Overview
Exploration of TNF-alpha Blockade With Golimumab in the Induction of Clinical Remission in Patients With Early Peripheral Spondyloarthritis (SpA) According to ASAS-criteria
Status:
Completed
Completed
Trial end date:
2019-03-18
2019-03-18
Target enrollment:
0
0
Participant gender:
All
All
Summary
In this Investigator Initiated study, the investigators want to explore the potential of an induction therapy with Tumor Necrosis Factor (TNF)-blocking agents in a very early disease stage (less than 3 months of symptom duration) of patients with predominant peripheral spondyloarthritis (SpA), classified according to the new Assessment of SpondyloArthritis (ASAS)-criteria. The hypothesis would be that treatment with a TNF-blocker at this early ("immature") stage of the disease would result in a significant higher number of patients in clinical remission compared to placebo, and that - comparable to the early Rheumatoid Arthritis (RA) patients in the BeSt-study - long-term treatment would not be necessary to maintain this remission in a number of patients. In this placebo-controlled, double blind, randomized study (with open-label phase, starting at week 24) sixty patients fulfilling the Assessment of SpondyloArthritis (ASAS) criteria of peripheral spondylarthritis will be enrolled. Patients will be randomized in a 2:1 ratio (2 golimumab :1 placebo). During the placebo-controlled phase, 50mg golimumab, or placebo will be administrated subcutaneously (SC) every 4 weeks through week 20. Subjects will be treated with open-label Golimumab 50 mg SC injections at weeks 24, 28, 32, 36, 40, 44, and 48. If patients are in 'clinical remission' (clinical remission is defined by the absence of arthritis, enthesitis and dactylitis clinically at two major consecutive visits. Visits are planned at week 12, week 24, week 36 and week 48) then the treatment will be stopped. In case of clinical relapse, patients will be treated with open-label golimumab 50 mg SC. Patients in sustained clinical remission will be observed to assess the possibility of maintaining drug-free remission. The study duration will be 48 weeks.Phase:
Phase 3Accepts Healthy Volunteers?
NoDetails
Lead Sponsor:
University Hospital, GhentCollaborator:
Janssen Biologics B.V.Treatments:
Antibodies, Monoclonal
Golimumab
Criteria
Inclusion Criteria:A subject will be eligible for study participation if all of the following criteria are
met:
- Subject is ≥ 18 years of age
- Subjects must meet the new Assessment of SpondyloArthritis (ASAS) criteria for
peripheral spondyloarthritis:
o Subjects must have current arthritis (asymmetric or predominantly in the lower
limbs) or current enthesitis (except for enthesitis only along the spine, sacroiliac
joints and/or chest wall) or current dactylitis PLUS:
- At least 1 of the following Peripheral Spondyloarthritis (SpA) features:
- Anterior uveitis confirmed by an ophthalmologist(past or present)
- Crohn's disease or ulcerative colitis diagnosed by a gastroenterologist (past or
present)
- Evidence of preceding infection (acute diarrhea or non-gonococcal urethritis or
cervicitis 1month before arthritis)
- Psoriasis diagnosed by a dermatologist (past or present)
- Human Leukocyte Antigen (HLA) B27 positivity
- Sacroiliitis by imaging defined as bilateral grade 2-4 or unilateral grade 3-4
sacroiliitis on plain radiographs, according to the modified New York criteria or
active sacroiliitis on Magnetic Resonance Imaging (MRI) according to the ASAS
consensus definition (ref of addendum)
- Subjects must have had onset of peripheral SpA symptoms ≤ 3 months prior to the
screening visit
- Subjects must have active disease at screening and baseline, defined by Patient Global
Assessment of Disease Activity Visual Analog Scale (VAS) ≥ 40mm and Patient Global
Assessment of Pain VAS ≥ 40mm at screening and baseline visits.
- In subjects with concurrent axial SpA symptoms, the peripheral SpA symptoms must be
the predominant symptoms at study entry based on the Investigator's clinical judgment.
