Effect of the Interleukin-6 Receptor Antagonist Tocilizumab in Patients With Hand Osteoarthritis (TIDOA)

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

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.

Study Overview

• Status: Completed
• Conditions: Hand Osteoarthritis
• Intervention / Treatment: Drug: tocilizumab; Drug: saline solution

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.

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Ile De France
    • Paris, Ile De France, France, 75010
      • Rheumatology Department Lariboisière Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: tocilizumab; 2 infusions four weeks apart	Drug: tocilizumab; Le tocilizumab is administered by intravenous infusion at a dose of 8 mg / kg.; Other Names: ROACTEMRA®
Placebo Comparator: saline solution; 2 infusions four weeks apart	Drug: saline solution; La saline solution is administered by intravenous infusion.; Other Names: NaCl 0,9 %

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of pain	Change of pain between the first infusion (week 0) and 2 weeks after the second infusion (week 6) as assessed on the VAS (0 -100 mm)	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of pain	Change of pain between the first infusion (week 0) and 4, 8,12 weeks after the first infusion as assessed on the VAS (0 -100 mm)	weeks 4, 8, 12
Number of painful joints		weeks 4, 6, 8, 12
Number of swollen joints		weeks 4, 6, 8, 12
Overall assessment of disability	Patient and practitioner global assessments	weeks 4, 6, 8, 12
Morning stiffness duration		weeks 4, 6, 8, 12
Evaluation of the function	Dreiser's algofunctional index + Functional Cochin hand index	weeks 4, 6, 8, 12

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Hoffmann-La Roche
• Investigators: Study Director: Richette Pascal, MD, PhD, Rheumatology department, Lariboisière Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2015
• Primary Completion (Actual): December 26, 2018
• Study Completion (Actual): February 1, 2019

Study Registration Dates

• First Submitted: June 10, 2015
• First Submitted That Met QC Criteria: June 17, 2015
• First Posted (Estimate): June 22, 2015

Study Record Updates

• Last Update Posted (Actual): July 30, 2019
• Last Update Submitted That Met QC Criteria: July 29, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Osteoarthritis; Tocilizumab; Interleukin-6; Hand OA
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis
• Other Study ID Numbers: P120206