A Multi-centre Long-term Extension Study to Assess the Safety and Efficacy of GSK3196165 in the Treatment of Rheumatoid Arthritis
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 2,916
- 试验地点
- 1
- 主要终点
- Change From Baseline in Hematology Parameter of Platelet Count at Week 24
研究概览
简要总结
RA is a chronic, systemic inflammatory autoimmune disease which requires treatment for a long time period, hence it is important to study the long-term safety and efficacy of the continuous treatment with GSK3196165 over several years. This is a Phase 3, multicenter, parallel group treatment and long-term extension study primarily to assess safety with efficacy assessment as a secondary objective. Adult participants with RA who have completed the treatment phase of a qualifying GSK3196165 clinical studies (Phase 3 studies contRAst 1 (201790: NCT03980483), contRAst 2 (201791: NCT03970837) and contRAst 3 (202018: NCT04134728) and who, in investigator's judgement will benefit from extended treatment with GSK3196165 will be included in this study (contRAst X [209564: NCT04333147]). Participants will continue to receive the same background conventional synthetic disease modifying anti-rheumatic drug(s) [csDMARD(s)] treatment as they received in their qualifying study. Eligible participants will be enrolled to receive weekly GSK3196165 90 milligrams (mg) or 150 mg by subcutaneous (SC) injection. The anticipated study duration is approximately 4 years which will enable participants to receive treatment with GSK3196165 until it is expected to become commercially available. Approximately 3000 participants from the qualifying studies will participate in this long-term extension study
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
This is a parallel group treatment study with two arms that are initially participant and investigator blinded. A participant's treatment allocation will remain blinded at least until their qualifying study has been reported.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with rheumatoid arthritis who are aged >=18 years at the time of signing informed consent, who have completed one of the qualifying GSK3196165 clinical studies and who, in the opinion of the investigator, may benefit from treatment with GSK
- •Body weight >=40 kilograms (kg).
- •Male or female participants are eligible to participate as long as they meet the contraceptive eligibility criteria and agree to abide by the contraceptive requirements.
- •Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
- •For participants on methotrexate (MTX): must be willing to continue treatment with oral folic acid (at least 5 mg/week) or equivalent while receiving MTX (mandatory co-medication for MTX treatment).
排除标准
- •Had study intervention permanently discontinued at any time during a qualifying study except any participant with a new diagnosis of latent Mycobacterium tuberculosis (TB) at the end of study assessment in a qualifying study and currently undertaking or willing to complete at least 4 weeks of anti-TB treatment off study treatment, per world health organization (WHO) or national guidelines prior to re-commencing therapy and complete the remainder of anti-TB treatment while on study.
- •Evidence of latent TB (as documented by a positive QuantiFERON-TB Gold plus test or T-SPOT.TB test, no findings on medical history or clinical examination consistent with active TB, and a normal chest radiograph) except for participants that
- •Are currently undertaking or willing to complete at least 4 weeks of anti-TB therapy off study treatment, as per WHO or national guidelines prior to re- commencing study treatment and agree to complete the remainder of anti-TB treatment while in the study or
- •Had documented evidence of satisfactory anti-TB treatment as per WHO or national guidelines following review by a physician specializing in TB on entry to a qualifying study.
- •Current or previous active TB regardless of treatment.
- •Were temporarily discontinued from study intervention at the time of the final study visit of a qualifying study and, in the opinion of the investigator, participation in the extension study poses an unacceptable risk for the participant's participation.
- •A new cancer or malignancy except for basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix treated and considered cured by the investigator.
- •Have developed any lymphoproliferative disorder during a qualifying study, such as Epstein Barr Virus (EBV) related lymphoproliferative disorder, or signs and symptoms suggestive of current lymphatic disease.
- •Have significant uncontrolled cardiovascular, cerebrovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, or neuropsychiatric disorders, or abnormal laboratory values that developed during a qualifying study that, in the opinion of the investigator, poses an unacceptable risk for the participant's participation.
- •Participants who are expected to be non-compliant with restrictions on medications and vaccinations prior to the study, during the study or during the 8-week safety follow-up of the study.
