Efficacy and Safety of Olokizumab in Subjects With Moderately to Severely Active Rheumatoid Arthritis
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Olokizumab 64 mg SC q4w; Olokizumab 64 mg SC q2w; Concomitant treatment
Intervention description: 160 mg/mL sterile solution for SC injection in a 2 mL clear Type I glass vial with target volume of 0.4 mL or in the pre-filled syringe (PFS).PFS is composed of a 1 mL clear Type I glass barrel vial with target volume of 0.4 mL.; 160 mg/mL sterile solution for SC injection in a 2 mL clear Type I glass vial with target volume of 0.4 mL or in the pre-filled syringe (PFS). PFS is composed of a 1 mL clear Type I glass barrel vial with target volume of 0.4 mL.; Methotrexate 15 to 25 mg/week (or ≥ 10 mg/week if there was documented intolerance to higher doses). (Subject maintained their stable dose and route (oral, SC, or IM) during the core study and for ≥ 12 additional weeks of OLE.)
Folic acid ≥ 5 mg per week or equivalent
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 2106.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Rheumatoid Arthritis; moderate; severe; subcutaneous; Olokizumab; open-label

Summary:

      The primary objective of this study was to evaluate the long-term safety and tolerability of
      olokizumab (OKZ) 64 mg administered subcutaneously (SC) once every 2 weeks (q2w) or once
      every 4 weeks (q4w) in subjects with moderately to severely active rheumatoid arthritis (RA)
      who previously had completed 24 weeks of double-blind treatment in Study CREDO 1, 2 or 3
      (core studies). The long-term efficacy, immunogenicity, the physical function and quality of
      life of subjects received long-term treatment with OKZ were assessed as well.
    

Eligibility criteria:

        Inclusion Criteria:

        Subjects may be enrolled in the study only if they meet all of the following criteria:

          1. Subject must be willing and able to sign informed consent

          2. Subject must have completed the 24-week double-blind Treatment Period in 1 of the 3
             core studies (CL04041022, CL04041023, or CL04041025).

          3. Subject must have maintained their stable dose (and route) of MTX 15 to 25 mg/week (or
             ≥ 10 mg/week if there is documented intolerance to higher doses) during the core study
             and plan to maintain the same dose and route of administration for ≥ 12 additional
             weeks

          4. Subjects must be willing to take folic acid or equivalent throughout the study.

        Exclusion Criteria:

          1. Subject with any medically important condition in the core study (e.g., clinically
             significant laboratory values, frequent Adverse events (AEs) or serious adverse events
             (SAEs), infection SAEs, and/or other concurrent severe and/or uncontrolled medical
             condition) which would make this subject unsuitable for inclusion in the open-label
             extension (OLE) study in the Investigator's judgement.

          2. Subject has evidence of active tuberculosis (TB)

          3. Subject with a positive or repeated indeterminate interferon-gamma release assay
             (IGRA) result at Week 22 of the core study

             - Subjects may be enrolled in the OLE study if they fulfill all 3 of the following
             criteria prior to the first dose of study treatment:

               1. Active TB is ruled out by a certified TB specialist or pulmonologist who is
                  familiar with diagnosing and treating TB (as acceptable per local practice);

               2. The subject starts prophylaxis for latent TB infection (LTBI) according to
                  country-specific/Centers for Disease Control and Prevention (CDC) guidelines
                  (treatment with isoniazid for 6 months is not an appropriate prophylactic regime
                  for this study and it should not be used); and

               3. The subject is willing to complete the entire course of recommended LTBI therapy.

          4. Subject has planned surgery during the first 12 weeks of the OLE study

          5. Female subjects who are pregnant or who are planning to become pregnant during the
             study or within 6 months of the last dose of study drug

          6. Female subjects of childbearing potential (unless permanent cessation of menstrual
             periods, determined retrospectively after a woman has experienced 12 months of natural
             amenorrhea as defined by the amenorrhea with underlying status [e.g., correlative age]
             or 6 months of natural amenorrhea with documented serum follicle-stimulating hormone
             levels >40 mIU/mL and estradiol <20 pg/mL) who are not willing to use a highly
             effective method of contraception during the study and for at least 6 months after the
             last administration of study treatment OR Male subjects with partners of childbearing
             potential not willing to use a highly effective method of contraception during the
             study and for at least 3 months after the last administration of study treatment.

             Highly effective contraception is defined as:

               -  Female sterilization surgery: hysterectomy, surgical bilateral oophorectomy (with
                  or without hysterectomy) or tubal ligation at least 6 weeks prior to the first
                  dose of study treatment in the core study

                    -  In the case of oophorectomy alone, only when the reproductive status of the
                       woman has been confirmed by documented follow-up hormone level assessment

               -  Total abstinence if it is the preferred and constant lifestyle of the subject.
                  Thus, periodic abstinence such as ovulation, symptothermal, postovulation,
                  calendar methods, and withdrawal are not acceptable methods of contraception.

               -  Male sterilization surgery: at least 6 months prior to the first dose of study
                  treatment in the core study (with the appropriate postvasectomy documentation of
                  the absence of sperm in the ejaculate). For female subjects, the vasectomized
                  male should be the only partner.

               -  Placement of established intrauterine device (IUD): IUD copper or IUD with
                  progesterone

               -  Barrier method (condom and intravaginal spermicide, cervical caps with
                  spermicide, or diaphragm with spermicide) in combination with the following:
                  established oral, injected, or implanted hormone methods of contraception or
                  contraceptive patch.

          7. Subject is unwilling or unable to follow the procedures outlined in the protocol.

          8. Other medical or psychiatric conditions, or laboratory abnormalities that may increase
             the potential risk associated with study participation and administration of the study
             treatment, or that may affect study results interpretation and, as per Investigator's
             judgement, make the subject ineligible.