Clinical Trials List
Protocol NumberCL04041024
2017-01-01 - 2020-10-31
Phase III
Recruiting2
Terminated1
Study ended1
ICD-10M06.9
Rheumatoid arthritis, unspecified
ICD-9714.0
Rheumatoid arthritis
A Multicenter, Open-label, Phase III Study of the Efficacy and Safety of Olokizumab in Subjects with Moderately to Severely Active Rheumatoid Arthritis
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Trial Applicant
IQVIA RDS Taiwan Ltd.
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Sponsor
R-Pharm
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 劉峰誠 風濕免疫科
- Tsung-Yun Hou 風濕免疫科
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Ping-Han Tsai Division of Rheumatology
- 陳彥輔 Division of Rheumatology
- TianMing Zhan Division of Rheumatology
- Yao-Fan Fang Division of Rheumatology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- Po-Hao Huang 風濕免疫科
- 洪偉哲 風濕免疫科
The Actual Total Number of Participants Enrolled
0 Study ended
Condition/Disease
Rheumatoid Arthritis
Objectives
The primary objective of this study is 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 completed 24 weeks double-blind treatment in Study CL04041022, CL04041023, or CL04041025 (core studies).
Test Drug
Olokizumab
Active Ingredient
Olokizumab
Dosage Form
sterile solution for SC injection
Dosage
160
Endpoints
Criteria for Evaluation:
The following endpoints will be assessed to evaluate treatment with OKZ 64 mg administered SC q2w or q4w for 106 total weeks for subjects randomized to OKZ in all 3 core studies (CL04041022, CL04041023, and CL04041025), and for 82 total weeks for subjects randomized to placebo in the CL04041022 study and to placebo or adalimumab in the CL04041023 core study. In Study CL04041025, subjects randomized to placebo
will transition to OKZ at Week 16 and complete 8 weeks of double-blind treatment with OKZ; these subjects will complete 90 total weeks of treatment with OKZ.
Safety Endpoints:
The nature, incidence, severity, and outcome of adverse events (AEs), including serious adverse events (SAEs) and AEs of special interest (AESIs)
Follow-up- adjusted incidence and event rates (per 100 subject-years of follow-up) for SAEs and AESIs
Proportions of subjects with clinically significant laboratory abnormalities
Assessment of changes over time in clinical laboratory parameters, vital sign measurements, and
physical examination findings
Time from first exposure to OKZ to the first occurrence of any major adverse cardiac event (MACE)
Incidence and titer of antidrug antibodies (ADAs) to OKZ, incidence of neutralizing antibodies, and the time course of antibodies
Efficacy Endpoints:
Proportion of subjects achieving an American College of Rheumatology 20% (ACR20), American College of Rheumatology 50% (ACR50), and American College of Rheumatology 70% (ACR70) response who remain on randomized open-label treatment and in the study, assessed at all applicable time points
Proportion of subjects with Simplified Disease Activity Index (SDAI) ≤3.3 remission, who remain on randomized open-label treatment and in the study, assessed at all applicable time points
Proportion of subjects with Disease Activity Score 28-joint count (DAS28) low disease activity (based on DAS28 C-reactive protein [CRP] <3.2), who remain on randomized open-label treatment and in the study, assessed at all applicable time points
Change from baseline over time in DAS28 (CRP), assessed at all applicable time points
Change from baseline over time in the measure of physical ability based on Health Assessment Questionnaire-Disability Index (HAQ-DI), assessed at all applicable time points
Proportion of subjects with improvement from baseline in HAQ-DI score ≥0.22, who remain on randomized open-label treatment and in the study, assessed at all applicable time points
Change from baseline over time in the scores for the following patient-reported outcomes (PRO)
measures, assessed at all applicable time points:
- Short Form-36 (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) total scores
- European Quality of Life-5 Dimensions (EQ-5D)
- Work Productivity Survey-Rheumatoid Arthritis (WPS-RA)
- Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-Fatigue)
Change from baseline over time in SDAI and Clinical Disease Activity Index (CDAI), assessed at all applicable time points
Proportion of subjects with moderate to good responses for European League Against Rheumatism (EULAR) based on DAS28 (CRP), who remain on randomized open-label treatment and in the study, assessed at all applicable time points, where a moderate response is defined as either DAS28 (CRP) ≤5.1 with an improvement from baseline in DAS28 (CRP) >0.6 and ≤1.2, or DAS28 (CRP) >3.2 with an improvement from baseline in DAS28 (CRP) >1.2, and a good response is defined as DAS28 (CRP) ≤3.2 with an improvement from baseline in DAS28 (CRP) >1.2
Change from baseline to all time points in the components of the ACR response criteria
Immunogenicity:
Evaluating the impact of ADAs to OKZ on subject safety and efficacy
The following endpoints will be assessed to evaluate treatment with OKZ 64 mg administered SC q2w or q4w for 106 total weeks for subjects randomized to OKZ in all 3 core studies (CL04041022, CL04041023, and CL04041025), and for 82 total weeks for subjects randomized to placebo in the CL04041022 study and to placebo or adalimumab in the CL04041023 core study. In Study CL04041025, subjects randomized to placebo
will transition to OKZ at Week 16 and complete 8 weeks of double-blind treatment with OKZ; these subjects will complete 90 total weeks of treatment with OKZ.
