An Investigator-initiated Double-blind, Parallel-group Randomised Controlled Trial of GOLimumab and Methotrexate Versus Methotrexate in Very Early PsA Using Clinical and Whole Body MRI Outcomes: the GOLMePsA Study.
An Investigator-initiated Double-blind, Parallel-group Randomised Controlled Trial of GOLimumab and Methotrexate Versus Methotrexate in Very Early PsA Using Clinical and Whole Body MRI Outcomes: the GOLMePsA Study.
An investigator-initiated double-blind, parallel-group randomised controlled trial of Methotrexate versus GOLimumab and Methotrexate in very early PsA using clinical and whole body MRI outcomes.
Phase IIIb. Early Psoriatic Arthritis. Investigator initiated, double-blind, randomized, placebo-controlled, two-armed, parallel-group, single centre trial.
The Primary Objective is to assess whether the combination of golimumab with methotrexate and steroids is superior to standard care (MTX monotherapy plus steroids) in reducing clinical disease activity in patients with early, treatment naïve PsA.
Inclusion Criteria:
Male and female patients aged ≥18 years at the time of signing the Informed Consent Form.
Subjects with a diagnosis of psoriatic arthritis as per the Classification for Psoriatic Arthritis (CASPAR) criteria (Appendix 4) confirmed less than 24 months prior to screening.
Subjects with active PsA defined as the presence of at least 3/68 tender and at least 3/66 swollen joints or 2 swollen and 2 tender joints plus one affected entheseal site (Achilles tendon and/or plantar fascia) at baseline.
Are treatment naïve to DMARDs. Are capable of understanding and signing an informed consent form. Women of childbearing potential or men capable of fathering children must be using adequate birth control measures (eg, abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, surgical sterilization) during the study and for 6 months after receiving the last administration of study agent. Female subjects of childbearing potential must test negative for pregnancy. Female subjects must agree to not donate eggs (ova, oocytes) during the study and for 6 months after last dose of study agent. Male subjects must agree to not donate sperm while in the study and for 6 months after last dose of study agent.
Patients fulfilling the following TB criteria:
7.1. Have no history of latent or active TB prior to screening. An exception is made for subjects with a history of latent TB and documentation of having completed appropriate treatment for latent TB 3 years prior to the first administration of study agent. It is the responsibility of the investigator to verify the adequacy of previous antituberculous treatment and provide appropriate documentation.
7.2. Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination.
7.3. Have had no close contact with a person with active TB or, if there has been such a contact, will be referred to a physician specializing in TB to undergo additional evaluation, and if warranted, receive appropriate treatment as if having latent TB prior to or simultaneously with the first administration of study agent.
7.4. Within 6 weeks prior to the administration of study agent, either have a negative QuantiFERON-TB Gold test result or have a newly identified positive QuantiFERON-TB Gold test result in which active TB has been ruled out and for which appropriate treatment for latent TB has been initiated either prior to or simultaneously with the first administration of study agent.
7.5. In the event of 2 indeterminate QuantiFERON-TB Gold in-tube tests results, the subjects will be treated as if having latent TB prior or simultaneously with the first administration of study agent.
7.6. Have a chest radiograph (posterior-anterior view), read by a qualified radiologist, whose diagnostic assessment is consistent with no evidence of current active TB or old inactive TB, and taken within 12 months of the study.
7.7. Have a screening laboratory test result as follows: 7.7.1. Hb≥8.5 g/dL or ≥5.3 mmol/L 7.7.2. White blood cell (WBC) count ≥3.5x103 cells/uL 7.7.3. Neutrophils ≥1.5 x103 cells/uL 7.7.4. Platelets ≥100x103 cells/uL 7.7.5. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels not exceeding 1.5 times the upper limit of normal (UKN) for the central laboratory conducting the test.
7.7.6. Serum creatinine not exceeding 1.5 mg/dL
Exclusion Criteria:
Patients with significant concurrent medical diseases including uncompensated congestive heart failure, myocardial infarction within 52 weeks from screening, unstable angina pectoris, uncontrolled hypertension (BP>160/95), severe pulmonary disease, or history of human immunodeficiency virus (HIV) infection, immunodeficiency syndromes, central nervous system (CNS) demyelinating events suggestive of multiple sclerosis, renal or gastrointestinal conditions, which in the opinion of the investigator places the patient at an unacceptable risk for participation in the study or would make implementation of the protocol difficult.
