Thyroid-Associated Ophthalmopathy / Graves' Ophthalmopathy
Conditions
Interventions
Product Name: Teprotumumab
Product Code: RV 001
Pharmaceutical Form: Concentrate for solution for infusion
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the plac
Sponsors
River Vision Development Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Aged 18-75 years (inclusive). 2. Clinical diagnosis of Graves' disease associated with moderate to severe active TED with a clinical activity score (CAS) = 4 (on the 7 point version of the scale) for the most severely affected eye. 3. Fewer than 9 months from onset of TED as determined by patient records. 4. No previous medical or surgical therapy for TED, excluding local supportive measures and oral steroids if the maximum cumulative dose is less than 1000 mg methylprednisolone or equivalent. There must be at least 6 weeks between last administration of steroids and study randomization. 5. Patients must be euthyroid or with mild hypo- or hyperthyroidism defined as free thyroxine (FT4) and free triiodothyronine (FT3) levels less than 50% above or below the normal limits. Every effort should be made to correct the mild hypo- or hyperthyroidism promptly. 6. Not requiring immediate surgical ophthalmological intervention. 7. ALT/AST = 3 x the upper limit of normal (ULN) for the reference laboratory; serum creatinine =65 years) yes F.1.3.1 Number of subjects for this age range 6
Exclusion criteria
Exclusion criteria: 1. Decreased best corrected visual acuity due to optic neuropathy as defined by a decrease in vision within the last 6 months of two lines of Snellen chart, new visual field defect or color defect secondary to optic nerve involvement. 2. Corneal decompensation unresponsive to medical management. 3. Improvement in CAS of = 2 points between screening and baseline. 4. 4. Treatment with oral or intravenous (IV) steroids within the previous 3 months except oral steroids for the treatment of TED with a cumulative dose less than 1000 mg methylprednisolone or equivalent providing there is a 6 week washout prior to study randomization. Administration of any other immunosuppressive agent for any indication in the previous 3 months. Topical steroids for dermatological conditions are not excluded. 5. Any treatment with any investigational agent for any condition in the past 60 days, or treatment with an investigational agent for any condition during the trial. 6. Any previous treatment with rituximab (Rituxan® or MabThera®). 7. Previous orbital irradiation. 8. Identified preexisting ophthalmic disease which, in the judgment of the investigator, would preclude study participation or complicate interpretation of study results. 9. Platelet count 2 gr/dL below the lower limit of the local laboratory reference range. 12. Malignant condition in the past 12 months (with the exception of successfully treated basal cell carcinoma of the skin) 13. Pregnant or lactating women. 14. Drug or alcohol abuse, or history of either within the previous 2 years, in the opinion of the investigator or as reported by the patient. 15. Poorly controlled diabetes. 16. Known hypersensitivity to any of the components of RV 001 or prior hypersensitivity reactions to monoclonal antibodies. 17. Any other condition which, in the opinion of the investigator, would preclude inclusion in the study. 18. Patients who have already been randomized and received treatment under this protocol. Under no circumstances are patients who enroll in this study permitted to be re-randomized to this study and enrolled for a second course of treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary efficacy endpoint is the assessment of whether the patient is a responder or not at the end of the 6 month treatment phase.;Secondary Objective: CAS, motility, proptosis, clinical measures of severity, time to response and GO-QOL;Primary end point(s): The primary efficacy endpoint is the assessment of whether the patient is a responder or not (yes or no) at the end of the 6 month treatment phase (week 24). A responder is defined as a patient with a decrease in overall CAS = 2 points, OR an improvement in ductions of = 10 degrees, OR a reduction in proptosis = 2 mm. All responses must be observed in the study eye without deterioration of CAS in the fellow eye (i.e. increase in CAS = 2 points).;Timepoint(s) of evaluation of this end point: End of the 6 month treatment phase. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety will be assessed by adverse events (AEs), including serious AEs (SAEs), premature withdrawals for AEs, rates of AEs (severity, relationship), ECGs, vital signs, physical examination, laboratory parameters (hematology, biochemistry, urinalysis).;Timepoint(s) of evaluation of this end point: End of the 6 month treatment phase. | — |
Countries
Germany, Italy, Netherlands, United Kingdom, United States
Contacts
Public ContactSerge Kosobokovs
Premier Research Group Ltd
Outcome results
None listed