Chronic Hepatitis C InfectionPhase 1/2NCT01835938
Clinical Investigation of Erlotinib as an HCV Entry Inhibitor
A Phase 1/2 study testing 1- Erlotinib in people with Chronic Hepatitis C Infection and HCV Genotype 1b, run by University Hospital, Strasbourg, France at 1 site in France.
Trial summary
Chronic Hepatitis C Virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma world-wide. Current combination therapy of pegylated interferon-alfa, ribavirin and protease inhibitors is limited by resistance and substantial side effects. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Chronic Hepatitis C Infection, HCV Genotype 1b
- What is being tested?
- 1- Erlotinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteFrance
- Study dates
- May 2013to May 2015
- Phase
- Phase 1/2
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Chronic genotype 1b hepatitis C infection with detectable HCV RNA (> 1x104 UI/mL)
- Naïve, relapser or non-responder to interferon with or without ribavirin
- Weight > 45kg, BMI between 18 and 25 Kg/m2 who had a liver biopsy or liver FibroScan eliminating the presence of cirrhosis in the year before enrollment,
- Non-smoker or occasional smoker ( ie < 3 cig/day)
Who cannot join
- HIV or HBV infection
- Cirrhosis or Liver decompensation
- Chronic liver disease non related to HCV
Trial locations and contacts
1 site in 1 country.
France1 site
Service d'Hépatogastroentérologie, NHC1, place de l'hôpital
Strasbourg, Alsace, BP n°426
Pr. Michel DOFFOEL, MD, PhD
About this study
Official title: Dose Finding and Early Efficacy Study of Erlotinib in Treatment of Chronic Hepatitis C Virus infection_proof of Concept Study
Chronic Hepatitis C Virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma world-wide. Current combination therapy of pegylated interferon-alfa, ribavirin and protease inhibitors is limited by resistance and substantial side effects.
The investigators identified epidermal growth factor receptor (EGFR) as host factor for HCV infection. Inhibition of kinase function of EGFR by approved inhibitor Erlotinib (TarcevaTM) broadly inhibits HCV infection of all major genotypes including viral escape variants resistant to host immune responses.
Read more
Completed preclinical proof-of-concept studies in HCV cell culture and animal model systems demonstrate that inhibition of EGFR function by Erlotinib constitutes a novel antiviral approach for prevention and treatment of HCV infection (European patent application EP 08 305 604.4, Filing date: September 26, 2008; Inserm, Paris, France and Lupberger et al. Nature Medicine 2011).
Since Erlotinib (TarcevaTM) is an established approved drug for cancer treatment and has a well characterized safety profile in humans, the aim of the study is to investigate the safety, efficacy and pharmacokinetics of Erlotinib, a first-in-class entry inhibitor, for treatment of HCV infection in a randomized placebo-controlled double blind clinical trial in patients chronically infected with HCV. Following completion, this trial will set the stage for a further investigation of entry inhibitors as antivirals in combination with standard of care or direct antivirals such as HCV protease inhibitors. Thus, this randomized clinical trial will be an important step in the development of novel urgently needed antiviral therapies overcoming resistance.
- Conditions
- Chronic Hepatitis C Infection, HCV Genotype 1b
- Being tested
- 1- Erlotinib, placebo
- Keywords
- Hepatitis C Virus infection, entry inhibitor, kinase inhibitor
- Medical subject headings
- Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
1- ErlotinibDrug
- Erlotinib 50 mg tablet by mouth every day for 14 days,
- Erlotinib 100 mg tablet by mouth every day for 14 days,
- Erlotinib 150 mg tablet by mouth every day for 14 days,
placeboDrug
- Placebo 50 mg tablet by mouth every day for 14 days,
- Placebo 100 mg tablet by mouth every day for 14 days,
- Placebo 150 mg tablet by mouth every day for 14 days,
| Study group | Role | What they receive |
|---|---|---|
| 1- Erlotinib | Experimental | Erlotinib is a first class HCV entry inhibitor. In this study, Erlotinib will be administered in escalating doses in sequential patient cohorts for 14 days as follows:
* Dose level (DL) 1 = 50 mg / day,
* Dose level (DL) 2 = 100 mg / day, and
* Dose level (DL) 3 = 150 mg / day .
