Background/Purpose: To characterize the safety and efficacy of INCB039110, a novel and selective JAK1 inhibitor, in patients with active RA.

Methods: This phase 2, multicenter study (NCT01626573) was conducted in two parts in the United States. Part 1 consisted of an initial 28-day treatment period in an independent group of patients with active RA and identified a dosing range of INCB039110 that was evaluated in part 2. In part 2, presented here, patients with active RA (≥ 6 tender/≥ 4 swollen joints out of 28 examined) and CRP ≥ 6 mg/L were randomized to placebo (PBO) or INCB039110 at daily oral doses of 100 mg BID, 300 mg QD, 200 mg BID or 600 mg QD. Patients could be on stable doses of methotrexate, hydroxychloroquine, corticosteroids (< 10 mg/day) and/or sulfasalazine. Other concurrent DMARDs/biologics were excluded. The primary analysis was at the end of an 84-day PBO controlled period.

Results: Of the 60 planned patients, 40 patients have completed the Day 84 visit and were included in this analysis. Seven patients discontinued treatment. Mean age across treatment groups was 53.2 yrs and 73% were female. Mean disease duration was 9 yrs. Approximately 90% were on background DMARDs and approximately 33% had been previously treated with biologics.

Response rates at Day 84 for ACR and DAS28 CRP and mean percent change from baseline in DAS28 CRP are shown in the table.

Table. Efficacy parameters at Day 84

Responses were observed as early as the first assessment (14 days), demonstrating a rapid onset of action. Similar ACR responses were achieved with INCB039110 regardless of background therapy or previous biologic experience.

There were no grade 3 or grade 4 AEs and no dose relationship for treatment-related AEs. One patient experienced a grade 2 ALT elevation. One patient experienced an unrelated serious AE of rib fracture. There were no serious or opportunistic infections. A dose-related increase in LDL was noted. There was no change in HDL to LDL ratio.

Conclusion: INCB039110 given once or twice daily over 84 days was generally well tolerated and demonstrated rapid and clinically meaningful responses in patients with active RA.