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Eli Lilly and Company announced the presentation of 12-week results from a Phase IIb study of baricitinib, formerly LY3009104 (INCB28050), an orally available janus kinase (JAK) inhibitor, in patients with active rheumatoid arthritis (RA). The results were presented as a late-breaking oral presentation at the European League Against Rheumatism's (EULAR) Annual European Congress of Rheumatology [EULAR abstract LB0005: 12-Week Results of a Phase IIb Dose-Ranging Study of LY3009104 (INCB028050), an Oral JAK1/JAK2 Inhibitor, in Combination with Traditional DMARDs in Patients with Rheumatoid Arthritis].
The Phase IIb randomized double-blind, placebo-controlled, dose-ranging study, known as JADA, involved a total of 301 patients with active RA on stable doses of methotrexate. Patients were randomized to receive either placebo or one of four once-daily doses of baricitinib (1 mg, 2 mg, 4 mg or 8 mg) for 12 weeks.
Primary Endpoint Achieved:
The Phase IIb trial achieved the primary endpoint by demonstrating a statistically significant difference in the American College of Rheumatology 20 (ACR20) response between the combined 4 mg and 8 mg baricitinib groups (76 percent) compared with placebo (41 percent) after 12 weeks of treatment (p < 0.001). Statistically significant improvement was observed at the first assessment point after two weeks of treatment and was sustained through week 12.
Summary of Secondary Endpoints:
A statistically significant difference in response for the ACR20, ACR50 and ACR70 secondary endpoints was observed with the 1 mg, 4 mg and 8 mg dose groups compared with placebo.
ACR20
8 mg: 78 percent (p < 0.001)
4 mg: 75 percent (p < 0.001)
2 mg: 54 percent (not significant)
1 mg: 57 percent (p < 0.05)
Placebo: 41 percent
ACR50
8 mg: 40 percent (p < 0.001)
4 mg: 35 percent (p < 0.001)
2 mg: 17 percent (not significant)
1 mg: 31 percent (p < 0.05)
Placebo: 10 percent
ACR70
8 mg: 20 percent (p < 0.001)
4 mg: 23 percent (p < 0.001)
2 mg: 8 percent (not significant)
1 mg: 12 percent (p < 0.05)
Placebo: 2 percent
Safety Results:
The most common treatment-emergent adverse event class was infections, with a similar rate observed among patients in the placebo group (12 percent) and patients receiving baricitinib (14 percent). One patient in the placebo group was diagnosed with an opportunistic infection of toxocariasis. No deaths or opportunistic infections occurred in the active treatment groups.
There were seven serious adverse events reported in six patients (two events in the placebo group, four in the 2 mg group and one in the 8 mg group). Dose-dependent changes in laboratory tests (hemoglobin, neutrophil, serum creatinine, LDL and HDL) were observed, with greater changes being observed in the 8 mg baricitinib group.
Trial Design and Status:
This Phase IIb trial consists of three parts: Part A, Part B and an open-label extension. Part A was randomized, double-blind and placebo-controlled. Patients randomized to baricitinib received one of four doses administered once daily for 12 weeks.
In Part B, patients initially randomized to placebo or the 1 mg baricitinib dose were re-randomized to receive either 4 mg once daily or 2 mg twice daily for 12 weeks. Patients initially randomized to the 2 mg, 4 mg and 8 mg doses continued therapy for an additional 12 weeks.
Patients completing Part B were eligible to continue in an open-label extension arm on either the 4 mg or 8 mg once daily doses of baricitinib for 52 additional weeks.
Part B of the study has completed and data analysis is underway. Patients are continuing to participate in the open-label long-term extension of the trial.
About Baricitinib:
Baricitinib is an orally administered selective JAK1 and JAK2 inhibitor that is JAK3-sparing. Currently, baricitinib is in Phase II development as a treatment for rheumatoid arthritis and psoriasis.
Source: lilly.com
The Phase IIb randomized double-blind, placebo-controlled, dose-ranging study, known as JADA, involved a total of 301 patients with active RA on stable doses of methotrexate. Patients were randomized to receive either placebo or one of four once-daily doses of baricitinib (1 mg, 2 mg, 4 mg or 8 mg) for 12 weeks.
Primary Endpoint Achieved:
The Phase IIb trial achieved the primary endpoint by demonstrating a statistically significant difference in the American College of Rheumatology 20 (ACR20) response between the combined 4 mg and 8 mg baricitinib groups (76 percent) compared with placebo (41 percent) after 12 weeks of treatment (p < 0.001). Statistically significant improvement was observed at the first assessment point after two weeks of treatment and was sustained through week 12.
Summary of Secondary Endpoints:
A statistically significant difference in response for the ACR20, ACR50 and ACR70 secondary endpoints was observed with the 1 mg, 4 mg and 8 mg dose groups compared with placebo.
ACR20
8 mg: 78 percent (p < 0.001)
4 mg: 75 percent (p < 0.001)
2 mg: 54 percent (not significant)
1 mg: 57 percent (p < 0.05)
Placebo: 41 percent
ACR50
8 mg: 40 percent (p < 0.001)
4 mg: 35 percent (p < 0.001)
2 mg: 17 percent (not significant)
1 mg: 31 percent (p < 0.05)
Placebo: 10 percent
ACR70
8 mg: 20 percent (p < 0.001)
4 mg: 23 percent (p < 0.001)
2 mg: 8 percent (not significant)
1 mg: 12 percent (p < 0.05)
Placebo: 2 percent
Safety Results:
The most common treatment-emergent adverse event class was infections, with a similar rate observed among patients in the placebo group (12 percent) and patients receiving baricitinib (14 percent). One patient in the placebo group was diagnosed with an opportunistic infection of toxocariasis. No deaths or opportunistic infections occurred in the active treatment groups.
There were seven serious adverse events reported in six patients (two events in the placebo group, four in the 2 mg group and one in the 8 mg group). Dose-dependent changes in laboratory tests (hemoglobin, neutrophil, serum creatinine, LDL and HDL) were observed, with greater changes being observed in the 8 mg baricitinib group.
Trial Design and Status:
This Phase IIb trial consists of three parts: Part A, Part B and an open-label extension. Part A was randomized, double-blind and placebo-controlled. Patients randomized to baricitinib received one of four doses administered once daily for 12 weeks.
In Part B, patients initially randomized to placebo or the 1 mg baricitinib dose were re-randomized to receive either 4 mg once daily or 2 mg twice daily for 12 weeks. Patients initially randomized to the 2 mg, 4 mg and 8 mg doses continued therapy for an additional 12 weeks.
Patients completing Part B were eligible to continue in an open-label extension arm on either the 4 mg or 8 mg once daily doses of baricitinib for 52 additional weeks.
Part B of the study has completed and data analysis is underway. Patients are continuing to participate in the open-label long-term extension of the trial.
About Baricitinib:
Baricitinib is an orally administered selective JAK1 and JAK2 inhibitor that is JAK3-sparing. Currently, baricitinib is in Phase II development as a treatment for rheumatoid arthritis and psoriasis.
Source: lilly.com