A randomised placebo-controlled study to investigate GNbAC1 an anti-HERV-W-Env monoclonal antibody in patients with recent onset of type 1 diabetes : rationale and design

Abstract

AIMS : Human endogenous retroviruses (HERVs) elements, remnants of ancestral viral genomic insertions, are emerging targets in several autoimmune diseases. In type 1 diabetes (T1D) patients, the envelope protein of HERV-W (HERV-W-Env) is detected in 70% of sera and is found expressed by acinar cells in 75% of T1D pancreata. HERV-W-Env pathogenic properties include inhibition of insulin secretion by pancreatic beta cells, and hyperglycemia associated with decreased levels of insulin in a transgenic mouse model, suggesting the involvement of HERV-W-Env in T1D pathogenesis. GNbAC1, a humanised monoclonal antibody targeting specifically HERV-W-Env is tested for the first time in T1D patients. METHOD/DESIGN : This trial is a randomised placebo controlled 2-arm study with the objective of showing the safety and pharmacodynamics response of GNbAC1 in T1D patients. Sixty T1D patients are planned to be included. GNbAC1 will be tested versus placebo at the dose of 6 mg/kg administered intravenously; 6 drug administrations will be performed at 4-week intervals. The primary endpoint will record adverse events, physical examination and vital signs as well as clinical laboratory data. Secondary endpoints will be: glycated haemoglobin blood levels; C-peptide levels up to 2 hours after mixed meal tolerance test; fasting and postprandial blood glucose; change from baseline in percentage of subjects not requiring insulin; daily use of insulin. T1D and autoimmune related antibodies will be assessed. CONCLUSIONS : This first safety and pharmacodynamics study of the monoclonal antibody GNbAC1 in T1D patients, if positive, may open the door for the development of an innovative non-immunomodulatory disease modifying drug for T1D. REGISTRATION : clinicalTrials.gov Identifier: NCT03179423