Newcastle Clinical Trials Unit



TRAFIC - Targeting the Rheumatoid Arthritis synovial fibroblast via cyclin dependent kinase inhibition – an early phase trial

Study Stage: Part 1 complete, part 2 in follow-up
Sponsor: The Newcastle upon Tyne Hospitals NHS Foundation Trust
Funder: Medical Research Council: Biomedical Catalyst: Developmental pathway Funding Scheme
Therapeutic area: Musculoskeletal
Type of study: CTIMP

Aim: Part 1: To determine the MTD of seliciclib in participants with active Rheumatoid Arthritis (RA) despite treatment with anti-TNF as either monotherapy or with background conventional disease-modifying anti-rheumatic drugs (DMARDs). Part 2: To assess response to treatment at 12 weeks.

Primary outcome:

Part 1: Identification of Maximum Tolerated Dose of Seliciclib to be used in part 2 as determined by the CRM algorithm developed for this study, with a target Dose Limiting Toxicity probability of 35%; or determination of unacceptable toxicity leading to cessation of trial.

Part 2: Composite response at 12 weeks based on clinical (EULAR and ACR20 response rates), histological (macrophage number in the sub lining layer of synovium) and MRI (Rheumatoid Arthritis MRI Scoring System (RAMRIS)) scores alongside evidence of PD activity.

Population: Adult
Clinical Phase: Ib/IIa (Part 1: Dose escalation design - Part 2: Single arm, single stage)
Design: Adaptive
Setting: Secondary Care
Planned Sample Size: 39 (21 part 1 and 18 part 2)