Efficacy of Golimumab in Combination With Methotrexate (Mtx) Versus Mtx Monotherapy, in Improving Dactylitis, in Mtx naïve Psoriatic Arthritis Patients (GO-DACT)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified February 2014 by Instituto de Medicina Molecular
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Elsa Vieira de Sousa, Instituto de Medicina Molecular
ClinicalTrials.gov Identifier:
NCT02065713
First received: February 17, 2014
Last updated: February 18, 2014
Last verified: February 2014
  Purpose

Dactylitis is a poor prognostic factor in psoriatic arthritis (PsA) patients. The efficacy of synthetic or biologic disease modifying anti-rheumatic drugs (DMARDs) on dactylitis has not been previously studied in randomized controlled trials as a primary endpoint.

In this investigator initiated clinical trial the investigators aim to test the hypothesis that the combination therapy of golimumab and methotrexate (MTX) will result in a significant improvement of dactylitis in comparison with MTX monotherapy, in MTX naïve psoriatic arthritis patients, at week 24. Similarly the efficacy on enthesitis, peripheral and axial involvement, skin and nail psoriasis, inflammation and damage of the feet and hands assessed by magnetic resonance imaging (MRI), composite indexes of disease activity, remission, function and quality of life will be determined.

This is a national multicentre, interventional, double-blinded, placebo-controlled, parallel design trial. 136 patients with active dactylitis, refractory to at least two systemic non-steroidal anti-inflammatory drugs (NSAIDs), at optimal dosage, for 3 months will be included and centrally randomized to golimumab in combination with MTX versus MTX monotherapy, in a 1:1 ratio. The study duration will be 24 weeks.

The investigators expect the results from this trial will contribute to a better definition of the treatment algorithm of PsA patients with dactylitis.


Condition Intervention Phase
Psoriatic Arthritis
Drug: Golimumab
Drug: Methotrexate
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A MULTICENTRE, RANDOMIZED, DOUBLE-BLIND, PARALLEL-GROUP STUDY TO COMPARE THE EFFICACY OF GOLIMUMAB IN COMBINATION WITH METHOTREXATE (MTX) VERSUS MTX MONOTHERAPY, IN IMPROVING DACTYLITIS AND ENTHESITIS, IN MTX NAÏVE PSORIATIC ARTHRITIS PATIENTS

Resource links provided by NLM:


Further study details as provided by Instituto de Medicina Molecular:

Primary Outcome Measures:
  • Dactylitis Severity Score (DSS) [ Time Frame: week 24 ] [ Designated as safety issue: No ]
    Changes from baseline of the Dactylitis Severity Score (DSS) at 24 weeks.


Estimated Enrollment: 136
Study Start Date: March 2014
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Golimumab in combination with methotrexate

Golimumab 50mg, subcutaneous, once monthly, for 24 weeks, in combination with MTX.

MTX started at 15mg/weekly at baseline, increased to 20mg/weekly at week 4 and to 25mg/weekly at week 8, maintaining the dose of 25mg/weekly throughout the trial period of 24 weeks, except in case of intolerance or toxicity

Drug: Golimumab
Prefilled syringe with golimumab 50mg (Simponi®) administrated subcutaneously, once monthly, for 24 weeks.
Drug: Methotrexate
MTX started at 15mg/weekly at baseline, increased to 20mg/weekly at week 4 and to 25mg/weekly at week 8, maintaining the dose of 25mg/weekly throughout the trial period of 24 weeks, except in case of intolerance or toxicity
Active Comparator: Placebo in combination with methotrexate
MTX started at 15mg/weekly at baseline, increased to 20mg/weekly at week 4 and to 25mg/weekly at week 8, maintaining the dose of 25mg/weekly throughout the trial period of 24 weeks, except in case of intolerance or toxicity.
Drug: Methotrexate
MTX started at 15mg/weekly at baseline, increased to 20mg/weekly at week 4 and to 25mg/weekly at week 8, maintaining the dose of 25mg/weekly throughout the trial period of 24 weeks, except in case of intolerance or toxicity
Drug: Placebo
The prefilled syringe with placebo will be administrated subcutaneously, once monthly, for 24 weeks.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Each subject must be/have…..

  • Able and willing to give written informed consent and comply with the requirements of the study protocol.
  • Age ≥ 18 years old, at baseline. A subject may be of both gender and any race/ethnicity.
  • PsA diagnosis according to Classification of Psoriatic Arthritis (CASPAR) criteria, established at least 3 months prior to screening.
  • Active psoriatic arthritis, at the time of entry into the study, defined by:

    ≥1 tender dactylitis, refractory to at least two systemic NSAIDs, at optimal dosage, for 3 months and at least one other site of active inflammation (peripheral joints, enthesis, spine, skin or nails).

