A clinical study to investigate the safety of multiple doses of DEN-181 in rheumatoid arthritis patients

INTERVENTION: Randomised double blind, placebo‐controlled, single centre,study of three administrations of DEN‐181 at two dose levels (15 active, 5 placebo per dose level). DEN‐181 is a liposomal formulation encapsulating two active pharmaceutical ingredients, calcitriol (0.6 ug/mL) and collagen II peptide (42 ug/mL; 15 amino acid peptide corresponding to collagen II protein 259‐273 (Proline 273 Hydroxyproline substitution). Dose levels will be selected from 100µL, 300uL, or 1000µL DEN‐181 and chosen following the single dose arm of this study. DEN‐181 will be delivered by subcutaneous injection at weekly intervals for three weeks. CONDITION: Rheumatoid Arthritis PRIMARY OUTCOME: Clinical safety observations including changes in: ; Vital signs, Symptom directed physical examination, Adverse events (graded according to Common Terminology Criteria for Adverse Events (CTCAE, Version 4.03), Laboratory abnormalities (Haematology including ESR and Clinical chemistry including CRP in serum samples), Urinalysis ; SECONDARY OUTCOME: Determination of the concentration of calcitriol in plasma samples. Mean changes in DAS28CRPv4 (Disease Activity Score 28 including CRP assessment 4 variable calculation) scoring system. Phenotype of naïve, effector and regulatory T‐cells by flow cytometry. ; Proportion and total number of naïve, effector and regulatory T‐cells by flow cytometry (composite outcome). ; ; INCLUSION CRITERIA: Diagnosis of RA made by a rheumatologist; HLA‐DRB1*0401+, HLA‐DRB1*0101+ or HLA‐DRB1*0401+HLADRB1*0101+ heterozygotes, homozygotes or compound heterozygotes and ACPA+; Treatment with MTX at the same dose for at least 4 weeks prior to planned start of trial treatment; Age 18‐75 years, inclusive; Male or female. Females of child‐bearing potential must agree to use two effective forms of contraception from enrolment to completion of the study; Patients must be informed of the investigational nature of this study and give written informed consent in accordance with the institutional and hospital guidelines; Blood glucose, CBC, haemoglobin, platelets, creatinine, bilirubin, and AST/ALT not greater than 1.5 x out of normal laboratory ranges at entry and clinically insignificant in opinion of investigator; Patients agree to forego vaccinations during the course of the study.