Initial Treatment With Golimumab in Early PsA

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor:
Information provided by (Responsible Party):
D.L.P. (Dominique) Baeten, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier:
NCT01871649
First received: January 7, 2013
Last updated: February 10, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Psoriatic Arthritis
Drug: golimumab
Drug: methotrexate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled Trial of Golimumab+Methotrexate Versus Methotrexate Alone in Methotrexate-naïve Patients With Psoriatic Arthritis

Resource links provided by NLM:


Further study details as provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):

Primary Outcome Measures:
  • Percentage of patients achieving DAS remission response criteria [ Time Frame: week 22 ] [ Designated as safety issue: No ]

    1. To demonstrate that golimumab + MTX is superior to MTX alone in achieving DAS remission in MTX naïve PsA patients at week 22

    DAS = Disease activity score, remission is defined as a DAS < 1.6


  • Number of Participants with Adverse Events [ Time Frame: week 22 ] [ Designated as safety issue: Yes ]

    Number of patients with(severe) adverse events (and type) during the study period.

    Safety will be monitored during the study period by laboratory tests and physical examination.



Secondary Outcome Measures:
  • Number of patients fulfilling Minimal Disease activity criteria and other outcome measurements [ Time Frame: week 22 ] [ Designated as safety issue: No ]
    To demonstrate that golimumab + MTX is superior to MTX alone as assessed by DAS, ACR and PsARC responses, as well as by achievement of low disease activity (LDA, as defined by DAS<2.4) and minimal disease activity (MDA, as defined by Coates et al, Ann Rheum Dis 2010). Also the Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) score and Psoriasis Area Severity Index (PASI) score will be determined in MTX naïve PsA patients at week 22.


Other Outcome Measures:
  • Efficacy after withdrawing anti-TNF [ Time Frame: week 50 ] [ Designated as safety issue: No ]
    To demonstrate that initial treatment of MTX naïve patients with golimumab + MTX is superior to MTX alone to maintain DAS (disease activity score) remission, LDA (Low Disease Activity) and MDA over time (up to week 50) after withdrawing golimumab.


Estimated Enrollment: 60
Study Start Date: September 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: methotrexate
methotrexate is the active comparator, it will be compared to golimumab + methotrexate
Drug: methotrexate
Methotrexate will be started at a dosage of 15 mg/week orally and, if well tolerated, increased to 20mg/week at week 4 and 25mg/week at week 8 of the trial. If well tolerated, the maximum dose of 25 mg/week will be sustained until end of study (week 50). Folic acid 5 mg/week will be administered orally one day after the MTX intake.
Other Name: N.A.
Experimental: golimumab and methotrexate
The combination of golimumab en methotrexate will be compared to methotrexate alone.
Drug: golimumab
golimumab 50mg subcutaneous injections (in combination with methotrexate), once a month, for a period of 22 weeks
Other Name: simponi

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01871649

Contacts
Contact: Dominique LP Baeten, Prof. dr. MD +31 20 5667765 d.l.baeten@amc.uva.nl
Contact: Leonieke JJ Van Mens, MD +31 20 5667765 l.j.vanmens@amc.uva.nl

Locations
Netherlands
Academic Medical Center/University of Amsterdam Recruiting
Amsterdam, Noord Holland, Netherlands, 1105 AZ
Contact: Dominique LP Baeten, Prof. dr. MD    +31 20 5667765    d.l.baeten@amc.uva.nl   
Contact: Leonieke JJ Van Mens, MD    +31 20 5667765    l.j.vanmens@amc.uva.nl   
Principal Investigator: Dominique LP Baeten, Prof dr MD         
Reade Recruiting
Amsterdam, Noord Holland, Netherlands, 1056 AB
Contact: Arno WR Van Kuijk, MD, PhD    +31 20 5896589    a.w.vankuijk@amc.uva.nl   
Contact: Leonieke Van Mens, MD    +31 205896222    psastudies@reade.nl   
Principal Investigator: Arno WR Van Kuijk, MD PhD         
Sponsors and Collaborators
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Investigators
Principal Investigator: Dominique LP Baeten, Prof. dr. MD Academic Medical Center, University of Amsterdam
  More Information

No publications provided

Responsible Party: D.L.P. (Dominique) Baeten, prof. dr., Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT01871649     History of Changes
Other Study ID Numbers: AMC_ 42670_PsA_Golimumab
Study First Received: January 7, 2013
Last Updated: February 10, 2014
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):
psoriatic arthritis
golimumab
methotrexate
minimal disease activity
safety
withdrawal

Additional relevant MeSH terms:
Arthritis, Psoriatic
Arthritis
Joint Diseases
Musculoskeletal Diseases
Spondylarthropathies
Spondylarthritis
Spondylitis
Spinal Diseases
Bone Diseases
Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on July 26, 2014