- •Participants who are currently participating in any interventional clinical study other than a qualifying GSK3196165 clinical study.
- •Abnormal chest radiograph within the last 12 weeks judged by the investigator as clinically-significant.
- •Pregnant or lactating, or women planning to become pregnant or initiating breastfeeding.
- •History of sensitivity to any of the study treatments, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
研究组 & 干预措施
Otilimab 90 mg
Participants who received Otilimab 90mg in a qualifying study and continued on Otilimab 90mg in study 209564 or participants who received either tofacitinib 5mg (study 201790 or 201791) or sarilumab 200mg (study 202018) in a qualifying study and were exposed for the first time to Otilimab 90mg in study 209564. Otilimab 90mg was administered through subcutaneous (SC) injection once weekly.
干预措施: Otilimab (GSK3196165) (Biological)
Otilimab 90 mg
Participants who received Otilimab 90mg in a qualifying study and continued on Otilimab 90mg in study 209564 or participants who received either tofacitinib 5mg (study 201790 or 201791) or sarilumab 200mg (study 202018) in a qualifying study and were exposed for the first time to Otilimab 90mg in study 209564. Otilimab 90mg was administered through subcutaneous (SC) injection once weekly.
干预措施: csDMARD(s) (Drug)
Otilimab 150 mg
Participants who received Otilimab 150mg in a qualifying study and continued on Otilimab 150mg in study 209564 or participants who received either tofacitinib 5mg (study 201790 or 201791) or sarilumab 200mg (study 202018) in a qualifying study and were exposed for the first time to Otilimab 150mg in study 209564. Otilimab 150mg was administered through subcutaneous (SC) injection once weekly.
干预措施: Otilimab (GSK3196165) (Biological)
Otilimab 150 mg
Participants who received Otilimab 150mg in a qualifying study and continued on Otilimab 150mg in study 209564 or participants who received either tofacitinib 5mg (study 201790 or 201791) or sarilumab 200mg (study 202018) in a qualifying study and were exposed for the first time to Otilimab 150mg in study 209564. Otilimab 150mg was administered through subcutaneous (SC) injection once weekly.
干预措施: csDMARD(s) (Drug)
结局指标
主要结局
Change From Baseline in Hematology Parameter of Platelet Count at Week 24
时间窗: Baseline (Day 01) and Week 24
Blood samples were collected for the assessment of change from baseline in hematology parameter platelet count.
Change From Baseline in Hematology Parameter of Platelet Count at Week 96
时间窗: Baseline (Day 01) and Week 96
Blood samples were collected for the assessment of change from baseline in hematology parameter platelet count.
Change From Baseline in Hematology Parameter of Platelet Count at Week 48
时间窗: Baseline (Day 01) and Week 48
Blood samples were collected for the assessment of change from baseline in hematology parameter platelet count.
Change From Baseline in White Blood Cell (WBC) Count With Differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils at Week 24
时间窗: Baseline (Day 01) and Week 24
Blood samples were collected for the assessment of change from baseline in hematology parameters including White Blood Cell (WBC) Count with Differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils.
Change From Baseline in Clinical Chemistry Parameter of Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (AP), Gamma Glutamyl Transferase (GGT), Creatine Kinase (CPK) at Week 48
时间窗: Baseline (Day 01) and Week 48
Blood samples were collected for the assessment of change from baseline in clinical chemistry parameters including AST, ALT, AP, GGT, CPK.
Change From Baseline in Lipid Profile Parameter of Cholesterol, Low-Density Lipoprotein (LDL) Cholesterol, High-Density Lipoprotein-Cholesterol (HDL), Triglycerides at Week 96
时间窗: Baseline (Day 01) and Week 96
Blood samples was collected for the assessment of clinical chemistry parameters including Cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein-cholesterol (HDL), Triglycerides
Change From Baseline in Clinical Chemistry Parameter Total Bilirubin, Direct Bilirubin at Week 24
时间窗: Baseline (Day 01) and Week 24
Blood samples were collected for the assessment of change from baseline in clinical chemistry parameters including total bilirubin, direct bilirubin.
