Thyroid eye disease (TED) MedDRA version: 20.0 Level: SOC Classification code 10015919 Term: Eye disorders System Organ Class: 10015919 - Eye disorders MedDRA version: 20.1 Level: PT Classification code 10060742 Term: Endocrine ophthalmopathy System Organ Class: 10015919 - Eye disorders MedDRA version: 20.1 Level: LLT Classification code 10072802 Term: Thyroid associated orbitopathy System Organ Class: 10015919 - Eye disorders MedDRA version: 20.1 Level: LLT Classification code 10057889 Term
Conditions
Interventions
Product Name: Linsitinib
Product Code: [ASP7487, OSI-906]
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Linsitinib
CAS Number: 867160-71-2
Current Sponsor code: ASP7487, OSI-906
Other d
Sponsors
VasaraGen, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects must be =18 years of age at Screening. 2. Clinical diagnosis of Graves' Disease and/or autoimmune Hashimoto's thyroiditis associated with active moderate to severe TED with a CAS = 4 for the most severely affected eye at Screening and Baseline. 3. Moderate-to-severe active TED with onset within 12 months prior to the Baseline visit and usually associated with one or more of the criteria described in the protocol. 4. Subjects must be euthyroid or, have subclinical hyperthyroidism. 5. Does not require immediate surgery, radiotherapy or other ophthalmological intervention at the time of Screening and is not planning for any such treatment during the course of the study. 6. Diabetic subjects must have HbA1c =65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: 1. Decreased best corrected visual acuity due to optic neuropathy as defined by a decrease in vision of 2 lines on the Snellen chart, new visual field defect, or color defect secondary to optic nerve involvement within the last 6 months. 2. Corneal decompensation unresponsive to medical management. 3. Decrease in CAS of = 2 points in the primary study eye between Screening and Baseline. 4. Decrease in proptosis of = 2 mm in the primary study eye between Screening and Baseline. 5. Previous orbital irradiation or surgery. 6. Prior IGF-1R inhibitor therapy for any condition. 7. Any steroid use (intravenous [IV] or oral) with a cumulative dose equivalent to > 1g of methylprednisolone or equivalent for the treatment of TED within 3 months of Screening. 8. Corticosteroid use (including topical) for conditions other than TED within 4 weeks prior to Screening. 9. Use of any other non-steroid immunosuppressive agent within 4 weeks prior to Screening. 10. Any previous treatment with anti-IL6 receptor, anti- CD20, (MS4A1) antibodies or monoclonal antibody for immunomodulation within the past 9 months prior to Screening. 11. Selenium and/or biotin use as a treatment for TED within 3 weeks prior to screening is disqualifying, not allowed and must not be restarted during the clinical trial or Follow-up period. 12. Identified pre-existing ophthalmic or other disease that in the judgement of the Investigator, would preclude study participation or complicate interpretation of study results. 13. Ocular surgery other than routine cataract surgery or subsequent YAG laser capsulotomy. 14. Biopsy-proven or clinically suspected inflammatory bowel disease (e.g., diarrhea with or without blood or rectal bleeding associated with abdominal pain or cramping/colic, urgency, tenesmus, or incontinence for more than 4 weeks without a confirmed alternative diagnosis OR endoscopic or radiologic evidence of enteritis/colitis without a confirmed alternative diagnosis). 15. History of QTcF prolongation; or QTcF prolongation at Screening. 16. Use of drugs causing QT interval prolongation within 14 days prior to Day 1 dosing. 17. Bleeding diathesis that in the judgment of the Investigator would preclude inclusion in the clinical trial. 18. Laboratory values as described in the protocol. 19. Malignant conditions being actively treated or treated in the past 12 months (with the exception of successfully treated basal cell of the skin). Recent (within 3 months of Screening) basal cell of the eyelid skin is excluded. See the full list in the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to study the effect of two doses of linsitinib versus placebo on the proptosis responder rate at Week 24. ;Secondary Objective: 1. Evaluate the effect of linsitinib versus placebo on the mean change from Baseline to Week 24 in proptosis measurement in the primary study eye. 2. Evaluate the effect of linsitinib versus placebo on the diplopia responder rate at Week 24. 3. Evaluate the effect of linsitinib versus placebo on the overall responder rate in CAS or proptosis in the contralateral non-study eye at Week 24. 4. Evaluate the effect of linsitinib versus placebo on the percentage of subjects with a CAS value of 0 or 1 at Week 24 in the primary study eye. 5. Evaluate the effect of linsitinib versus placebo on the mean change from Baseline to Week 24 in the Graves’ Ophthalmopathy Quality of Life (GO-QoL) questionnaire overall score. ;Primary end point(s): Rate of effect of linsitinib versus placebo on the proptosis responder rate at Week 24. ;Timepoint(s) of evaluation of this end point: At week 24. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Mean change from Baseline to Week 24 in proptosis measurement in the primary study eye. 2. Diplopia responder rate. 3. Overall responder rate. 4. Percentage of subjects with a CAS value of 0 or 1 at Week 24 in the primary study eye. 5. Mean change from Baseline to Week 24 in the Graves' Ophthalmopathy Quality of Life (GO-QoL) questionnaire overall score.;Timepoint(s) of evaluation of this end point: At week 24 | — |
Countries
Canada, Germany, Italy, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trials
VasaraGen, Inc.
Outcome results
None listed