GRAVES' ORBITOPATHY MedDRA version: 20.1 Level: LLT Classification code 10057889 Term: Graves' ophthalmopathy System Organ Class: 100000004853
Conditions
Interventions
Trade Name: BENLYSTA - 120 MG - POLVERE PER CONCENTRATO PER SOLUZIONE PER INFUSIONE - USO ENDOVENOSO - FLACONCINO (VETRO) 120 MG 1 FLACONCINO
Product Name: BENLYSTA
Product Code: L04AA26
Pharmaceutica
Sponsors
FONDAZIONE IRCCS CA' GRANDA OSPEDALE MAGGIORE POLICLINICO
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Male or female,18-75 years old; Smokers and non smokers. Women of childbearing potential should use adequate contraception (See “Important Safety Information-Women of Child Bearing Potential” section for specific methods of contraception) during BENLYSTA treatment and for at least 4 months after the last dose. GO at first diagnosis or at the time of relapse, with detectable TSH receptor antibodies. Patients with moderate-severe active GO (clinical activity score 4/10 o 3/7) untreated or previously treated with i.v steroids withdrawn for at least 3 months. Not submitted to previous B cell depleting therapy. Euthyroid for at least 6-8 weeks, on either anti-thyroid medications (tyonamides) to control hyperthyroidism or L-thyroxine for replacement therapy for hypothyroidism. Patients will also be allowed to stay on propranolol treatment for the control of tachycardia. Are the trial subjects under 18? no Number of subjects for this age range: 1 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 35 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: Patients with severe Graves’ orbitopathy (severe keratopathy, compression optic neuropathy and inflammatory optic neuropathy).Treatment with any B cell targeted therapy at any time. Previous oral or intravenous corticosteroid treatment in the last three months not exceeding a cumulative dose of 1 gr. Any immunosuppressant whether biologic or not. Plasmapheresis within 90 days prior to Day 0. Treatment with intravenous immunoglobulin. Azathioprine more than 100 mg/day within 30 days before screening. Administration of live vaccines given within 30 days prior to administration of (Day 0) or concurrently with Belimumab (During study). Splenectomy. Subjects at risk of haemorrhage that threatens a vital organ. History of a major organ transplant or hematopoietic stem cell/marrow transplant. History of malignant neoplasm within the last 5 years, except for adequately treated cancers of the skin (basal or squamous cell) or carcinoma in situ of the uterine cervix. Required management of infections, as follows: currently on any suppressive therapy for a chronic infection, hospitalisation for treatment of infection within 60 days before Day 0, use of parenteral antibiotics within 60 days before Day 0. Pregnancy. Breast feeding. Known coronary artery disease. Significant cardiac arrhythmias. Severe congestive heart failure. Other serious chronic illness. Active infection. History of recurrent clinically significant infection or recurrent bacterial infections. History of sarcoidosis. Primary or secondary immunodeficiency. History of IgE-mediated or non-IgE-mediated hypersensitivity. Known anaphylaxis to mouse-derived proteins. Positive PPD without documentation of treatment for TB infection. Denied consent to HIV testing. Previous orbital radiotherapy, refusal of treatment. Patients with known allergy to paracetamol, difenidramine, hydrocortisone. Patients positive for HBsAg. Patients positive for HBcAb regardless of HBsAb status will undergo HBV DNA which if positive will be excluded. Patients positive at screening Hepatitis C antibody. Positive test for Human Immunodeficiency Virus (HIV) antibody at screening or historically. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) greater or equal to 3x upper limit of normal (ULN). Alkaline phosphatase and bilirubin >2xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin is<35%). Grade 3 / 4 IgG deficiency and IgA deficiency (IgA < 10mg/dL). Lymphocyte count<500/mm3. History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy including a previous anaphylactic reaction to parenteral administration contrast agents, human or murine proteins or monoclonal antibodies. Major depression. Have evidence of serious suicide risk including any history of suicidal behavior in the last 6 months and/or any suicidal ideation in the last 2 months or who in the investigator's judgment, pose a significant suicide risk. Current drug or alcohol abuse or dependence.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1) efficacy of therapy on the active inflammatory phase of GO and the progression of the eye disease. 2) efficacy of therapy in inducing remission of hyperthyroid GD and in reducing the frequency and the degree of hyperthyroidism relapses at the end of anti-thyroid treatment. ;Secondary Objective: effects of belimumab on the target tissues of GD (the thyrocytes) and GO (the eye muscles, orbital fat and connective tissue) and on thyroid and orbital infiltrating immune cells.;Primary end point(s): 1. Decrease of the clinical activity score (CAS) of 2 points or disease inactivation (CAS<4) in active GO patients at 12, 24, 36 and 48 weeks from belimumab or methylprednisolone administration. 2. Safety of belimumab therapy in patients with GD and GO. ;Timepoint(s) of evaluation of this end point: 12-24-36-48 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. decrease of GO severity by NOSPECS classes 2 or 3 or 4 of at least 1 point; 2. analysis of the rate of response to therapy and of relapse of active disease at 12, 24, 36 and 48 weeks; 3. time (months) to remission of hyperthyroidism and decrease or negativeness of serum TSH receptor antibodies in patients with hyperthyroid GD at ,12, 24, 36 and 48 weeks; 4. quantification of signs of residual motility abnormalities by motility tests and analysis of quality of life (GO-QoL) 5. analysis of intrathyroidal and orbital tissue and lymphocyte BAFF expression after therapy by immunohistochemistry and cytofluorimetry. ;Timepoint(s) of evaluation of this end point: 12, 24, 36, 48 weeks | — |
Countries
Italy
Contacts
Public ContactU.O.C. ENDOCRINOLOGIA E DIABETOLOGI
FONDAZIONE IRCCS CA' GRANDA OSPEDALE MAGGIORE POLICLINICO
Outcome results
None listed