Evaluation of Tocilizumab as an add-on Therapy to Corticoids in Giant Cell Arteritis: Proof of Concept Study.

NCT ID: NCT01910038

Last Updated: 2017-11-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-11-08
• Study Completion Date: 2016-06-13

Brief Summary

It has been reported that around 40% of GCA patients are able to decrease the prednisone dose until 0.1 mg/Kg/d or less after 6 months of treatment. In this study, we hypothesized that adding 3 months of tocilizumab to prednisone could increase the percentage from 40 to 70%.

Conditions

Giant Cell Arteritis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Prednisone+Tocilizumab

Prednisone (0.7 mg/Kg/d and then progressively tapered to reach 0.1 mg/Kg/d at W24) + tocilizumab 8mg/Kg/4 weeks for a total of 4 infusions (S0, S4, S8, S12).

Group Type: EXPERIMENTAL

corticoids+ tocilizumab 8mg/Kg/4 weeks

Intervention Type: DRUG

Interventions

corticoids+ tocilizumab 8mg/Kg/4 weeks

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age > 50 years
• GCA fulfilling ≥3/5 ACR criteria
• Newly diagnosed GCA or relapsing GCA if treatments (Glucocorticoids±immunosuppressants) have been stopped for at least 6 months
• Glucocorticoids started for less than 21 days
• Proof of large vessel vasculitis:

• Positive temporal artery biopsy (TAB)
• Aortitis, as defined by regular circumferential wall thickening ≥3mm in the absence of calcification and/or significant atheroma on angio-CT images; or a homogeneous vascular signal more intense than the liver on 18FDG-PET images.
• For men and women of a child-bearing age, an effective method of contraception must be used by the patient or his or her partner throughout the treatment with tocilizumab (or placebo) and for 3 months after the end of the treatment. Breast-feeding is not authorised until 3 months after the end of treatment with tocilizumab. Women not considered at risk of pregnancy are those defined by menopause of at least one year or surgically steriles (ligature of the fallopian tubes, bilateral ovariectomy or hysterectomy)
• Persons who have provided written informed consent
• Persons covered by the National Health Insurance Agency

Exclusion Criteria

• Pregnancy
• hospitalization in the previous year for drug or alcohol intoxication
• current treatment for another autoimmune or inflammatory disease
• known hypersensitivity to TCZ or one of its excipients or another human or murine monoclonal antibody
• treatment with anti-TNF-α, methotrexate, cyclophosphamide, dapsone, methylprednisolone pulses or any other immunosuppressive or immunomodulatory drug or biotherapy within 6 months before inclusion
• long-course systemic GC therapy
• prednisone therapy >1 mg/kg/day, whatever the duration
• serious or chronic proven infections requiring hospitalization or intravenous antibiotics within 30 days before inclusion
• other proven infections that required antibiotics within 14 days before inclusion
• opportunistic infections
• evidence of active tuberculosis or latent tuberculosis (as defined by a positive interferon gamma release assay)
• active chronic hepatitis B or C or HIV
• cancer or lymphoproliferative disorders within the 5 years before inclusion (with the exception of in situ cervical cancer and squamous or basal cell carcinoma with R0 resection)
• past history of sigmoid diverticulitis
• any active hepatic disease
• hepatic failure; thrombocytopenia <50 G/L
• neutropenia <0.5 G/L
• history of moderate to severe congestive heart failure or demyelinating disease
• recent stroke
• current signs or symptoms of severe, progressive, or uncontrolled disease, not due to GCA, which contraindicates TCZ
• severe and uncontrolled hypercholesterolemia
• high cardiovascular risk (former cerebral or coronary vascular event, or vascular risk >20% at 10 years according to the Framingham risk score [24]); dementia; non-compliant patients
• patients under ward of court, tutelage or legal guardianship.

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Hospitalier Universitaire Dijon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

CHU de Caen - Hôpital Côte de Nacre

Caen, , France

CHU de Dijon

Dijon, , France

Chu Dupuytren

Limoges, , France

Hôpital Edouard HERRIOT

Lyon, , France

Hôpitaux privés de Metz - Site Sainte Blandine

Metz, , France

Institut Mutualiste Montsouris

Paris, , France

Hôpital La Pitié-Salpêtrière

Paris, , France

Hôpital COCHIN

Paris, , France

Countries

France

References

Samson M, Devilliers H, Ly KH, Maurier F, Bienvenu B, Terrier B, Charles P, Guillevin L, Besancenot JF, Liozon E, Fauchais AL, Loffroy R, Binquet C, Audia S, Seror R, Mariette X, Bonnotte B. Tocilizumab as an add-on therapy to glucocorticoids during the first 3 months of treatment of Giant cell arteritis: A prospective study. Eur J Intern Med. 2018 Nov;57:96-104. doi: 10.1016/j.ejim.2018.06.008. Epub 2018 Jul 24.

Reference Type: DERIVED

PMID: 30054122 (View on PubMed)

Other Identifiers

Bonnotte PHRC N 2012

Identifier Type: -

Identifier Source: org_study_id