Long-term Safety and Efficacy of GSK3196165 (Otilimab) in the Treatment of Rheumatoid Arthritis (RA)

Phase 3TerminatedNCT04333147

GlaxoSmithKline2,916 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

2,916

Conditions

Arthritis, Rheumatoid

Interventions

Otilimab (GSK3196165)BIOLOGICAL

GSK3196165 solution in vial/pre-filled syringe (PFS) and auto injector (AI) to be administered SC.

csDMARD(s)DRUG

Stable dose of csDMARD(s) as standard of care (SoC).

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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 * 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.

Locations (375)

GSK Investigational Site

Anniston, Alabama, United States

GSK Investigational Site

Flagstaff, Arizona, United States

GSK Investigational Site

Gilbert, Arizona, United States

GSK Investigational Site

Glendale, Arizona, United States

GSK Investigational Site

Mesa, Arizona, United States

GSK Investigational Site

Outcomes

Primary Outcomes

Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI)

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.

Time frame: Up to approximately 145 Weeks

Change From Baseline in Hematology Parameter of Platelet Count at Week 24

Blood samples were collected for the assessment of change from baseline in hematology parameter platelet count.

Time frame: Baseline (Day 01) and Week 24

Change From Baseline in Hematology Parameter of Platelet Count at Week 48

Blood samples were collected for the assessment of change from baseline in hematology parameter platelet count.

Time frame: Baseline (Day 01) and Week 48

Change From Baseline in Hematology Parameter of Platelet Count at Week 96

Blood samples were collected for the assessment of change from baseline in hematology parameter platelet count.

Time frame: Baseline (Day 01) and Week 96

Change From Baseline in Hematology Parameter of Platelet Count at Week 144

Blood samples were collected for the assessment of change from baseline in hematology parameter platelet count.

Time frame: Baseline (Day 01) and Week 144

Change From Baseline in Hematology Parameter of Hemoglobin at Week 24

Blood samples were collected for the assessment of change from baseline in hematology parameter hemoglobin.

Time frame: Baseline (Day 01) and Week 24

Change From Baseline in Hematology Parameter of Hemoglobin at Week 48

Blood samples were collected for the assessment of change from baseline in hematology parameter hemoglobin.

Time frame: Baseline (Day 01) and Week 48

Change From Baseline in Hematology Parameter of Hemoglobin at Week 96

Blood samples were collected for the assessment of change from baseline in hematology parameter hemoglobin.

Time frame: Baseline (Day 01) and Week 96

Change From Baseline in Hematology Parameter of Hemoglobin at Week 144

Blood samples were collected for the assessment of change from baseline in hematology parameter hemoglobin.

Time frame: 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

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.

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Blood samples were collected for the assessment of change from baseline in clinical chemistry parameters including AST, ALT, AP, GGT, CPK.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Blood samples was collected for the assessment of clinical chemistry parameters including Cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein-cholesterol (HDL), Triglycerides

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

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.

Time frame: Up to approximately 145 Weeks

Change From Baseline in Clinical Chemistry Parameter Total Bilirubin, Direct Bilirubin at Week 24

Blood samples were collected for the assessment of change from baseline in clinical chemistry parameters including total bilirubin, direct bilirubin.

Time frame: Baseline (Day 01) and Week 24

Change From Baseline in Clinical Chemistry Parameter Total Bilirubin, Direct Bilirubin at Week 48

Blood samples were collected for the assessment of change from baseline in clinical chemistry parameters including total bilirubin, direct bilirubin.

Time frame: Baseline (Day 01) and Week 48

Change From Baseline in Clinical Chemistry Parameter Total Bilirubin, Direct Bilirubin at Week 96

Blood samples were collected for the assessment of change from baseline in clinical chemistry parameters including total bilirubin, direct bilirubin.

Time frame: Baseline (Day 01) and Week 96

Change From Baseline in Clinical Chemistry Parameter Total Bilirubin, Direct Bilirubin at Week 144

Blood samples were collected for the assessment of change from baseline in clinical chemistry parameters including total bilirubin, direct bilirubin.