Safety Endpoints:
The nature, incidence, severity, and outcome of adverse events (AEs), including serious adverse events (SAEs) and AEs of special interest (AESIs)
Follow-up- adjusted incidence and event rates (per 100 subject-years of follow-up) for SAEs and AESIs
Proportions of subjects with clinically significant laboratory abnormalities
Assessment of changes over time in clinical laboratory parameters, vital sign measurements, and
physical examination findings
Time from first exposure to OKZ to the first occurrence of any major adverse cardiac event (MACE)
Incidence and titer of antidrug antibodies (ADAs) to OKZ, incidence of neutralizing antibodies, and the time course of antibodies
Efficacy Endpoints:
Proportion of subjects achieving an American College of Rheumatology 20% (ACR20), American College of Rheumatology 50% (ACR50), and American College of Rheumatology 70% (ACR70) response who remain on randomized open-label treatment and in the study, assessed at all applicable time points
Proportion of subjects with Simplified Disease Activity Index (SDAI) ≤3.3 remission, who remain on randomized open-label treatment and in the study, assessed at all applicable time points
Proportion of subjects with Disease Activity Score 28-joint count (DAS28) low disease activity (based on DAS28 C-reactive protein [CRP] <3.2), who remain on randomized open-label treatment and in the study, assessed at all applicable time points
Change from baseline over time in DAS28 (CRP), assessed at all applicable time points
Change from baseline over time in the measure of physical ability based on Health Assessment Questionnaire-Disability Index (HAQ-DI), assessed at all applicable time points
Proportion of subjects with improvement from baseline in HAQ-DI score ≥0.22, who remain on randomized open-label treatment and in the study, assessed at all applicable time points
Change from baseline over time in the scores for the following patient-reported outcomes (PRO)
measures, assessed at all applicable time points:
- Short Form-36 (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) total scores
- European Quality of Life-5 Dimensions (EQ-5D)
- Work Productivity Survey-Rheumatoid Arthritis (WPS-RA)
- Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-Fatigue)
Change from baseline over time in SDAI and Clinical Disease Activity Index (CDAI), assessed at all applicable time points
Proportion of subjects with moderate to good responses for European League Against Rheumatism (EULAR) based on DAS28 (CRP), who remain on randomized open-label treatment and in the study, assessed at all applicable time points, where a moderate response is defined as either DAS28 (CRP) ≤5.1 with an improvement from baseline in DAS28 (CRP) >0.6 and ≤1.2, or DAS28 (CRP) >3.2 with an improvement from baseline in DAS28 (CRP) >1.2, and a good response is defined as DAS28 (CRP) ≤3.2 with an improvement from baseline in DAS28 (CRP) >1.2
Change from baseline to all time points in the components of the ACR response criteria
Immunogenicity:
Evaluating the impact of ADAs to OKZ on subject safety and efficacy
Inclution 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).
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
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).
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
Exclusion Criteria
Subjects who meet any of the following criteria will not be eligible for the study:
1. Subject with any medically important condition in the core study (e.g., clinically
significant laboratory values, frequent AEs or SAEs, infection SAEs, and/or other
concurrent severe and/or uncontrolled medical condition) which would make this subject
unsuitable for inclusion in the OLE study in the Investigator’s judgement.
2. Subject has evidence of active 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:
a. 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);
b. The subject starts prophylaxis for LTBI according to country-specific/Centers for
Disease Control and Prevention (CDC) guidelines (see Appendix 4
[Section 13.4]) (treatment with isoniazid for 6 months is not an appropriate
prophylactic regime for this study and it should not be used); and
c. The subject is willing to complete the entire course of recommended LTBI
therapy (see Appendix 4 [Section 13.4]).
4. Subject has planned surgery during the first 12 weeks of the OLE study
5. Female subjects who are pregnant or lactating, or who are planning to become pregnant
during the study or within 6 months of the last dose of study treatment
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.
1. Subject with any medically important condition in the core study (e.g., clinically
significant laboratory values, frequent AEs or SAEs, infection SAEs, and/or other
concurrent severe and/or uncontrolled medical condition) which would make this subject
unsuitable for inclusion in the OLE study in the Investigator’s judgement.
2. Subject has evidence of active 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:
a. 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);
b. The subject starts prophylaxis for LTBI according to country-specific/Centers for
Disease Control and Prevention (CDC) guidelines (see Appendix 4
[Section 13.4]) (treatment with isoniazid for 6 months is not an appropriate
prophylactic regime for this study and it should not be used); and
c. The subject is willing to complete the entire course of recommended LTBI
therapy (see Appendix 4 [Section 13.4]).
4. Subject has planned surgery during the first 12 weeks of the OLE study
5. Female subjects who are pregnant or lactating, or who are planning to become pregnant
during the study or within 6 months of the last dose of study treatment
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.
The Estimated Number of Participants
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Taiwan
21 participants
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Global
1880 participants
