Clinical trial NCT01910038: Evaluation of Tocilizumab as an add-on Therapy to Corticoids in Giant Cell Arteritis: Proof of Concept Study.
Official title: Evaluation of Tocilizumab as an add-on Therapy to Corticoids in Giant Cell Arteritis: Proof of Concept Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Giant Cell Arteritis
Lead sponsor: Centre Hospitalier Universitaire Dijon
Sponsor class: OTHER
First posted: 2013-07-29
Enrollment: 20
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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%.


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.

Primary outcomes:
measure: Percentage of patients in remission with a dose of prednisone ≤ 0.1 mg/kg/day
timeFrame: Week 26
Secondary outcomes:
measure: Frequency and type of adverse effects encountered
timeFrame: Until Week 52
measure: Percentage of relapses
timeFrame: Week 26 and Week 52
measure: Time to the first relapse
timeFrame: Until Week 52
measure: Factors associated with the occurrence of relapse
timeFrame: Until Week 52
measure: The cumulative dose of prednisone.
timeFrame: Weeks 26 and 52
Other outcomes:
Locations:
city: Caen
country: France
facility: CHU de Caen - Hôpital Côte de Nacre
city: Dijon
country: France
facility: CHU de Dijon
city: Limoges
country: France
facility: Chu Dupuytren
city: Lyon
country: France
facility: Hôpital Edouard HERRIOT
city: Metz
country: France
facility: Hôpitaux privés de Metz - Site Sainte Blandine
city: Paris
country: France
facility: Institut Mutualiste Montsouris
city: Paris
country: France
facility: Hôpital La Pitié-Salpêtrière
city: Paris
country: France
facility: Hôpital COCHIN
Study officials:
References:
citation: 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.