  • Naïve to MTX therapy.
  • Patients can have been previously treated with synthetic DMARDs (except MTX) or corticosteroids but must have withdrawn according to the following schedules:

    • All synthetic DMARDs and oral corticosteroids withdrawn at least two weeks prior to screening or 5 half lives according, to what is longer, except for leflunomide.
    • leflunomide ≥ 12 weeks or ≥ 2 weeks after standard cholestyramine or activated charcoal washout.
    • Up to a maximum of two local corticosteroids injection are allowed, administrated, at least four weeks prior to screening (indication for local corticoids injection is dependent on expert opinion decision).
    • NSAIDs (up to the maximum recommend dose) if the dose has been stable for at least 4 weeks prior to baseline and the patient is expected to remain on the baseline dose for the 6 months of the study.
  • Female subjects or male subjects and his female sexual partner of childbearing potential must agree to use a medically accepted method of contraception prior to enrollment, while receiving protocol-specified medication and for 6 months after stopping the medication.

    • Medically accepted methods of contraception include condoms (male or female) with a spermicidal agent, diaphragm or cervical cap with spermicide, medically prescribed intrauterine device (IUD), inert or copper containing IUD, hormone-releasing IUD, systemic hormonal contraceptive, and surgical sterilization (eg, hysterectomy or tubal ligation). Other methods may be used as required by local legislation.
    • Postmenopausal women are not required to use contraception (postmenopausal is defined as at least 12 consecutive months without a spontaneous menses).

Exclusion Criteria:

A subject meeting any of the exclusion criteria listed below must be excluded from participating in the trial.

The subject has ….

  • Known or suspected allergy to trial product or related products.
  • Body weight > 100 Kg.
  • Current chronic inflammatory autoimmune disease other than PsA that might confound the evaluations of safety and toxicity such as, but not limited to, ankylosing spondylitis, rheumatoid arthritis, tophaceous gout, reactive arthritis, pseudogout, arthropathy of inflammatory bowel disease, systemic erythematosus lupus, mixed connective tissue disease, scleroderma or variants, and polymyositis
  • Active current infection or history of recurrent or chronic bacterial, viral, fungal, mycobacterial or other infections, including but not limited to tuberculosis and atypical mycobacterial disease, hepatitis B and C, HIV and herpes zoster.
  • History of severe systemic bacterial, viral or fungal infections within the past 12 months prior to screening.
  • Past or current malignancy with the exception of:

    • Adequately treated and cured basal cell carcinoma of the skin occurring more than 12 months prior to screening.
    • Other cancer with a complete response duration of > 5 years or any period of time longer than that, respectively for those malignancies which are considered as resolved after passing this duration of response.
  • Any clinically significant medical condition or situation, other than the condition being studied that, in the opinion of the investigator, would interfere with the trial evaluations or patients safety and optimal participation in the trial such as, but not limited to:

    • Moderate to severe heart failure (New York Heart Association class III/IV)
    • Pre-existing central nervous system demyelinating disorders
    • Increased liver enzymes: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 times the upper limit of normal (ULN).
  • Female subject must not be breast-feeding.
  • Female subject must not be pregnant or intending to become pregnant.
  • Any contra-indications to perform MRI:

    • Patients who have a metal device affected by MRI
    • Allergy or other contraindications to an i.v. injection of gadolinium-diethylenetriamine pentaacetic acid
    • Claustrophobia sufficient to interfere with the patient undergoing the MRI scan.
  • Previous treatment with tumor necrosis factor (TNF) blocking therapy or other biologic agents.
  • Previous MTX therapy.
  • Latent tuberculosis, in the absence of at least one month of isoniazid therapy, according to local guidelines.
  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: NCT02065713

Contacts
Contact: Elsa Vieira de Sousa, MD (+351) 966143235 elsa-sousa@hotmail.com
Contact: Ana Lopes (+351) 2179999544 anafilop@gmail.com

Locations
Portugal
Centro Académico de Medicina de Lisboa Not yet recruiting
Lisbon, Portugal
Contact: Elsa Vieira de Sousa, MD    (+351) 966143235    elsa-sousa@hotmail.com   
Principal Investigator: Elsa Vieira de Sousa, MD         
Sponsors and Collaborators
Instituto de Medicina Molecular
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Elsa Vieira de Sousa, MD Instituto de Medicina Molecular
  More Information

No publications provided

Responsible Party: Elsa Vieira de Sousa, MD, Instituto de Medicina Molecular
ClinicalTrials.gov Identifier: NCT02065713     History of Changes
Other Study ID Numbers: IMM-50307
Study First Received: February 17, 2014
Last Updated: February 18, 2014
Health Authority: Portugal: Ethics Committee for Clinical Research
Portugal: INFARMED, National Authority of Medicines and Health Products, IP

Keywords provided by Instituto de Medicina Molecular:
Psoriatic arthritis, dactylitis, enthesitis

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 August 28, 2014