Last updated: 06/30/2025 12:00:11
Long-term safety and efficacy of GSK3196165 (Otilimab) in the treatment of rheumatoid arthritis (RA)contRAst X
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Other
Other
Trial overview
Official title: A multi-centre long-term extension study to assess the safety and efficacy of GSK3196165 in the treatment of rheumatoid arthritis
Trial description: 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
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Number of participants with adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESI)
Timeframe: Up to approximately 145 Weeks
Change from Baseline in Hematology Parameter of Platelet Count at Week 24
Timeframe: Baseline (Day 01) and Week 24
Change from Baseline in Hematology Parameter of Platelet Count at Week 48
Timeframe: Baseline (Day 01) and Week 48
Change from Baseline in Hematology Parameter of Platelet Count at Week 96
Timeframe: Baseline (Day 01) and Week 96
Change from Baseline in Hematology Parameter of Platelet Count at Week 144
Timeframe: Baseline (Day 01) and Week 144
Change from Baseline in Hematology Parameter of Hemoglobin at Week 24
Timeframe: Baseline (Day 01) and Week 24
Change from Baseline in Hematology Parameter of Hemoglobin at Week 48
Timeframe: Baseline (Day 01) and Week 48
Change from Baseline in Hematology Parameter of Hemoglobin at Week 96
Timeframe: Baseline (Day 01) and Week 96
Change from Baseline in Hematology Parameter of Hemoglobin at Week 144
Timeframe: Baseline (Day 01) and Week 144
Change from Baseline in White Blood Cell (WBC) Count with Differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils at Week 24
Timeframe: Baseline (Day 01) and Week 24
Change from Baseline in White Blood Cell (WBC) Count with Differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils at Week 48
Timeframe: Baseline (Day 01) and Week 48
Change from Baseline in White Blood Cell (WBC) Count with Differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils at Week 96
Timeframe: Baseline (Day 01) and Week 96
Change from Baseline in White Blood Cell (WBC) Count with Differential i.e. Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils at Week 144
Timeframe: Baseline (Day 01) and Week 144
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
Timeframe: Baseline (Day 01) and Week 24
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
Timeframe: Baseline (Day 01) and Week 48
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
Timeframe: Baseline (Day 01) and Week 96
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
Timeframe: Baseline (Day 01) and Week 144
Change from Baseline in Lipid Profile Parameter of Cholesterol, Low-Density Lipoprotein (LDL) Cholesterol, High-Density Lipoprotein-Cholesterol (HDL), Triglycerides at Week 24
Timeframe: Baseline (Day 01) and Week 24
Change from Baseline in Lipid Profile Parameter of Cholesterol, Low-Density Lipoprotein (LDL) Cholesterol, High-Density Lipoprotein-Cholesterol (HDL), Triglycerides at Week 48
Timeframe: Baseline (Day 01) and Week 48
Change from Baseline in Lipid Profile Parameter of Cholesterol, Low-Density Lipoprotein (LDL) Cholesterol, High-Density Lipoprotein-Cholesterol (HDL), Triglycerides at Week 96
Timeframe: Baseline (Day 01) and Week 96
Change from Baseline in Lipid Profile Parameter of Cholesterol, Low-Density Lipoprotein (LDL) Cholesterol, High-Density Lipoprotein-Cholesterol (HDL), Triglycerides at Week 144
Timeframe: Baseline (Day 01) and Week 144
Number of participants with National Cancer Institute-Common terminology criteria for adverse events (NCI-CTCAE)>=Grade 3 hematological/clinical chemistry abnormalities
Timeframe: Up to approximately 145 Weeks
Change from Baseline in Clinical Chemistry Parameter Total Bilirubin, Direct Bilirubin at Week 24
Timeframe: Baseline (Day 01) and Week 24
Change from Baseline in Clinical Chemistry Parameter Total Bilirubin, Direct Bilirubin at Week 48
Timeframe: Baseline (Day 01) and Week 48
Change from Baseline in Clinical Chemistry Parameter Total Bilirubin, Direct Bilirubin at Week 96
Timeframe: Baseline (Day 01) and Week 96
Change from Baseline in Clinical Chemistry Parameter Total Bilirubin, Direct Bilirubin at Week 144
Timeframe: Baseline (Day 01) and Week 144
Secondary outcomes:
