Evaluation of Tocilizumab as an add-on Therapy to Corticoids in Horton's Disease: Proof of Concept Study. (HORTOCI)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified July 2013 by Centre Hospitalier Universitaire Dijon
Sponsor:
Information provided by (Responsible Party):
Centre Hospitalier Universitaire Dijon
ClinicalTrials.gov Identifier:
NCT01910038
First received: July 17, 2013
Last updated: July 25, 2013
Last verified: July 2013
  Purpose

The usual percentage of patients receiving 0.1 mg/Kg/d or less of prednisone after 6 months of treatment is approximately 40%. We believe that adding tocilizumab to the corticotherapy in this protocol could increase the percentage from 40 to 70%.

From an immunological point of view, we believe we will see not only a fall in the Th17 response (as with corticoids alone), but also a rise in Treg lymphocytes.


Condition Intervention Phase
Horton's Disease
Drug: corticoids+ tocilizumab 8mg/Kg/month
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by Centre Hospitalier Universitaire Dijon:

Primary Outcome Measures:
  • Percentage of Treg [ Time Frame: baseline ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: September 2013
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
corticoids+ tocilizumab Drug: corticoids+ tocilizumab 8mg/Kg/month

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age > 50 ans
  • Diagnosis of Horton's disease defined according to ACR criteria (annex 1).
  • Newly-diagnosed disease and corticotherapy started for less than 14 days (exceptionally, + 7 additional days in case of a delay in obtaining results of the BAT)
  • Biopsy of the temporal artery (TAB) compatible with the diagnosis of HD: non-necrotising giant-cell arteritis with a granulomatous inflammatory infiltrate, usually located at the intima-media junction, made up of lymphocytes, macrophages and multinucleated giant cells; or at least evidence of a chronic inflammatory infiltrate made up of lymphocytes and a few neutrophils or eosinophils without giant cells.
  • 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
  • Dementia syndrome
  • Non-observant patients
  • Patient living more than 150 km from the investigating centre
  • Negative temporal artery biopsy
  • History of alcohol abuse or drug abuse leading to hospitalisation in the previous year
  • Patient followed and/or treated for another known auto-immune or inflammatory disease
  • Hypersensitivity to tocilizumab or to one of its excipients
  • Persons under protection of the court or guardianship
  • Treatments:

Patients already being treated (or who stopped treatment less than 6 months earlier), for Horton Disease or for another disease, Treatment with anti TNF-α, methotrexate, ciclosporin, cyclophosphamide, dapsone or bolus of corticoids. Patients on long-term corticoids for another disease Start of treatment for Horton's disease with one dose > 1 mg/Kg whatever the duration

- Infections: Chronic (or acute) viral hepatitis B or C Infection with HIV Persistent or severe infection requiring hospitalisation or IV antibiotherapy during the 30 days preceding inclusion Infection requiring oral antibiotics in the 14 days preceding inclusion History of active tuberculosis, histoplasmosis or listeriosis Signs of latent tuberculosis (based on a history of untreated contact, opacity of more than 1 cm in diameter on a lung X-ray, or a positive in vitro test (Quantiferon Gold or T-Spot-TB) History of sigmoiditis complicating diverticulosis, a history of peritonitis

  • Unstable disease: uncontrolled diabetes with a history of recurrent infections, unstable ischemic heart disease, Heart failure ≥ stage III/IV of the New York Heart Association , recent cerebrovascular accident, or any other severe disease that may, because of participation in the study and in the opinion of the investigator, lead to a risk for the patient.
  • Patients with a vascular risk Patients with a high cardiovascular risk: proven history of coronary artery disease or vascular disease, type 2 diabetes with a high cardiovascular risk *, vascular risk >20% at 10 years (Framingham equation) Severe dyslipidemia not controlled by lipid-lowering treatment
  • Active liver disease and hepatocellular insufficiency
  • Neutropenia (<500/mm3) or thrombopenia (<50 000/mm3)
  • Demyelinating disease of the central nervous system (current or past)
  • Neoplasia of less than 5 years, except skin cancer (other than melanoma) with complete R0 resection
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01910038

Locations
France
CHU de Dijon Not yet recruiting
Dijon, France, 21079
Contact: Maud CARPENTIER    03.80.29.35.10    maud.carpentier@chu-dijon.fr   
Principal Investigator: Bernard BONNOTTE         
Sponsors and Collaborators
Centre Hospitalier Universitaire Dijon
  More Information

No publications provided

Responsible Party: Centre Hospitalier Universitaire Dijon
ClinicalTrials.gov Identifier: NCT01910038     History of Changes
Other Study ID Numbers: Bonnotte PHRC N 2012
Study First Received: July 17, 2013
Last Updated: July 25, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Polymyalgia Rheumatica
Giant Cell Arteritis
Muscular Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Vasculitis, Central Nervous System
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Arteritis
Vascular Diseases
Cardiovascular Diseases
Vasculitis
Skin Diseases, Vascular
Skin Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on September 18, 2014