Clinical trial NCT01871649: Initial Treatment With Golimumab in Early PsA
Official title: A Randomized, Double-blind, Placebo-controlled Trial of Golimumab+Methotrexate Versus Methotrexate Alone in Methotrexate-naïve Patients With Psoriatic Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Psoriatic Arthritis
Keywords: psoriatic arthritis
golimumab
methotrexate
minimal disease activity
safety
withdrawal
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
First posted: 2013-06-07
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The investigators will perform a 22-week randomized, double-blind, placebo-controlled trial of golimumab + methotrexate (MTX) versus methotrexate alone in methotrexate-naïve patients with Psoriatic Arthritis (PsA). Afterwards, a 28 week open label phase with methotrexate alone is started. Golimumab will be discontinued.

Hypotheses:

First, the investigators hypothesize that initiation of a combination therapy with golimumab + MTX will be safe and superior to MTX alone in MTX-naïve PsA patients, as assessed by the percentage of patients achieving Disease Activity Score (the investigators hypothesize that more patients with the early combination treatment will respond (according to Disease Activity Score (DAS), American college of Rheumatology (ACR), or Psoriatic Arthritis Response Criteria (PsARC) responses) and achieve a state of Low Disease Activity (LDA) or Minimal Disease Activity (MDA) than patients on MTX alone.

Third, the investigators hypothesize that a significant proportion of the patients will continue to benefit from this early aggressive treatment initiation even after stopping golimumab treatment.


Eligibility criteria: Inclusion Criteria:

* Prior to any study procedure, voluntary written informed consent must be obtained, after the nature and purpose of this study were explained
* Patients should be between 18 and 70 years of age at time of consent
* Patients must have a diagnosis of PsA according to the Classification for psoriatic Arthritis (CASPAR) classification criteria (see Appendix 1).
* The patient must have an active disease as defined by 3 swollen and 3 tender joints.
* The use of a stable dose of concomitant nonsteroidal antiinflammatory drug (NSAIDs) and/or corticosteroids is allowed. The dose of corticosteroids should not exceed a prednisone equivalent of 10 mg/day and must be stable for at least 4 weeks prior to baseline. The dose of concomitant NSAIDs and corticosteroids should be kept stable during the whole study period.
* Patients are considered to be in generally good health based upon the result of a medical history, physical examination, laboratory profile, chest X-ray and electrocardiography (ECG).

Exclusion Criteria:

* Patient has a concomitant rheumatic condition other than PsA
* Positivity for rheumatoid factor (RF) or anti-cyclic citrullinated peptide (anti CCP) antibodies (ACPA)
* Current or previous use of methotrexate
* Current use of other Disease Modifying Antirheumatic drug (DMARDs) (sulphasalazine or leflunomide).
* Prior use of other DMARDs (sulphasalazine or leflunomide) within 3 months before baseline.
* Current or previous use of biologicals, including Tumor Necrosis Factor (TNF) blocking therapy
* Patient has active tuberculosis. A purified protein derivative (PPD) skin test and chest X-ray at screening should be negative (in case of latent tuberculosis, a patient may enter the study if prophylaxis with isoniazide is begun prior to administration of study medication). If a patient has an adequately treated tuberculosis in the past, he/she may enter the trial.
* Patient has received an intra-articular injection with corticosteroids within 4 weeks prior to baseline.
* Patient has a malignancy (other than basal cell carcinoma of the skin) in the past 5 years
* Patients has a recent history of (or persistent) infection requiring hospitalization or antibiotic treatment within 4 weeks of baseline Patient has a significant history of cardiac, pulmonary, renal (glomerular filtration rate \<40ml/min), hepatic (liver cirrhosis), hematological, neurological, metabolic or any other disease that may affect his/her participation in this study. This should be decided by the opinion of the investigator.
* All females of childbearing potential must use appropriate contraception, be postmenopausal or surgically sterile. A urine pregnancy-test beta-human chorion gonadotropin (Beta-HCG) will be performed at screening and has to be negative.
* Subject is pregnant or a breastfeeding woman
* Liver disease or liver injury as indicated by abnormal liver function tests such as Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), gammaglutamyl transpeptidase (GGT), alkaline phosphatase, or serum bilirubin. The Investigator should be guided by the following criteria: Any single parameter may not exceed 2 x upper limit of normal (ULN).

A single parameter elevated up to and including 2 x ULN should be rechecked once more if elevation levels are found clinically relevant according to the physician, at least prior to enrolment.

- Patient is, in the opinion of the investigator, unable to comply with the requirements of the study protocol or is unsuitable for the study for any reason.

Primary outcomes:
measure: Percentage of patients achieving DAS remission response criteria
timeFrame: week 22
measure: Number of Participants with Adverse Events
timeFrame: week 22
Secondary outcomes:
measure: Number of patients fulfilling Minimal Disease activity criteria and other outcome measurements
timeFrame: week 22
Other outcomes:
measure: Efficacy after withdrawing anti-TNF
timeFrame: week 50
Locations:
city: Amsterdam
country: Netherlands
facility: Reade
state: Noord Holland
city: Amsterdam
country: Netherlands
facility: Academic Medical Center/University of Amsterdam
state: Noord Holland
Study officials:
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Dominique LP Baeten, Prof. dr. MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: de Jong HMY, van Mens LJJ, Nurmohamed MT, Kok MR, van Kuijk AWR, Baeten DLP, van de Sande MGH. Sustained remission with methotrexate monotherapy after 22-week induction treatment with TNF-alpha inhibitor and methotrexate in early psoriatic arthritis: an open-label extension of a randomized placebo-controlled trial. Arthritis Res Ther. 2019 Sep 14;21(1):208. doi: 10.1186/s13075-019-1998-4.
citation: van Mens LJJ, de Jong HM, Fluri I, Nurmohamed MT, van de Sande MGH, Kok M, van Kuijk AWR, Baeten D. Achieving remission in psoriatic arthritis by early initiation of TNF inhibition: a double-blind, randomised, placebo-controlled trial of golimumab plus methotrexate versus placebo plus methotrexate. Ann Rheum Dis. 2019 May;78(5):610-616. doi: 10.1136/annrheumdis-2018-214746. Epub 2019 Feb 26.