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

NCT01567540 | Terminated Phase 1 DMC

• 2 other identifiers: C10-542011-000823-34
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Hepatitis C

Keywords

Chronic Hepatitis C; Interferon protein 10; Chemokine gradients; Sitagliptin

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (5)

• Change in Viral Load as compared to baseline

  week 1, 2, 3 of sitagliptin monotherapy; week 2, 4, 12 of triple therapy

• Metabolic studies: Oral glucose tolerance will be assessed

  baseline, week 1 of sitagliptin monotherapy; week 2 of triple therapy

• Immunologic study

  baseline, week 1 and 3 of sitagliptin monotherapy; week 1, 2, 4, 12 of triple therapy

• Immunologic study

  baseline; week 1 and 3 of sitagliptin monotherapy; week 1, 2, 4, 12 of triple therapy

• Immunologic study

  baseline, week 1 and 3 of sitagliptin monotherapy; week 1, 2, 4, 12 of triple therapy.

Study Arms (1)

DPPIV Inhibition

EXPERIMENTAL

The study includes an initial phase of 3 weeks with administration of sitagliptin (100 mg/d) as monotherapy, followed immediately by 12 weeks of triple therapy (sitagliptin 100 mg/d combined with peg-IFN alfa-2a and ribavirin).

Drug: Sitagliptin

Interventions

Sitagliptin DRUG

100 mg Sitagliptin daily for 15 weeks

DPPIV Inhibition

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead

Study Sites (4)

Centre Hospitalier Victor Dupuy

Argenteuil, 95100, France

Location

Centre Hospitalier Intercommunal Créteil

Créteil, 94010, France

Location

Henri Mondor Hospital

Créteil, 94010, France

Location

Cochin Hospital

Paris, 75014, France

Location

MeSH Terms

Conditions

Hepatitis C; Hepatitis C, Chronic

Interventions

Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases; Hepatitis, Chronic; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Study Officials

• Matthew L. ALBERT, MD, PhD

  Institut National de la Santé Et de la Recherche Médicale, France

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2012
• First Posted: March 30, 2012
• Study Start: March 1, 2013
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: January 20, 2014

Record last verified: 2014-01

Locations

FR (4)