Patients with cancer or a history of cancer (other than resected cutaneous basal cell carcinoma, and in situ cervical cancer) within 5 years of screening.
Patients with current crystal or infective arthritis. Patients with chronic infection of the upper respiratory tract (eg. Sinusitis), chest (eg. Bronchiectatic lung disease), urinary tract or skin (eg. Paronychia, chronic ulcers, open wounds) within 4 weeks of screening.
Patients who have a chest radiograph within 3 months prior to the first administration of study agent that shows an abnormality suggestive of a malignancy or current active infection, including TB, histoplasmosis or coccidioidomycosis.
Patients with any ongoing or active infection or any major episode of infection requiring hospitalization or treatment with IV antibiotics within the preceding 30 days of screening and/or orally administered antibiotics in the preceding 15 days of screening.
Patients with abnormal liver function including known liver cirrhosis, fibrosis, or known alcoholic steatohepatitis (NASH) at the time of screening or abnormal blood tests as shown by:
Aminotransferase (AST) / alanine aminotransferase (ALT) > 3x ULN, OR Bilirubin >51umol/L
Patients with known severe hypoproteinaemia at the time of screening, e.g. in nephrotic syndrome or impaired renal function, as shown by:
• Serum Creatinine > 133 mol/L
Patients with known significantly impaired bone marrow function as for example significant anaemia, leukopaenia, neutropaenia or thrombocytopaenia as shown by the following laboratory values at the time of screening:
White blood cells < 3000 x 106/L Platelets < 125 x 109/L Haemoglobin < 9.0 g/dL for males and < 8.5 g/dL for females Patients with a history of latent or active TB prior to screening will not be eligible. For exceptions refer to inclusion criteria.
Subjects must undergo screening for hepatitis B virus (HBV). At a minimum, this includes testing for HBsAg (surface antigen), anti-HBs (surface antibody), and anti-HBc total (core antibody total).
11.1. Subjects who test positive for surface antigen (HBsAg+) are not eligible for this study, regardless of the results of other hepatitis B tests.
11.2. Subjects who test negative for surface antibody (HBsAg-) and test positive for core antibody (anti-HBc+) and surface antibody (anti-HBs+) are eligible for this study.
11.3. Subjects who test positive only for surface antibody (anti-HBs+) are eligible for this study.
11.4. Subjects who test positive only for core antibody (anti-HBc+) must undergo further testing for hepatitis B deoxyribonucleic acid (HBV DNA test). If the HBV DNA test is positive, the subject is not eligible for this study. If the HBV DNA test is negative, the subject is eligible for this study. In the event the DNA test cannot be performed, the subject is not eligible for the study.
Primary or secondary immunodeficiency (history of or currently active) unless related to primary disease under investigation.
Pregnancy, lactation (nursing) or women of child-bearing potential (WCBP) unwilling to use an effective birth control measure (Appendix 1) whilst receiving treatment and after the last dose of protocol treatment as indicated in the relevant SmPC/IB.
Men whose partners are of child-bearing potential but who are unwilling to use an effective birth control measure whilst receiving treatment and after the last dose of protocol treatment as indicated in the relevant SmPC/IB.
Patients who have received any corticosteroids within 4 weeks prior to screening.
Patients with a history of confirmed blood dyscrasia. Patients with a history of mental illness that would interfere with their ability to comply with the study protocol.
Patients with a history of drug and/or alcohol abuse that would interfere with their ability to comply with the study protocol.
Patients with a history of any viral hepatitis within 1 year of screening Patients who have received or are expected to receive any live virus or bacterial vaccinations or treatments that include live organisms (eg. a therapeutic infectious agent such as BCG that is instilled into the bladder for the treatment of cancer) within 3 months prior to the first administration of study agent, during the trial, or within 6 months after the last administration of the study agent.
Patients who demonstrate Hypersensitivity to the active substance, or any of the excipients detailed in the SmPC.