- Subject has a negative Purified Protein Derivative (PPD) test (or equivalent) and
Chest radiography (posteroanterior (PA) and lateral view) at screening. If the subject
has a positive PPD test (or equivalent), has had a past ulcerative reaction of PPD
placement and/or a Chest radiography consistent with prior TB exposure, the subject
must initiate, or have documented completions of a course of anti-Tuberculosis
therapy.
- Patients must undergo screening for Hepatitis B Virus (HBV) (this includes testing for
HBsAg (Hepatitis B surface Antigen), anti-HBs (Hepatitis B surface antibody) and
anti-HBc total (Hepatitis B core antibody total).
- Women of childbearing potential or men capable of fathering children must be using
adequate birth control measures during the study and for 6 months after receiving the
last administration of study agent. Female patients of childbearing potential must
test negative for pregnancy.
- If female, subject is either not of childbearing potential, defined as postmenopausal
for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral
oophorectomy or hysterectomy) or is of childbearing potential and is practicing an
approved method of birth control throughout the study and for 6 months after last dose
of study drug.
Examples of approved methods of birth control include the following:
- Condoms, sponge, foams, jellies, diaphragm or intrauterine device (IUD)
- Oral, parenteral or intravaginal contraceptives for 90 days prior to study drug
administration
- A vasectomized partner
- Subject is judged to be in good health as determined by the principal
investigator based upon the results of medical history, laboratory profile,
physical examination, chest x-ray (CXR), and a 12-lead electrocardiogram (ECG)
performed during screening.
- Subjects must be able and willing to provide written informed consent and comply
with the requirements of this study protocol.
- Subjects must be able and willing to self-administer sc injections or have a
qualified person available to administer subcutaneous injections.
Exclusion Criteria:
- Medical history of inflammatory arthritis of a different etiology other than
peripheral spondyloarthritis (e.g. rheumatoid arthritis, systemic lupus erythematosus,
gout, or any arthritis with onset prior to age 16 years such as Juvenile idiopathic
arthritis (JIA)).
- Prior exposure to any biologic therapy with a potential therapeutic impact on SpA,
including anti-TNF therapy.
- Treatment with any investigational drug of chemical or biological nature within a
minimum of 30 days or 5 half lives (whichever is longer) of the drug prior to the
Baseline Visit.
- Infection(s) requiring treatment with intravenous (iv) anti-infectives within 30 days
prior to the Baseline visit or oral anti-infectives within 14 days prior to the
Baseline Visit.
- Have a known hypersensitivity to human immunoglobulin proteins or other components of
golimumab.
- History of Central Nervous System (CNS) demyelinating disease or neurologic symptoms
suggestive of CNS demyelinating disease.
- History of listeriosis, histoplasmosis, chronic of active Hepatitis B infection,
Hepatitis C infection, human immunodeficiency virus (HIV) infection, immunodeficiency
syndrome, chronic recurring infections or active TB.
- Have a history of, or concurrent, chronic heart failure, including medically
controlled, asymptomatic Congestive Heart Failure (CHF).
- Evidence of dysplasia or history of malignancy (including lymphoma and leukemia) other
than a successfully treated non-metastatic cutaneous squamous cell or basal cell
carcinoma or localized carcinoma in situ of the cervix.
- Have received, or are expected to receive, any live virus or bacterial vaccination
within 3 months prior to the first administration of study agent, during the trial, or
within 6 months after the last administration of study agent.
- Positive pregnancy test at screening or baseline.
- Female subjects who are breast-feeding or considering becoming pregnant during the
study.
- History of clinically significant drug or alcohol abuse in the last 12 months.
- Clinically significant abnormal screening laboratory results as evaluated by the
Investigator.
- Positive rheumatoid factor (RF) or anti-cyclic citrullinated peptide (anti-CCP)
antibody at screening if the titers are crossing 3 times the upper limit of the normal
- Subject is considered by the investigator, for any reason, to be an unsuitable
candidate for the study.
- Subject with diagnosis and current symptoms of fibromyalgia.