Efficacy of Golimumab in Combination With Methotrexate (MTX) Versus MTX Monotherapy, in Improving Dactylitis, in MTX naïve Psoriatic Arthritis Patients

NCT ID: NCT02065713

Last Updated: 2020-11-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-08-31
• Study Completion Date: 2017-06-30

Brief Summary

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.

Conditions

Psoriatic Arthritis

Keywords

Psoriatic arthritis, dactylitis, enthesitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: EXPERIMENTAL

Golimumab

Intervention Type: DRUG

Prefilled syringe with golimumab 50mg (Simponi®) administrated subcutaneously, once monthly, for 24 weeks.

Methotrexate

Intervention Type: DRUG

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

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.

Group Type: ACTIVE_COMPARATOR

Methotrexate

Intervention Type: DRUG

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

Placebo

Intervention Type: DRUG

The prefilled syringe with placebo will be administrated subcutaneously, once monthly, for 24 weeks.

Interventions

Golimumab

Prefilled syringe with golimumab 50mg (Simponi®) administrated subcutaneously, once monthly, for 24 weeks.

Intervention Type: 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

Intervention Type: DRUG

Placebo

The prefilled syringe with placebo will be administrated subcutaneously, once monthly, for 24 weeks.

Intervention Type: DRUG

Eligibility 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

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Instituto de Medicina Molecular João Lobo Antunes

OTHER

Sponsor Role: lead

Responsible Party

Elsa Vieira de Sousa

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Elsa Vieira de Sousa, MD

Role: PRINCIPAL_INVESTIGATOR

Instituto de Medicina Molecular João Lobo Antunes

Locations

Centro Académico de Medicina de Lisboa

Lisbon, , Portugal

Countries

Portugal

References

Vieira-Sousa E, Alves P, Rodrigues AM, Teixeira F, Tavares-Costa J, Bernardo A, Pimenta S, Pimentel-Santos FM, Gomes JL, Aguiar R, Pinto P, Videira T, Catita C, Santos H, Borges J, Sequeira G, Ribeiro C, Teixeira L, Avila-Ribeiro P, Martins FM, Canhao H, McInnes IB, Ribeiro RM, Fonseca JE. GO-DACT: a phase 3b randomised, double-blind, placebo-controlled trial of GOlimumab plus methotrexate (MTX) versus placebo plus MTX in improving DACTylitis in MTX-naive patients with psoriatic arthritis. Ann Rheum Dis. 2020 Apr;79(4):490-498. doi: 10.1136/annrheumdis-2019-216500.

Reference Type: DERIVED

PMID: 32193187 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IMM-50307

Identifier Type: -

Identifier Source: org_study_id