolerated Dose (MTD).
The MTD will be defined as the last dose level that is successfully administered with a decision to escalate to the next level. If the decision not to escalate to the next level is made then a cohort that receives XTL 2125 at a dose half-way between the last tolerated dose and the non-tolerated dose may be enrolled at the discretion of the Sponsor. If this dose is successfully administered without violating the dose escalation rules, then this interim dose will be considered the MTD.
Six dose cohorts will be prospectively indicated, although additional cohorts may be scheduled at intermediate doses if warranted by the data.
- Conditions
- Chronic Hepatitis C Virus Infection
- Being tested
- XTL-2125
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
XTL-2125Drug
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety:
• adverse events, serious adverse events
• laboratory abnormalities by highest toxicity grade
• laboratory abnormalities by largest increase in toxicity grade from baseline
Efficacy:
• Median change from baseline in serum HCV RNA (log10 IU/mL) at day 22.
• Median maximum change from baseline at any time between Day 8 and Day 22.
• Median change from baseline in serum ALT at day 22.
• Percent of patients within each cohort with serum HCV RNA declining at least a 1 log10 from baseline at any assessment between Day 8 and 22.
• AUC using the trapezoidal rule, minus baseline for serum HCV RNA (in the log10 scale) through day 22 (defined as DAVG22).
• Median rate of decline in serum HCV RNA (log10 IU/mL/day) through day 22.
• Median rate of change in serum HCV RNA (log10 IU/mL/day) from day 22 (after the last administration) through day 50 (rebound).
• Median change from day 22 (after the last administration) in serum HCV RNA (log10 IU/mL) at day 50 (rebound).
• Descriptive analysis of changes in the HCV genome (NS5B region coding for RNA dependent RNA polymerase) that may be associated with two weeks of
XTL 2125 monotherapy.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2005 (estimated)
- Study startFeb 2006
- Study completionNov 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Hepatitis C Virus InfectionStudies of the same condition, open and under way.
- More trials run by Hadassah Medical OrganizationThe 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hadassah Medical Organization
- Sponsor type
- University, hospital or other
- Collaborators
- XTL Biopharmaceuticals
- Investigators
- Eithan Galun, MD, Principal investigator, Hadassah Medical OrganizationShlomo Dagan, PhD, Study director, XTL Biopharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00255359
- Sponsor's protocol ID
- 200517-HMO-CTIL
- Status last verified
- Nov 2007
- First submitted
- 16 Nov 2005
- Last updated
- 6 Nov 2007
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2007. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Double-Blind, Placebo Controlled, Dose Escalation Study of the Safety and Efficacy of XTL 2125 in Adult HCV-Infected Patients With Compensated Liver Disease, Who Are Interferon-Alpha Non-Responders or Have Relapsed From Interferon-Alpha Therapy
- ClinicalTrials.gov ID
- NCT00255359
- Acronym / sponsor ID
- 200517-HMO-CTIL
- Conditions
- Chronic Hepatitis C Virus Infection
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Hadassah Medical OrganizationUniversity, hospital or other
- Collaborators
- XTL Biopharmaceuticals
- Study start
- Feb 2006
- Study completion
- Nov 2007
- First posted
- 18 Nov 2005 (estimated)
- 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.
The study will be a randomized, double blind, placebo controlled, dose rising study in Interferon alpha (IFN-alpha) non-responder HCV infected patients or HCV patients who have relapsed following IFN-alpha therapy. Eligible subjects must have compensated liver disease and serum HCV RNA concentrations above 100,000 IU/mL at screening. The study will include both a single dose period for the evaluation of acute toxicity and single dose pharmacokinetics and a consecutive multi-dose period for the determination of longer-term safety, multiple-dose pharmacokinetics and antiviral activity. The objectives of this study are to evaluate the safety, tolerability, and antiviral activity of escalating single and multiple doses of XTL 2125 in patients with chronic hepatitis C virus infection and to assess the single- and multiple-dose pharmacokinetics of XTL 2125
Detailed description
The study will be of a randomized, double blind, placebo controlled, multicenter design with sequential ascending doses of XTL 2125 in HCV-infected patients with compensated liver disease who did not respond to IFN-alpha therapy or relapsed following this therapy.
This study will include both a single dose session and a multiple dose session. In the single dose session, patients will be randomized to receive a single oral dose of either XTL 2125 or placebo on Day 1, in a dose-escalating design, followed by a multiple dose session that will start on day 8 and will continue for 14 days. The same patients will receive XTL 2125 three times daily at the same dose administered in the single dose session.
The following doses will be administered to groups of 8 patients each: 10 mg, 25 mg, 50 mg, 150 mg, 300 mg and 450 mg. Within each group, 6 subjects will receive XTL 2125 and 2 subjects will receive placebo. No patient will be enrolled in more than one dose level. Doses should be administered one hour before meals with 240 cc water.
Additional patients may be enrolled at previous or intermediate doses to obtain additional safety or pharmacokinetic/pharmacodynamic data and to more accurately define the Maximum Tolerated Dose (MTD).
The MTD will be defined as the last dose level that is successfully administered with a decision to escalate to the next level. If the decision not to escalate to the next level is made then a cohort that receives XTL 2125 at a dose half-way between the last tolerated dose and the non-tolerated dose may be enrolled at the discretion of the Sponsor. If this dose is successfully administered without violating the dose escalation rules, then this interim dose will be considered the MTD.
Six dose cohorts will be prospectively indicated, although additional cohorts may be scheduled at intermediate doses if warranted by the data.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patients must understand and be willing to give written informed consent prior to any study procedures or evaluations and be willing to adhere to all study schedules and requirements.
- Adults 18 to 70 years of age.
- Documented history of positive HCV serology.
- Compensated liver disease as defined by the following at screening: PT greater or equal to 60%, INR < 1.5, serum albumin greater or equal 3.4 g%, and serum bilirubin < 2 mg% (unless dx of Gilbert's Syndrome).
- Serum HCV RNA greater or equal 100,000 IU/mL at screening.
Key exclusion criteria (11 listed)
- Any history of significant cardiac, renal, neurologic, metabolic, pulmonary, gastrointestinal, hematologic abnormality, chronic hepatic disease other than hepatitis C or any other disease which in the judgment of the investigator would interfere with the study or confound the results.
- Patients with positive HIV serology or positive HBsAg at screening.
- Patients who were not treated previously with the current approved therapy against HCV.
- Patients who have received any previous treatment for HCV infection other than an approved regimen of IFN alpha and ribavirin within 30 days prior to screening.
- Patients with decompensated liver disease or evidence of advanced liver disease such as the presence of ascites, bleeding varices or hepatic encephalopathy.
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 |
|---|---|---|
| XTL-2125 | Drug | – |
Primary outcome
Safety:
• adverse events, serious adverse events
• laboratory abnormalities by highest toxicity grade
• laboratory abnormalities by largest increase in toxicity grade from baseline
Efficacy:
• Median change from baseline in serum HCV RNA (log10 IU/mL) at day 22.
• Median maximum change from baseline at any time between Day 8 and Day 22.
• Median change from baseline in serum ALT at day 22.
• Percent of patients within each cohort with serum HCV RNA declining at least a 1 log10 from baseline at any assessment between Day 8 and 22.
• AUC using the trapezoidal rule, minus baseline for serum HCV RNA (in the log10 scale) through day 22 (defined as DAVG22).
• Median rate of decline in serum HCV RNA (log10 IU/mL/day) through day 22.
• Median rate of change in serum HCV RNA (log10 IU/mL/day) from day 22 (after the last administration) through day 50 (rebound).
• Median change from day 22 (after the last administration) in serum HCV RNA (log10 IU/mL) at day 50 (rebound).
• Descriptive analysis of changes in the HCV genome (NS5B region coding for RNA dependent RNA polymerase) that may be associated with two weeks of
XTL 2125 monotherapy.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2007.
Related trials for Chronic Hepatitis C Virus Infection
RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Active, not recruitingPhase 4
People With CHC Who Achieved a Sustained Virological Response Following Therapy With Direct Acting Antiviral Agents
Diabetes Mellitus, Hepatitis C, Chronic
RecruitingObservational study
"Constitution of a Biological Collection to Establish Preclinical Translational Models for the Study of Tumors and Chronic Liver Diseases".
Chronic Liver Disease and Cirrhosis, Liver Cancer
Active, not recruitingPhase 4
Sofosbuvir/Velpatasvir Treatment of Chronic Hepatitis C During Pregnancy
Hepatitis C, Chronic, Pregnancy; Infection
Enrolling by invitationObservational study
Comparative Autoantibody and Immunologic Cell Marker Study
Autoimmune Diseases, Lupus Erythematosus, Systemic
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.
Eithan Galun, MD principal investigator
Hadassah Medical Organization
Shlomo Dagan, PhD study director
XTL Biopharmaceuticals
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing XTL-2125 in people with Chronic Hepatitis C Virus Infection, run by Hadassah Medical Organization at 1 site in Israel.
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 10 inclusion and 11 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: withdrawn, as of the sponsor's last update on 6 Nov 2007. 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 Israel. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Safety:. The study lists 15 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 6 Nov 2007.