Infliximab Biosimilar in Takayasu's Arteritis

NCT ID: NCT03192878

Last Updated: 2017-06-20

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 30 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-03-01
• Study Completion Date: 2019-07-31

Brief Summary

Takayasu arteritis (TA) is a chronic inflammatory disease affecting large and medium caliber arteries, particularly the aortic arch and its main branches. Clinical manifestations are caused by the marked thickening of the wall of the involved vessels, resulting in lumen narrowing and ischemia of the tributary districts. Therapy is based on the use of corticosteroids, immunosuppressants, and biologic drugs including infliximab, a monoclonal antibody blocking tissue necrosis factor (TNF)-alpha. Biosimilar infliximab is commercially available and used in the treatment of various immune-mediated conditions. There are currently no data on the efficacy and safety of biosimilar infliximab in the treatment of TA.

The investigators propose this monocentric, observational, prospective, open label study to evaluate the efficacy and safety of biosimilar infliximab in the treatment of 30 patients with TA. Specifically, the study will include: I) TA patients refractory to treatment with corticosteroid and/or immmunosuppressive therapy, not previously treated with infliximab; II) TA patients already receiving treatment with originator infliximab.

Biosimilar infliximab will be administered at dosages usually employed in the treatment of TA. Specifically, patients not previously treated with the originator drug will receive biosimilar infliximab intravenously at a dose of 5 mg/Kg at time 0, at week 2, at week 4; thereafter, treatment will be administered every 4-6 weeks at a dose of 5-10 mg/kg based on clinical judgement. In patients previously treated with the originator drug, biosimilar infliximab will be administered at the same dosages.

To evaluate the efficacy of therapy, changes in clinical manifestations, laboratory examinations, and imaging findings including angio-magnetic resonance imaging (MRI) of thoracic and abdominal vessels and total body PET/CT scan will be evaluate at time 0 as well as 6 and 12 months following treatment initiation. In order to evaluate the safety of the study treatment, the investigators will stringently evaluate possible side effects of treatment, including infusion reactions, changes in laboratory tests, infection, cancer, autoimmune manifestations, neurological and cardiovascular symptoms.

The total duration of follow up for each patient will be 52 weeks from enrolment.

Conditions

Takayasu Arteritis

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

Naive patients

Patients with corticosteroid- and/or traditional immunosuppressive drug-resistant Takayasu's arteritis with indication of initiating therapy with anti-TNF-alpha

Infliximab

Intervention Type: DRUG

infliximab biosimilar

Switch patients

Patients with Takayasu's arteritis already in therapy with infliximab originator (Remicade) in whom the originator therapy will be replaced with infliximab biosimilar therapy

Infliximab

Intervention Type: DRUG

infliximab biosimilar

Interventions

Infliximab

infliximab biosimilar

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• age> 18 years;
• negative pregnancy test;
• use of a reliable contraceptive method by all potentially fertile patients during the study and for the six months following the end of therapy;
• diagnosis of TA according to the Classification criteria of the American College of Rheumatology 1990;
• Multifocal vascular aortic and arterial involvement as evaluated by imaging examinations (angiography / angio-MRI / vascular ecocolordoppler / PET);
• failure to respond to corticosteroid therapy after 6-8 weeks of prednisone therapy at a dose of 1 mg / Kg per day, or impossibility to reduce the dose of prednisone to 0.5 mg / Kg within 3 months of initiation of therapy and to less than 0.2 mg / kg per day within 6 months of initiation of therapy (may also include patients who, despite receiving combination therapy with prednisone and cyclophosphamide, azathioprine, methotrexate, cyclosporin A, mycophenolate mofetil, leflunomide and rapamycin for at least 3 months, could not reduce the prednisone dose to 0.5 mg / Kg per day within 3 months of initiation of therapy, or to less than 0.2 mg / kg per day within 6 months of initiation of therapy);
• ongoing anti-TNF-alpha treatment with originator infliximab (inclusion criterion for the switch arm).

Exclusion Criteria

• history of lymphoproliferative disease or solid neoplasm in the last 5 years, with the exception of successfully treated and completely resolved squamous cell skin carcinoma;
• history of uncontrolled diabetes, unstable cardiac ischaemia, congestive heart failure (NYHA class III and IV), active intestinal inflammatory disease, active peptic ulcer, recent stroke (within 3 months) and any other pathological conditions that, according to the treating physician, could expose the subject to the risk of adverse events;
• serological tests for hepatitis B or C indicating an active infection;
• history of HIV infection;
• chronic infection, or severe infections requiring hospitalization or intravenous antibiotic treatment within 30 days prior to inclusion in the study, or requiring treatment with oral antibiotics within 14 days prior to enrollment;
• ongoing pregnancy or lactation;
• history of drug or alcohol abuse;
• Previous diagnosis or signs of demyelinating disease of the central nervous system;
• history of active tuberculosis, histoplasmosis or listeriosis;
• previous infection with M. tuberculosis (as documented by chest x-rays and / or positive quantiferon test), in which case patients will only be enrolled after initiating prophylactic therapy according to current guidelines.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ospedale San Raffaele

OTHER

Sponsor Role: lead

Responsible Party

Lorenzo Dagna

Head, Unit of Immunology, Rheumatology, Allergy and Rare Diseases

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Lorenzo Dagna, MD

Role: PRINCIPAL_INVESTIGATOR

IRCCS H San Raffaele

Locations

IRCCS Ospedale San Raffaele

Milan, MI, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Elena M Baldissera, MD

Role: CONTACT

baldissera.elena@hsr.it

+39022643 ext. 7254

Giulio Cavalli, MD

Role: CONTACT

cavalli.giulio@hsr.it

+39022643 ext. 4683

Facility Contacts

Elena M Baldissera, MD

Role: primary

baldissera.elena@hsr.it

+39022643 ext. 7254

Giulio Cavalli, MD

Role: backup

cavalli.giulio@hsr.it

+39022643 ext. 4683

Other Identifiers

TakaSim

Identifier Type: -

Identifier Source: org_study_id