Presentation abstract of PFE competitor's phase IIb:
abstractsonline.com
The Oral Jak Inhibitor CP-690,550 (CP) in Combination with Methotrexate (MTX) is Efficacious, Safe and Well Tolerated in Patients with Active Rheumatoid Arthiritis (RA) with an Inadequate Response to Methotrexate Alone
Purpose:
To compare the efficacy, safety and tolerability of 6 dose levels of oral CP vs placebo for the treatment of RA in patients (pts) with active RA on stable background MTX, who had an inadequate response to MTX alone; to characterize the dose-response profile of CP.
Methods:
In this 6-month, double-blind, placebo-controlled Phase 2B study, pts with active disease (=6 tender joints, =6 swollen joints and CRP >7 mg/dL or ESR > ULN) were randomized equally to 1, 3, 5, 10, 15 mg BID, or 20 mg QD, of CP or placebo. Pts receiving CP 1 mg, 3 mg BID, 20 mg QD, or placebo who did not achieve =20% reduction from baseline in swollen and tender joint counts at Wk 12 were reassigned to CP 5 mg BID for the remainder of the study. The primary outcome was ACR response rate at Wk-12. Efficacy and safety assessments were carried out at Wks 2, 4, 6, 8, 12, 16, 20, and 24. Data are presented from an interim analysis at Wk-12; efficacy data are through Wk-12 (or early termination), safety data are through Wk-24.
Results:
509 pts (80% women) were randomized. Mean ages across dose groups were 50.8-56.1 yrs (range 18-81 yrs). Mean disease duration ranged from 7.1-11.7 yrs; 69%-89% were rheumatoid factor positive. At baseline, mean tender joint counts ranged from 21.49-24.71, swollen joint counts from 14.04-16.52 and HAQ-DI from 1.20-1.57. Mean baseline DAS28-3 (CRP) scores ranged from 5.14-5.49.
The most frequently reported treatment-emergent AEs (all causality) were: nausea 2.4%; headache 2.2% and increased ALT 2.0%. Serious AEs ranged from 1-8% in the CP dose groups with none in the placebo arm. 5 serious infections were reported, with no dose-related pattern.
Minor dose-related changes in hemoglobin (Hb) were seen; only 2 pts experienced Hb drops >3 g/dL below baseline (1 pt each on placebo and CP 10 mg BID) and no pts’ neutrophil count fell below 500/µL. Dose-dependent increases in LDL, HDL and total cholesterol were observed, which appeared to plateau between Wks 6 and 12. Reversible ALT increases of >3x the ULN were seen in 5 pts receiving CP 15 mg BID and in one pt in each of CP 10 mg BID, 20 mg QD and placebo.
Conclusions:
Doses of CP 3 mg BID and higher were efficacious vs placebo. Tolerability, AEs and some changes in laboratory values were dose dependent. A range of doses appears suitable to evaluate further in Phase 3 studies.
(For the % responders at Week 12, see table in the link) |