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
Timeframe: 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
Timeframe: Week 24, 48, 96 and 144
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
Timeframe: 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
Timeframe: Week 24, 48, 96 and 132
Percentage of participants achieving American College of Rheumatology (ACR)/ European league against rheumatism (EULAR) remission at Week 24, 48, 96 and 144
Timeframe: Week 24, 48, 96 and 144
Absolute Values for Clinical Disease Activity Index (CDAI) total score
Timeframe: Week 24, 48, 96 and 144
Absolute Values for Disease Activity Score using 28 joint count and C-Reactive Protein (DAS28-CRP)
Timeframe: Week 24, 48, 96 and 144
Absolute Values for Disease Activity Score using 28 joint count and Erythrocyte Sedimentation Rate (DAS28-ESR)
Timeframe: Week 24, 48, 96 and 132
Absolute values of Van der Heijde modified total sharp scores (mTSS)
Timeframe: Week 24 and 48
Absolute values for Health Assessment Questionnaire Disability Index (HAQ-DI)
Timeframe: Week 24, 48, 96 and 144
Absolute values for Arthritis pain Visual Analogue Scale (VAS)
Timeframe: Week 24, 48, 96 and 144
Absolute values Short form (SF)-36 Mental Component Scores (MCS)
Timeframe: Week 24, 48, 96 and 144
Absolute values SF-36 domain scores
Timeframe: Week 24, 48, 96 and 144
Absolute values SF-36 Physical Component Scores (PCS)
Timeframe: Week 24, 48, 96 and 144
Absolute values Functional assessment of chronic illness therapy (FACIT)-Fatigue
Timeframe: Week 24, 48, 96 and 144
Number of participants with anti-GSK3196165 antibodies
Timeframe: Week 120
Interventions:
Enrollment:
2916
Primary completion date:
2023-24-02
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Atsumi T, Bracher M, Brooks D, Curtis P, Fleischmann R, Gupta A, et al. . Long-term safety and efficacy of anti-GM-CSF otilimab in patients with rheumatoid arthritis: Long-term extension of three Phase 3 randomised trials (contRAst X). BMJ Open. 2025;15(3) doi:10.1136/bmjopen-2024-088869 https://bmjopen.bmj.com/content/15/3/e088869
Weinblatt ME, Taylor PC, McInnes IB, et alLong-term safety and efficacy of anti-GM-CSF otilimab in patients with rheumatoid arthritis: long-term extension of three phase 3 randomised trials (contRAst X)BMJ Open 2025;15:e088869. doi: 10.1136/bmjopen-2024-088869
PMID: 40044198
DOI: 10.1136/bmjopen-2024-088869
Medical condition
Arthritis, Rheumatoid
Product
Otilimab
Collaborators
IQVIA
Study date(s)
May 2020 to February 2023
Type
Interventional
Phase
3
Participation criteria
Sex
Female & Male
Age
18 Years - NA
Accepts healthy volunteers
No
- 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 GSK3196165.
- Body weight >=40 kilograms (kg).
- 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
Inclusion and exclusion criteria
Inclusion criteria:
- 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 GSK3196165.
- 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).
Exclusion criteria:
- 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 o 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 o 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.
Trial location(s)
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Study documents
Study report synopsis
Available language(s): English
Protocol
Available language(s): English
Statistical analysis plan
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Other
Actual primary completion date
2023-24-02
Actual study completion date
2023-24-02
Plain language summaries
Summary of results in plain language
Available language(s): English, Afrikaans, Bulgarian, Serbian, Czech, Dutch (Belgium), French (Belgium), French (Canadian), German, Hindi, Hungarian, Japanese, Korean, Latvian, Lithuanian, Malay (Malaysia), Polish, Russian, Russian (Ukraine), Sesotho, Chinese (Simplified), Spanish (Argentina), Spanish (Columbia), Spanish (Mexico), Spanish, Thai, Ukrainian, Zulu
To view plain language summaries on trialsummaries.com click here.
Additional information about the trial
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Additional information
201790 contRAst 1 NCT03980483
Click here201791 contRAst 2 NCT03970837
Click here202018 contRAst 3 NCT04134728
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