Change From Baseline in Hematology Parameter of Platelet Count at Week 144
时间窗: Baseline (Day 01) and Week 144
Blood samples were collected for the assessment of change from baseline in hematology parameter platelet count.
Change From Baseline in Clinical Chemistry Parameter of Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (AP), Gamma Glutamyl Transferase (GGT), Creatine Kinase (CPK) at Week 144
时间窗: Baseline (Day 01) and Week 144
Blood samples were collected for the assessment of change from baseline in clinical chemistry parameters including AST, ALT, AP, GGT, CPK.
Change From Baseline in Clinical Chemistry Parameter Total Bilirubin, Direct Bilirubin at Week 144
时间窗: Baseline (Day 01) and Week 144
Blood samples were collected for the assessment of change from baseline in clinical chemistry parameters including total bilirubin, direct bilirubin.
Change From Baseline in Hematology Parameter of Hemoglobin at Week 24
时间窗: Baseline (Day 01) and Week 24
Blood samples were collected for the assessment of change from baseline in hematology parameter hemoglobin.
Change From Baseline in Hematology Parameter of Hemoglobin at Week 96
时间窗: Baseline (Day 01) and Week 96
Blood samples were collected for the assessment of change from baseline in hematology parameter hemoglobin.
Change From Baseline in White Blood Cell (WBC) Count With Differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils at Week 48
时间窗: Baseline (Day 01) and Week 48
Blood samples were collected for the assessment of change from baseline in hematology parameters including White Blood Cell (WBC) Count with Differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils.
Change From Baseline in White Blood Cell (WBC) Count With Differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils at Week 144
时间窗: Baseline (Day 01) and Week 144
Blood samples were collected for the assessment of change from baseline in hematology parameters including White Blood Cell (WBC) Count with Differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils.
Change From Baseline in Lipid Profile Parameter of Cholesterol, Low-Density Lipoprotein (LDL) Cholesterol, High-Density Lipoprotein-Cholesterol (HDL), Triglycerides at Week 24
时间窗: Baseline (Day 01) and Week 24
Blood samples was collected for the assessment of clinical chemistry parameters including Cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein-cholesterol (HDL), Triglycerides
Change From Baseline in Lipid Profile Parameter of Cholesterol, Low-Density Lipoprotein (LDL) Cholesterol, High-Density Lipoprotein-Cholesterol (HDL), Triglycerides at Week 144
时间窗: Baseline (Day 01) and Week 144
Blood samples was collected for the assessment of clinical chemistry parameters including Cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein-cholesterol (HDL), Triglycerides
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI)
时间窗: Up to approximately 145 Weeks
An AE is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAEs are defined as any untoward medical occurrence that, at any dose: results in death, cause life threatening events which requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability or incapacity and birth defect or congenital anomaly. Protocol defined AESIs were included.
Change From Baseline in Hematology Parameter of Hemoglobin at Week 48
时间窗: Baseline (Day 01) and Week 48
Blood samples were collected for the assessment of change from baseline in hematology parameter hemoglobin.
Change From Baseline in Hematology Parameter of Hemoglobin at Week 144
时间窗: Baseline (Day 01) and Week 144
Blood samples were collected for the assessment of change from baseline in hematology parameter hemoglobin.
Change From Baseline in White Blood Cell (WBC) Count With Differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils at Week 96
时间窗: Baseline (Day 01) and Week 96
Blood samples were collected for the assessment of change from baseline in hematology parameters including White Blood Cell (WBC) Count with Differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils.
Change From Baseline in Clinical Chemistry Parameter of Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (AP), Gamma Glutamyl Transferase (GGT), Creatine Kinase (CPK) at Week 24
时间窗: Baseline (Day 01) and Week 24
Blood samples were collected for the assessment of change from baseline in clinical chemistry parameters including AST, ALT, AP, GGT, CPK.