Time frame: 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

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. Low disease activity (LDA) is achieved when CDAI total score \<=10. Percentage values are rounded off.

Time frame: 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

Clinical Disease Activity Index (CDAI) total score is a composite score consisting of the sum of Swollen Joint Count 28 (SJC28), Tender Joint Count 28 (TJC28), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst) and Physician Global Assessment of Arthritis Disease Activity (PhGA) (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity. CDAI remission is achieved when CDAI total score \<=2.8. Percentage values are rounded off.

Time frame: 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

The DAS28-CRP is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), C-reactive protein (CRP) (in mg/L), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). PtGA is transformed to a 0-10 scale before computing the total score. DAS28- CRP scores range from 1.0 to 9.4, where lower scores indicates less disease activity. Low disease activity (LDA) is achieved when DAS28-CRP greater than or equal to (\<=)3.2. A negative change from baseline in DAS28-CRP indicates an improvement. Percentage values are rounded off.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Phoenix, Arizona, United States

GSK Investigational Site

Phoenix, Arizona, United States

GSK Investigational Site

Tucson, Arizona, United States

GSK Investigational Site

Covina, California, United States

GSK Investigational Site

Poway, California, United States

...and 365 more locations

Time frame: 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

The DAS28-ESR is a measure of RA disease activity calculated using TJC28,SJC28, ESR (in mm/hr), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). PtGA is transformed to a 0-10 scale before computing the total score. DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity. Remission is achieved when DAS28-ESR \<2.6. A negative change from baseline in DAS28-ESR indicates an improvement. Percentage values are rounded off.

Time frame: 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

Boolean-based ACR/EULAR remission is achieved if all of the following requirements are met at the same timepoint: Tender Joint Count 68 (TJC68) \<= 1, Swollen Joint Count 66 (SJC66) \<= 1, high sensitivity C-reactive Protein (hsCRP) \<= 1mg/dl and patient's global assessment of disease activity (PtGA) \<= 10. Simple Disease Activity Index based ACR/EULAR remission is achieved if a has SDAI \<= 3.3. The SDAI is the sum of the tender/painful joint count and swollen joint count, employing 28 joints; PtGA and PhGA (on a scale of 0-10); and hsCRP (mg/L). Percentage values are rounded off.

Time frame: Week 24, 48, 96 and 144

Absolute Values for Clinical Disease Activity Index (CDAI) Total Score

CDAI total score is a composite score consisting of the sum of TJC28, TJC28, PtGA (visual analogue scale with values from 0=best to 100=worst) and PhGA (visual analogue scale with values from 0=best to 100=worst). PtGA and PhGA are transformed to a 0-10 scale before computing the CDAI total score. CDAI total score ranges from 0 to 76 with higher values representing higher disease activity.

Time frame: Week 24, 48, 96 and 144

Absolute Values for Disease Activity Score Using 28 Joint Count and C-Reactive Protein (DAS28-CRP)

Time frame: Week 24, 48, 96 and 144

Absolute Values for Disease Activity Score Using 28 Joint Count and Erythrocyte Sedimentation Rate (DAS28-ESR)

The DAS28-ESR is a measure of RA disease activity calculated using Tender Joint Count 28 (TJC28), Swollen Joint Count 28 (SJC28), Erythrocyte sedimentation rate (ESR) (in millimeter \[mm\]/hour\[hr\]), Patient's Global Assessment of Arthritis Disease Activity (PtGA) (visual analogue scale with values from 0=best to 100=worst). PtGA is transformed to a 0-10 scale before computing the total score. DAS28-ESR scores range from 1.0 to 9.4, where lower scores indicate less disease activity.

Time frame: Week 24, 48, 96 and 132

Absolute Values of Van Der Heijde Modified Total Sharp Scores (mTSS)

Van der Heijde mTSS is utilized for scoring radiographs of hands and feet in rheumatoid arthritis. This method includes 16 areas of erosions, and 15 areas for joint space narrowing (JSN) in each hand, and 6 areas for erosions and 6 areas JSN in each foot. The total mTSS score is the sum of erosion (maximum of 280) and JSN (maximum of 168) scores. The score ranges from 0 to 448 for mTSS with higher values representing higher disease activity.

