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

Phase 2

Completed

• Conditions: Giant Cell Arteritis
• Interventions: Drug: corticoids+ tocilizumab 8mg/Kg/4 weeks

• Registration Number: NCT01910038
• Lead Sponsor: Centre Hospitalier Universitaire Dijon

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%.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-07-17
• Study First Submitted QC: 2013-07-25
• Study First Posted: 2013-07-29
• Study Start: 2013-11-08
• Primary Completion: 2015-12
• Study Completion: 2016-06-13
• Status Verified: 2017-11
• Last Update Submitted: 2017-11-29
• Last Update Posted: 2017-11-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Prednisone+Tocilizumab	corticoids+ tocilizumab 8mg/Kg/4 weeks	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).

Primary Outcome Measures

Name	Time	Method
Percentage of patients in remission with a dose of prednisone ≤ 0.1 mg/kg/day	Week 26	Remission: absence of symptoms attributable to Giant Cell Arteritis and normalization of inflammatory markers (CRP\<10 mg/L and ESR\<30 mm/h).; Relapse: recurrence of symptoms attributable to active GCA and/or increased levels of inflammatory markers (CRP≥10 mg/L and/or ESR≥30 mm/h). Elevation of inflammatory markers in the absence of GCA symptoms was considered relapse if it persisted at two time points at 1 week apart without any other obvious etiology than GCA.

Secondary Outcome Measures

Name	Time	Method
Percentage of relapses	Week 26 and Week 52
The cumulative dose of prednisone.	Weeks 26 and 52
Time to the first relapse	Until Week 52
Factors associated with the occurrence of relapse	Until Week 52
Frequency and type of adverse effects encountered	Until Week 52

Trial Locations

Locations (8)

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