Each Dose Level (DL) includes 4 patients (3 patients treated with Erlotinib and one patient treated with the Placebo). Dose escalation will proceed to the subsequent DL in the absence of DLT (dose-limiting toxicity) in 2 patients receiving Erlotinib. Receives: Drug: 1- Erlotinib |
| placebo | Placebo comparator | Not described Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of virologic response and short-term safety of Erlotinib in patients infected with HCV genotype 1b
Determination of the recommended dose on the end point of dise-limiting toxicity (DLT), establishment of the maximum-tolerated dose (MTD), and response rate defined as a reduction of at least 1 log10 HCV RNA Levels after the last dose of study drug.
Measured: 14-day assessment study
Secondary outcomes (1)
Assessment of pharmacokinetics of Erlotinib in HCV-infected patients
- Evaluate the pharmacokinetics (AUC, Cmax) of Erlotinib.
Measured: 14-day assessment study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2013 (estimated)
- Study startMay 2013
- Primary completionMay 2015 (estimated)
- Study completionMay 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Hepatitis C InfectionStudies of the same condition, open and under way.
- More trials run by University Hospital, Strasbourg, FranceThe 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
- Factorial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Strasbourg, France
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Dr Samira Fafi-Kremer, Pharma D, PhD, Study director, Laboratoire de Virologie PTM- Nouvel Hôpital CivilHôpitaux Universitaires de StrasbourgDr Catherine Mutter, MD, Study chair, Centre d'investigation Clinique -P1002Nouvel Hôpital CivilHôpitaux Universitaires de StrasbourgDr François Habersetzer, MD, PhD, Study chair, Service d'Hépato-Gastro-Entérologie - Nouvel Hôpital CivilHôpitaux Universitaires de StrasbourgDr. Thomas BAUMERT, MD, PhD, Study director, Service d'Hépatogastroentérologie, NHC1, place de l'hôpital - BP n°42667091 STRASBOURG CEDEX
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01835938
- Sponsor's protocol ID
- 5189
- Status last verified
- Jun 2014
- First submitted
- 9 Apr 2013
- Last updated
- 17 Jun 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose Finding and Early Efficacy Study of Erlotinib in Treatment of Chronic Hepatitis C Virus infection_proof of Concept Study
- ClinicalTrials.gov ID
- NCT01835938
- Acronym / sponsor ID
- 5189
- Conditions
- Chronic Hepatitis C Infection, HCV Genotype 1b
- Keywords
- Hepatitis C Virus infection, entry inhibitor, kinase inhibitor
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- University Hospital, Strasbourg, FranceUniversity, hospital or other
- Study start
- May 2013
- Primary completion
- May 2015 (estimated)
- Study completion
- May 2015 (estimated)
- First posted
- 19 Apr 2013 (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.
Chronic Hepatitis C Virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma world-wide. Current combination therapy of pegylated interferon-alfa, ribavirin and protease inhibitors is limited by resistance and substantial side effects.
The investigators identified epidermal growth factor receptor (EGFR) as host factor for HCV infection. Inhibition of kinase function of EGFR by approved inhibitor Erlotinib (TarcevaTM) broadly inhibits HCV infection of all major genotypes including viral escape variants resistant to host immune responses.
Completed preclinical proof-of-concept studies in HCV cell culture and animal model systems demonstrate that inhibition of EGFR function by Erlotinib constitutes a novel antiviral approach for prevention and treatment of HCV infection (European patent application EP 08 305 604.4, Filing date: September 26, 2008; Inserm, Paris, France and Lupberger et al. Nature Medicine 2011).
