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

Giant Cell Arteritis Clinical Trial

— HORTOCI  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01910038
• Other study ID #: Bonnotte PHRC N 2012
• Status: Completed
• Phase: Phase 2
• First received: July 17, 2013
• Last updated: November 29, 2017
• Start date: November 8, 2013
• Est. completion date: June 13, 2016

Study information

• Verified date: November 2017
• Source: Centre Hospitalier Universitaire Dijon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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%.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: June 13, 2016
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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-a, 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 de?ned 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.

Related Conditions & MeSH terms

• Arteritis
• Giant Cell Arteritis
• Polymyalgia Rheumatica

Intervention

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

Locations

Country	Name	City	State
France	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	Hôpital COCHIN	Paris
France	Hôpital La Pitié-Salpêtrière	Paris
France	Institut Mutualiste Montsouris	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire Dijon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Frequency and type of adverse effects encountered		Until Week 52
Secondary	Percentage of relapses		Week 26 and Week 52
Secondary	Time to the first relapse		Until Week 52
Secondary	Factors associated with the occurrence of relapse		Until Week 52
Secondary	The cumulative dose of prednisone.		Weeks 26 and 52