A Pilot Study Evaluating Safety of Sitagliptin Combined With Peg-IFN Alfa-2a + Ribavirin in Chronic Hepatitis C Patients

Hepatitis C Clinical Trial

Official title:

A Pilot Study to Evaluate the Clinical and Biological Tolerance of Sitagliptin With Pegylated Interferon alfa2a Plus Ribavirin Combination Therapy in Chronic Hepatitis C Patients

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01567540
• Other study ID #: C10-54
• Secondary ID: 2011-000823-34
• Status: Terminated
• Phase: Phase 1
• First received: March 2, 2012
• Last updated: January 17, 2014
• Start date: March 2013
• Est. completion date: January 2014

Study information

• Verified date: January 2014
• Source: Institut National de la Santé Et de la Recherche Médicale, France
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

Hepatitis C infection is a major public health problem with nearly 175 million infected individuals worldwide. Although cure is possible, only 20-40% of patients spontaneously resolve infection and 40-80% of chronically infected patients (numbers vary depending on viral genotype) that receive pegylated-interferon-alfa2a/ribavirin therapy clear the virus and are sustained virologic responders (SVR). Still for many, the virus manages to circumvent natural immunity and current therapeutic strategies, resulting in significant morbidity and mortality.

To better define the distinct clinical outcomes of HCV infection many investigators have performed candidate molecules screens or transcriptional profiling in order to identify correlates of viral clearance. One molecule that has gained significant attention is CXCL10 (also known as interferon-gamma induced protein-10 or IP-10) as an important negative prognostic biomarker. Given that CXCL10 is produced by hepatocytes and mediates chemo-attraction of activated lymphocytes expressing the CXCL10-receptor, CXCR3, it is counter-intuitive as to why this chemokine correlates with therapeutic non-responsiveness.

The investigators hypothesized and have now demonstrated that CXCL10 is being cleaved in situ, resulting in the generation of an antagonist form of the chemokine. Based on the use of specific inhibitors, the investigators now propose to test whether protection of the agonist form of CXCL10 will increase responsiveness to peg-IFN-alfa2 / ribavirin therapy. This can be achieved using DPPIV inhibitors, targeting the enzyme responsible for N-terminal truncation of CXCL10. If safety is confirmed, the efficacy of DPPIV-inhibition in HCV patients will be tested in future trials that examine potential clearance benefits.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Age between 18 and 70 years

• For women, effective contraception during the trial and a negative pregnancy test (urine) before enrollment

• Patients naïve to prior hepatitis C treatment

• Confirmed HCV infection, based on the presence of HCV antibodies and plasma viremia allowing a measure of the circulating viral load

• Infection with HCV genotype 1 or 4

• Intent of treatment Alfa2 pegylated IFN-/ ribavirin

Exclusion Criteria:

• HBV Infection

• HIV Infection

• Severe anemia (Hb <7-8 g / dl)

• Renal failure (creatinine clearance <60 ml / min)

• Taking digoxin within 6 months of starting treatment.

• Taking immunosuppressants within 6 months of starting treatment

• History of serious hypersensitivity reaction (such as anaphylactic shock or angioedema) to sitagliptin

• Patients with type I and II diabetes

• Pregnancy or absence of effective contraception

• A person deprived of liberty by judicial or administrative decision

• Living conditions-suggesting an inability to track all scheduled visits by the protocol

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• Sitagliptin
100 mg Sitagliptin daily for 15 weeks

Locations

Country	Name	City	State
France	Centre Hospitalier Victor Dupuy	Argenteuil
France	Centre Hospitalier Intercommunal Créteil	Créteil
France	Henri Mondor Hospital	Créteil
France	Cochin Hospital	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Institut National de la Santé Et de la Recherche Médicale, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety (Number of adverse events, Toxicity grade > 3)		After Day 1 until the end of the trial, i.e. a duration of 15 weeks for each patient	Yes
Secondary	Change in Viral Load as compared to baseline		week 1, 2, 3 of sitagliptin monotherapy; week 2, 4, 12 of triple therapy	No
Secondary	Metabolic studies: Oral glucose tolerance will be assessed		baseline, week 1 of sitagliptin monotherapy; week 2 of triple therapy	No
Secondary	Immunologic study	Monitoring the short and long form of IP-10 as compared to the total plasma concentration (three distinct ELISA assays).	baseline, week 1 and 3 of sitagliptin monotherapy; week 1, 2, 4, 12 of triple therapy	No
Secondary	Immunologic study	Plasma concentration and activity of DPPIV (measured using an ELISA and a luciferase-based bioassay, respectively).	baseline; week 1 and 3 of sitagliptin monotherapy; week 1, 2, 4, 12 of triple therapy	No
Secondary	Immunologic study	Frequency of CXCR3+ cells in circulation (monitored by FACS).	baseline, week 1 and 3 of sitagliptin monotherapy; week 1, 2, 4, 12 of triple therapy.	No