Since Erlotinib (TarcevaTM) is an established approved drug for cancer treatment and has a well characterized safety profile in humans, the aim of the study is to investigate the safety, efficacy and pharmacokinetics of Erlotinib, a first-in-class entry inhibitor, for treatment of HCV infection in a randomized placebo-controlled double blind clinical trial in patients chronically infected with HCV. Following completion, this trial will set the stage for a further investigation of entry inhibitors as antivirals in combination with standard of care or direct antivirals such as HCV protease inhibitors. Thus, this randomized clinical trial will be an important step in the development of novel urgently needed antiviral therapies overcoming resistance.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1- Erlotinib | Experimental | Drug: 1- ErlotinibErlotinib is a first class HCV entry inhibitor. In this study, Erlotinib will be administered in escalating doses in sequential patient cohorts for 14 days as follows: * Dose level (DL) 1 = 50 mg / day, * Dose level (DL) 2 = 100 mg / day, and * Dose level (DL) 3 = 150 mg / day . Each Dose Level (DL) includes 4 patients (3 patients treated with Erlotinib and one patient treated with the Placebo). Dose escalation will proceed to the subsequent DL in the absence of DLT (dose-limiting toxicity) in 2 patients receiving Erlotinib. |
| placebo | Placebo comparator | Drug: placebo |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Chronic genotype 1b hepatitis C infection with detectable HCV RNA (> 1x104 UI/mL)
- Naïve, relapser or non-responder to interferon with or without ribavirin
- Weight > 45kg, BMI between 18 and 25 Kg/m2 who had a liver biopsy or liver FibroScan eliminating the presence of cirrhosis in the year before enrollment,
- Non-smoker or occasional smoker ( ie < 3 cig/day)
Key exclusion criteria (3 listed)
- HIV or HBV infection
- Cirrhosis or Liver decompensation
- Chronic liver disease non related to HCV
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 |
|---|---|---|
| 1- Erlotinib* Erlotinib 50 mg tablet by mouth every day for 14 days, * Erlotinib 100 mg tablet by mouth every day for 14 days, * Erlotinib 150 mg tablet by mouth every day for 14 days, | Drug | 1- Erlotinib |
| placebo* Placebo 50 mg tablet by mouth every day for 14 days, * Placebo 100 mg tablet by mouth every day for 14 days, * Placebo 150 mg tablet by mouth every day for 14 days, | Drug | placebo |
Primary outcome
Assessment of virologic response and short-term safety of Erlotinib in patients infected with HCV genotype 1b
Time frame: 14-day assessment study
Determination of the recommended dose on the end point of dise-limiting toxicity (DLT), establishment of the maximum-tolerated dose (MTD), and response rate defined as a reduction of at least 1 log10 HCV RNA Levels after the last dose of study drug.
1 secondary outcome
Assessment of pharmacokinetics of Erlotinib in HCV-infected patients
Time frame: 14-day assessment study
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2014.
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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.
Dr Samira Fafi-Kremer, Pharma D, PhD study director
Laboratoire de Virologie PTM- Nouvel Hôpital CivilHôpitaux Universitaires de Strasbourg
Dr Catherine Mutter, MD study chair
Centre d'investigation Clinique -P1002Nouvel Hôpital CivilHôpitaux Universitaires de Strasbourg
Dr François Habersetzer, MD, PhD study chair
Service d'Hépato-Gastro-Entérologie - Nouvel Hôpital CivilHôpitaux Universitaires de Strasbourg
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 1- Erlotinib in people with Chronic Hepatitis C Infection and HCV Genotype 1b, run by University Hospital, Strasbourg, France at 1 site 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 4 inclusion and 3 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 17 Jun 2014. 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 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. Some participants in this study may receive a placebo. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Pr. Michel Doffoel, MD, PhD (03 69 55 04 82, michel.doffoel@chru-strasbourg.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of virologic response and short-term safety of Erlotinib in patients infected with HCV genotype 1b (time frame: 14-day assessment study). 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 17 Jun 2014.