Time frame: Week 24 and 48

Absolute Values for Health Assessment Questionnaire Disability Index (HAQ-DI)

The HAQ-DI includes 20 questions which assesses difficulty in performing activities of daily living. The questionnaire assesses eight domains of physical functioning: Dressing and Grooming, Hygiene, Arising, Reach, Eating, Grip, Walking, Common Daily Activities. The questions assess domain scores ranging from 0 "without any difficulty" to 3 "unable to do." Scores on each domain were summed and averaged to provide an overall score ranging from 0 to 3, where higher score reflected worse status and a lower score indicates better quality of life.

Time frame: Week 24, 48, 96 and 144

Absolute Values for Arthritis Pain Visual Analogue Scale (VAS)

For the Arthritis Pain VAS, participants assess the severity of their current arthritis pain using a continuous visual analogue scale (VAS) with anchors at "0" (no pain) and "100" (most severe pain). A negative change from baseline indicates an improvement.

Time frame: Week 24, 48, 96 and 144

Absolute Values Short Form (SF)-36 Mental Component Scores (MCS)

SF-36 is health-related survey that assesses quality of life covering 8 domains:physical functioning,bodily pain,role limitations due to physical/emotional problems,general health,mental health(MH),social functioning(SF),vitality.Each of 8 domains is scored using average, 0-100; higher score represents better health.MCS was aggregated across the domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health. MCS is primarily derived from 4 domains (SF,vitality,MH,role-emotional) representing overall mental health. Quality Metric software was used for scoring.

Time frame: Week 24, 48, 96 and 144

Absolute Values SF-36 Domain Scores

Short-Form 36 (SF-36) is a health-related survey that assesses quality of life covering 8 domains: physical functioning, bodily pain, role limitations due to physical and emotional problems, general health, mental health, social functioning, vitality. The MCS consists of 4 domains (social functioning, vitality, mental health, and role-emotional domains) and PCS consists of 4 domains (physical functioning, role-physical, bodily pain and general health). The individual question items are first summed for each item under the various sections. Then, those domain scores are weighted to a scale between 0 to 100, where higher score represents better health. Quality Metric software was used for scoring for SF-36.

Time frame: Week 24, 48, 96 and 144

Absolute Values SF-36 Physical Component Scores (PCS)

SF-36 is health-related survey that assesses quality of life covering 8 domains:physical functioning(PF),bodily pain(BP),role limitations due to physical/emotional problems,general health(GH),mental health,social functioning,vitality.Each of 8 domains is scored using average, 0-100; higher score represents better health.PCS was aggregated across the domains and scaled to T-score with mean of 50 and SD of 10; higher score represents better health.PCS is primarily derived from 4 domains(PF,role-physical,BP,GH) representing overall physical health. Quality Metric software was used for scoring.

Time frame: Week 24, 48, 96 and 144

Absolute Values Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue

The Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue is a validated patient-reported measure of 13 statements regarding the feeling of fatigue. The total score ranges from 0 to 52 with higher values representing a lower fatigue and a better quality of life.

Time frame: Week 24, 48, 96 and 144

Number of Participants With Anti-GSK3196165 Antibodies

Serum samples were collected for the determination of anti- GSK3196165 antibodies (ADA) using a validated electrochemiluminescence (ECL) immunoassay. The assay involved screening, confirmation and titration steps. If serum samples tested positive in the screening assay, they were considered 'potentially positive' and were further analyzed for the specificity using the confirmation assay. Samples that confirmed positive in the confirmation assay were reported as 'positive'. Confirmed positive ADA samples were further characterized in the titration assay to quasi-quantitate the amount of ADA in the sample. Additionally, confirmed positive ADA samples were also tested in a validated neutralizing antibody assay to determine the potential neutralizing activity of the ADA

Time frame: Week 120