Change From Baseline in Clinical Chemistry Parameter of Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (AP), Gamma Glutamyl Transferase (GGT), Creatine Kinase (CPK) at Week 96
时间窗: Baseline (Day 01) and Week 96
Blood samples were collected for the assessment of change from baseline in clinical chemistry parameters including AST, ALT, AP, GGT, CPK.
Change From Baseline in Lipid Profile Parameter of Cholesterol, Low-Density Lipoprotein (LDL) Cholesterol, High-Density Lipoprotein-Cholesterol (HDL), Triglycerides at Week 48
时间窗: Baseline (Day 01) and Week 48
Blood samples was collected for the assessment of clinical chemistry parameters including Cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein-cholesterol (HDL), Triglycerides
Change From Baseline in Clinical Chemistry Parameter Total Bilirubin, Direct Bilirubin at Week 48
时间窗: Baseline (Day 01) and Week 48
Blood samples were collected for the assessment of change from baseline in clinical chemistry parameters including total bilirubin, direct bilirubin.
Number of Participants With National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE)>=Grade 3 Hematological/Clinical Chemistry Abnormalities
时间窗: Up to approximately 145 Weeks
Number of participants with NCI-CTCAE \>=Grade 3 hematological/clinical chemistry abnormalities were summarized. Hematological and Clinical chemistry parameters were summarized according to the NCI-CTCAE, version 5.0: Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening or disabling. Higher grade indicates more severity. Data is presented for only those parameters for which participants had worst case \>=Grade 3 shifts from Baseline.
Change From Baseline in Clinical Chemistry Parameter Total Bilirubin, Direct Bilirubin at Week 96
时间窗: Baseline (Day 01) and Week 96
Blood samples were collected for the assessment of change from baseline in clinical chemistry parameters including total bilirubin, direct bilirubin.
次要结局
- Absolute Values for Disease Activity Score Using 28 Joint Count and C-Reactive Protein (DAS28-CRP)(Week 24, 48, 96 and 144)
- Percentage of Participants Achieving Clinical Disease Activity Index (CDAI) Total Score Lesser Than or Equal to (<=)10 (CDAI) Low Disease Activity (LDA) at Week 24, 48, 96 and 144(Week 24, 48, 96 and 144)
- Percentage of Participants Achieving Disease Activity Score Using 28 Joint Count and Erythrocyte Sedimentation Rate (ESR) <2.6 (DAS28-ESR Remission) at Week 24, 48, 96 and 132(Week 24, 48, 96 and 132)
- Percentage of Participants Achieving Disease Activity Score Using 28 Joint Count and C-Reactive Protein (DAS28-CRP) <2.6 at Week 24, 48, 96 and 144(Week 24, 48, 96 and 144)
- Percentage of Participants Achieving American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) Remission at Week 24, 48, 96 and 144(Week 24, 48, 96 and 144)
- Absolute Values for Health Assessment Questionnaire Disability Index (HAQ-DI)(Week 24, 48, 96 and 144)
- Absolute Values SF-36 Physical Component Scores (PCS)(Week 24, 48, 96 and 144)
- Percentage of Participants Achieving Clinical Disease Activity Index (CDAI) Total Score <=2.8 (CDAI Remission) at Week 24, 48, 96 and 144(Week 24, 48, 96 and 144)
- Absolute Values for Clinical Disease Activity Index (CDAI) Total Score(Week 24, 48, 96 and 144)
- Absolute Values SF-36 Domain Scores(Week 24, 48, 96 and 144)
- Absolute Values Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue(Week 24, 48, 96 and 144)
- Absolute Values for Disease Activity Score Using 28 Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR)(Week 24, 48, 96 and 132)
- Absolute Values for Arthritis Pain Visual Analogue Scale (VAS)(Week 24, 48, 96 and 144)
- Absolute Values of Van Der Heijde Modified Total Sharp Scores (mTSS)(Week 24 and 48)
- Absolute Values Short Form (SF)-36 Mental Component Scores (MCS)(Week 24, 48, 96 and 144)
- Number of Participants With Anti-GSK3196165 Antibodies(Week 120)