A Multicenter, Parallel-group Study of Long-term Safety and Efficacy of CNTO 136 (sirukumab) for Rheumatoid Arthritis in Subjects Completing Treatment in CNTO136ARA3002 and CNTO136ARA3003
- Clements University Hospital
- Parkland Health & Hospital System
- UT Southwestern-Clinical Translational Research Center (CTRC)
Andreas Reimold, M.D.
1. Main study:
Subjects will become eligible to participate in the Long Term extension (LTe) study when they have completed participation in studies CnTo136aRa3002 (3002) (104 weeks) or CnTo136aRa3003 (3003) (52 weeks). The purpose of the LTe study is to evaluate the safety, efficacy, and pharmacologic effects of sirukumab for a minimum duration of 1 additional year and a maximum total duration of approximately 5 years across the combined protocols 3002 (2 years) or 3003 (1 year) + 3004 (1 to 4 years) [?] maximum of 5 years treatment).
During the Week 104 visit in 3002 or the Week 52 visit in 3003, subjects will sign the informed consent form to enter study 3004. as a result, the Week 104 visit in study 3002 and the Week 52 visit in study 3003 will correspond to the Week 0 visit in the 3004 study.
The 2 sirukumab doses are:
* 100 mg q2 weeks
* 50 mg q4 weeks. To maintain the blind and reduce potential bias, a blinded matching placebo SC injections will be administered at Weeks 2, 6, and q4 weeks until the study becomes open-label and placebo injections will be discontinued.
after a minimum of 1 year treatment in 3004 for subjects from study 3002, or a minimum of 2 years of treatment in 3004 for subjects from 3003, and after sirukumab is approved for the treatment of Ra in the subject's country of residence, the Sponsor may no longer offer study treatment in 3004 for those specific subjects. at that point the subject will have the opportunity to discuss treatment options with their treating physician.
The maximum duration of participation in the study is 208 weeks, followed by approximately 16 weeks of safety and efficacy follow-up after the administration of the final study agent injection of sirukumab.
Study treatment will remain blinded in 3004 until the following 3 conditions have been met: the Week 52 Database Lock (DBL) occurs in study 3002, the Week 24 DBL occurs in study 3003, and the last autoinjector (ai) usability substudy subject completes the Week 16 visit or terminates from the study. Thereafter treatment in study 3004 becomes open-label, and placebo injections are discontinued in the SC sirukumab 50 mg treatment group.
The number of subjects with each of the following long-term safety events through the end of the study: cardiovascular, malignancies, serious infections, and gastrointestinal perforations will be summarized.
no hypothesis testing will be performed.
Major Secondary endpoint:
Laboratory parameters of interest (neutrophils, platelets, hepatobiliary parameters, and lipid parameters) will be observed. Toxicity grade will be summarized by treatment group over time through the end of the study.
The PFS-ai usability sub-study contained within the 3004 study is a multicenter. approximately 100 subjects in english-speaking countries who have entered study 3004 and meet sub-study entry criteria will be enrolled in the PFS-ai sub-study. eligible patients will sign the substudy consent on Week 0 visit in the 3004 study.
The PFS-ai's performance is expected to be the same regardless of study agent dose (placebo, sirukumab 50 mg, or sirukumab 100 mg). The overall duration of this sub-study of 3004 is 16 weeks. The sub-study visit schedule is aligned with the main study schedule, so that following the completion of the PFS-ai sub-study, subjects will continue on in the main 3004 study.
The primary endpoint is the number and proportion of subjects who are able to successfully self administer their second observed dose as measured by completing the 3 instructions for use iFu steps.
Major Secondary endpoints
* number and proportion of subjects who are able to successfully self-administer their first and second observed doses as measured by completing the 3 essential iFu steps
Each potential subject must satisfy all of the following criteria to be enrolled in the study. Each
1. Have completed the final study agent administrations in the primary study (Week 104 injection in CNTO136ARA3002 or Week 52 injection in CNTO136ARA3003) including all other assessments required for these visits. The subject will then be deemed to have completed participation in those studies and will be eligible to enroll in this long-term extension study.
2. Sign an informed consent form (ICF) indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
3. Sign an informed consent form (ICF) for pharmacogenetics research in order to participate in the optional pharmacogenetics component of this study, where local regulations permit. Refusal to give consent for this component does not exclude a subject from participation in this clinical study.
2. Auto-injector Sub-study:
To be eligible for the sub-study, subjects must meet all of the following criteria:
1. Have completed participation in studies CNTO136ARA3002 or CNTO136ARA3003 and are enrolled in study CNTO136ARA3004.
2. Sign an informed consent indicating that they understand the purpose of and procedures required for the sub-study and are willing to participate.
3. Be assessed by the investigator or delegate as competent and be willing and able to self administer study agent.
4. Be able to understand written and spoken English.
5. Be willing and able to use an eDiary to complete dosing assessments using a telephone or
computer to enter information.