NCT01567540

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

Terminated Phase 1 Last updated 17 January 2014

What this trial tests

Phase 1 trial testing Sitagliptin in Hepatitis C in 3 participants. Terminated before completion.

Timeline

1 March 2013

Primary endpoint
1 January 2014

1 January 2014

Quick facts

Lead sponsor	Institut National de la Santé Et de la Recherche Médicale, France
Phase	Phase 1
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	3
Start date	1 March 2013
Primary completion	1 January 2014
Estimated completion	1 January 2014
Sites	4 locations across France

Drugs / interventions tested

• Sitagliptin (SITAGLIPTIN) — full drug profile →

Conditions studied

• Hepatitis C — all drugs for Hepatitis C →

Sponsor

Institut National de la Santé Et de la Recherche Médicale, France — full company profile →

Who can join

Adults 18 to 70, any sex, with Hepatitis C. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Safety (Number of adverse events, Toxicity grade > 3)
  Time frame: After Day 1 until the end of the trial, i.e. a duration of 15 weeks for each patient

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Inhibition of DPP4 activity in humans establishes its in vivo role in CXCL10 post-translational modification: prospective placebo-controlled clinical studies.
   Decalf J, Tarbell KV, Casrouge A, Price JD, et al · · 2016 · cited 43× · PMID 27137491 · DOI 10.15252/emmm.201506145
2. Classifying Clinical Trial Eligibility Criteria to Facilitate Phased Cohort Identification Using Clinical Data Repositories.
   Wang AY, Lancaster WJ, Wyatt MC, Rasmussen LV, et al · · 2017 · cited 8× · PMID 29854246