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

NCT01910038 | Completed Phase 2

• 1 other identifier: Bonnotte PHRC N 2012
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 8

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

Outcome Measures

Primary Outcomes (1)

• Percentage of patients in remission with a dose of prednisone ≤ 0.1 mg/kg/day

  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.

  Week 26

Secondary Outcomes (5)

• Frequency and type of adverse effects encountered

  Until Week 52

• Percentage of relapses

  Week 26 and Week 52

• Time to the first relapse

  Until Week 52

• Factors associated with the occurrence of relapse

  Until Week 52

• The cumulative dose of prednisone.

  Weeks 26 and 52

Study Arms (1)

Prednisone+Tocilizumab

EXPERIMENTAL

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).

Drug: corticoids+ tocilizumab 8mg/Kg/4 weeks

Interventions

corticoids+ tocilizumab 8mg/Kg/4 weeks DRUG

Prednisone+Tocilizumab

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• long-course systemic GC therapy
• prednisone therapy \>1 mg/kg/day, whatever the duration
• 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
• 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

Sponsors & Collaborators

• Centre Hospitalier Universitaire Dijon: lead

Study Sites (8)

CHU de Caen - Hôpital Côte de Nacre

Caen, 14033, France

Location

CHU de Dijon

Dijon, 21079, France

Location

Chu Dupuytren

Limoges, 87042, France

Location

Hôpital Edouard HERRIOT

Lyon, 69437, France

Location

Hôpitaux privés de Metz - Site Sainte Blandine

Metz, 57045, France

Location

Institut Mutualiste Montsouris

Paris, 75014, France

Location

Hôpital La Pitié-Salpêtrière

Paris, 75651, France

Location

Hôpital COCHIN

Paris, 75679, France

Location

Related Publications (1)

• 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.

  PMID: 30054122 DERIVED

MeSH Terms

Conditions

Giant Cell Arteritis

Condition Hierarchy (Ancestors)

Vasculitis, Central Nervous System; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arteritis; Vasculitis; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2013
• First Posted: July 29, 2013
• Study Start: November 8, 2013
• Primary Completion: December 1, 2015
• Study Completion: June 13, 2016
• Last Updated: November 30, 2017

Record last verified: 2017-11

Locations

FR (8)