Clinical trial NCT02477059: Effect of the Interleukin-6 Receptor Antagonist Tocilizumab in Patients With Hand Osteoarthritis
Official title: Double-blind, Randomized, Placebo-controlled Trial Evaluating the Effect of Two Infusions Four Weeks Apart of Interleukin-6-Receptor Inhibitor (Tocilizumab) on Pain Relief in Patients With Severe Osteoarthritis of the Hand Refractory to Usual Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hand Osteoarthritis
Keywords: Hand OA
Tocilizumab
Osteoarthritis
Interleukin-6
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Hoffmann-La Roche
First posted: 2015-06-22
Enrollment: 104
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Hand osteoarthritis (HOA) which affects the interphalangeal joints and the metacarpophalangeal of the thumb is a common disease, the prevalence of which being about 30 % of the population over than 70. Some forms of HOA are refractory to usual treatments (analgesics, NSAIDs, local injections) and can lead to a high disability. In vitro and in vivo studies showed that IL-6 is involved in the OA process. The aim of the present study is to assess the efficacy of an Interleukin-6-Receptor Inhibitor (tocilizumab) on pain and function in patients with refractory hand OA.

Detailed description: Patient is randomized to receive investigational product or placebo at week 0 and week 4 (1:1)

* arm 1: 2 infusions four weeks apart of tocilizumab 8mg/kg
* arm 2: 2 infusions four weeks apart of saline solution

Follow-up visits are organized at week 6, and then week 8 and week 12.

Primary outcome is the pain as assessed with the VAS at week 6. Secondary outcomes include morning stiffness duration, patient and practitioner global assessments, functional indexes for hand OA, number of painful joints, number of swollen joints.

110 patients is expected to be randomized in 36 months. Each patient sign an informed consent before the beginning of the study.

Eligibility criteria: Inclusion Criteria:

* Age: 40-85
* Hand OA according to the ACR criteria (with recent X-rays of the hands - less than 6 months )
* Symptomatic hand OA lasting more than 3 months (DIP or PIP) despite analgesics and NSAIDs
* OA affecting more than three finger joints (DIP or PIP) (Kellgren and Lawrence equal or more than 2)
* Pain intensity superior to 40 (VAS 0-100 mm) in the last 24 hours
* Not breastfeeding throughout the study and for 150 days after the last infusion
* Negative pregnancy test or effective contraception for women of childbearing age throughout the study and for 150 days after the last infusion or postmenopausal or surgically sterile
* Written informed consent
* Affiliated to health system

Exclusion Criteria:

* Patients having already been treated with an anti-TNF alpha within 6 months
* Patients having already been treated with an Interleukin-6-Receptor Inhibitor
* Hand OA secondary to inflammatory rheumatism
* Existence of painful syndrome of upper limbs likely to interfere with the monitoring of pain (cervicobrachial neuralgia, incapacitating carpal tunnel syndrome, joint disorders of the elbow or shoulder)
* Inflammatory rheumatism
* Psoriasis
* Contraindications to Interleukin-6-Receptor Inhibitor
* Contraindications to acetaminophen
* Anticoagulant (oral) or treatment with heparin at a curative dose
* Surgery scheduled within 6 months following recruitment
* Local injection of a corticosteroid in a symptomatic finger joint during the previous month
* Local injection of hyaluronic acid in a symptomatic finger joint during the prior 6 months
* Treatment with a slow-acting anti-osteoarthritis agent initiated within the previous 3 months
* Treatment with methotrexate, hydrochloroquine, sulfasalazine, colchicine within the last month
* History of symptomatics sigmoiditis or intestinal ulceration
* Oral corticosteroid within 3 days for hydrocortisone or cortisone, within 8 days for prednisone, prednisolone, methylprednisolone or triamcinolone, and within 12 days for betamethasone or dexamethasone
* Psychiatric illness
* Antidepressants initiated or modified within previous month
* Non-controlled diabetes "mellitus"
* Known viral hepatitis B or C, HIV infection
* Current infectious (active or latent tuberculosis)
* Excessive drinking
* Participation in another search
* Lidocain plasters on digital joint within two months

Primary outcomes:
measure: Change of pain
timeFrame: 6 weeks
Secondary outcomes:
measure: Change of pain
timeFrame: weeks 4, 8, 12
measure: Number of painful joints
timeFrame: weeks 4, 6, 8, 12
measure: Number of swollen joints
timeFrame: weeks 4, 6, 8, 12
measure: Overall assessment of disability
timeFrame: weeks 4, 6, 8, 12
measure: Morning stiffness duration
timeFrame: weeks 4, 6, 8, 12
measure: Evaluation of the function
timeFrame: weeks 4, 6, 8, 12
Other outcomes:
Locations:
city: Paris
country: France
facility: Rheumatology department Lariboisiere Hospital
state: Ile De France
Study officials:
affiliation: Rheumatology department, Lariboisière Hospital
name: Richette Pascal, MD, PhD
role: STUDY_DIRECTOR
References: