A randomized, double-blind, placebo-controlled study of secukinumab to demonstrate the efficacy at 24 weeks and to assess the safety, tolerability and long term efficacy up to 2 years in patients with active rheumatoid arthritis who have an inadequate response to anti-TNF(RegisteredTM) agents
This study uses a double-blind, randomized, parallel-group, placebo-controlled design.
a screening (SCR) period running 4 weeks before randomization will be used to assess eligibility followed by a treatment period of 2 years.
at baseline (BSL), patients whose eligibility is confirmed will be randomized to one of three treatment groups:
* Group 1: secukinumab i.v. (10 mg/kg) at BSL, Weeks 2 and 4 then secukinumab 75 mg
s.c. starting at Week 8 and injected every 4 weeks
* Group 2: secukinumab i.v. (10 mg/kg) at BSL, Weeks 2 and 4 then secukinumab 150 mg s.c. starting at Week 8 and injected every 4 weeks
* Group 3:placebo i.v. at BSL, Weeks 2 and 4 then placebo s.c. starting at Week 8 and
injected every 4 weeks
at Week 24, efficacy of secukinumab treatment will be assessed based on an aCR20
at Week 16, subjects will be classified as responders ([GreaterThanorequalTo]20% improvement from baseline in both tender and swollen joint counts) or non-responders and will be re-assigned/re-randomized at Week to receive double-blind treatment up to 2 years, as follows
* Subjects on secukinumab 75 mg s.c. (Group 1) will continue to receive secukinumab 75
mg s.c. every 4 weeks regardless of responder status
* Subjects on secukinumab 150 mg s.c. (Group 2) will continue to receive secukinumab 150 mg s.c. every 4 weeks regardless of responder status
* Subjects on secukinumab placebo (Group 3) who are non-responders will be re-randomized to receive secukinumab 75 mg s.c. or 150 mg s.c. (1:1) every 4 weeks
* Subjects on secukinumab placebo (Group 3) who are responders will continue to receive secukinumab placebo until Week 24.
at Week 24, these subjects will be re-randomized to receive secukinumab 75 mg s.c. or 150 mg s.c. (1:1) every 4 weeks regardless of responder status Rescue medication will not be allowed until Week 24. However, subjects who are deemed not to be benefiting from the study drug by the investigator or for any reason on their own accord will be free to discontinue participation in the study at any time. Subjects who complete the 2 year study may be eligible to enter a planned extension study. a Follow-up visit is to be done 12 weeks after last study treatment administration for subjects who terminated the study early or for subjects who completed the study but do not enter the extension study.
The available physical, chemical and pharmaceutical properties and formulations were updated in iB edition 13 to include liquid in vial formulation (LiVi). it is a colorless to slightly yellowish solution (125mg/5.0ml) in a 6 ml colorless hydrolytic type 1 glass vial with fluoropolymer-coated grey rubber stopper and aluminum cap seal with flip-off disk cap.
novartis will be discontinuing the development program for Secukinumab (ain457) in rheumatoid arthritis (Ra). This decision is based on the efficacy results from the phase iii study Cain457F2309 (nuRTuRe 1) in Ra patients who failed anti-TnF therapy.
The decision to discontinue the program in Ra does not impact ongoing programs with secukinumab in psoriasis, psoriatic arthritis and ankylsoing spondylitis. The trial suggests that the pathogensis of Ra may be less dependent on iL-17 than in these other indications.
no safety issue was identified in the study; overall safety was similar to other phase iii studies in psoriasis, psoriatic arthritis and ankylosing spondylitis.
Based on the decision to discontinue the develoopment program for secukinumab in Ra, the following trials will be terminated as defined in the protocol section [Quote]early Study Termination[Quote]:
Cain457F2302 (Section 5.5.12), Cain457F2302e1 (Section 5.4.12), Cain457F2309e1 (Section 5.5.12), Cain457F2311 (Section 5.5.12). Cain457f2309 will not be terminated early but will be completed as planned as all patients have completed the treatment phase of the study.
1. Patient must be able to understand and communicate with the investigator and comply with the requirements of the study and must give a written, signed and dated informed consent before any study assessment is performed
2. Male or non-pregnant, non-lactating female patients at least 18 years of age
3. Presence of RA classified by ACR 2010 revised criteria (see Appendix 2) for at least 3 months before screening
4. At Baseline: Disease activity criteria defined by >=6 tender joints out of 68 and >= 6 swollen joints out of 66 WITH at least 1 of the following at screening:
* Anti-CCP antibodies positive OR
* Rheumatoid Factor positive AND WITH at least 1 of the following at screening:
* hsCRP >= 10 mg/L OR
* ESR >=28 mm/1st hr
5. Patients must have been taking at least one anti-TNF-(RegisteredTM) agent such as etanercept, adalimumab, infliximab, certolizumab or golimumab given at an approved dose for at least 3 months before randomization and have experienced an inadequate response to treatment or have been intolerant to at least one administration of an anti-TNF-(RegisteredTM) agent
6. Patients who have been on anti-TNF-(RegisteredTM) agent will be allowed entry into study after appropriate wash-out period prior to randomization:
a. 4 weeks for Enbrel(RegisteredTM) (etanercept) x with a terminal half-life of 102 (+ or -) 30 hours (s.c. route)
b. 8 weeks or longer for Remicade(RegisteredTM) (infliximab) x with a terminal half-life of 8.0-9.5 days (i.v. infusion)
c. 10 weeks or longer for Humira(RegisteredTM) (adalimumab) x with a terminal half-life of 10-20 days (average 2 weeks) (s.c. route)
d. 10 weeks for Simponi(RegisteredTM) (golimumab) x with a terminal half-life of 11-14 days
e. 10 weeks for Cimzia(RegisteredTM) (certolizumab) x with a terminal half-life of 14 days
7. Patients must be taking MTX for at least 3 months before randomization and have to be on a stable dose at least 4 weeks before randomization (7.5 to 25 mg/week (For Japan only: 6 to 25 mg/week))
8. Patients must be taking folic acid supplementation before randomization
9. Patients who were taking other DMARDs (in combination with or without MTX) will be allowed entry into study after appropriate washout period (except for MTX) prior to baseline: 28 days, except for leflunomide, which has to be discontinued for 8 weeks prior to baseline unless a cholestyramine washout has been performed
10. Patients taking systemic corticosteroids have to be on a stable dose of <=10 mg/d prednisone or equivalent for at least 4 weeks before randomization
11. Patients who are regularly taking NSAIDs (COX-1 or COX-2 inhibitors) are required to be on a stable dose for at least 4 weeks before randomization