Participants are excluded from the study if any of the following criteria apply:

Medical Conditions

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 before screening. 

2. Monocular vision: defined as best corrected visual acuity less than 20/400 in the fellow eye, or a serious ocular condition in the fellow eye that could lead to worsening of vision. 

3. Corneal decompensation unresponsive to medical management. 

4. Previous orbital irradiation or surgery for TED (eg, orbital decompression surgery or strabismus surgery). 

5. Identified pre-existing ophthalmic disease that, in the judgment of the investigator, would preclude study participation or confound interpretation of study results. 

6. CAS <4 at screening or baseline, or a decrease in CAS of ≥2 points between screening and baseline in the study eye. 

7. Proptosis (exophthalmos) <3 mm above the normal range (based upon race and gender) per investigator judgement for the most severely affected eye at screening or baseline or decrease in proptosis of ≥2 mm between screening and baseline in the study eye. 

8. Anticipated need for rescue therapy/intervention during Period A (Primary Efficacy Period) due to sight-threatening complications or other significant and acute deterioration in vision. Examples of significant and acute visual deterioration include (but not limited to): decrease in best corrected visual acuity by 2 or more lines assessed with the Snellen chart over the course of the study, new visual field defect, or color defect secondary to optic nerve involvement. 

9. Uncontrolled thyroid disease. Participants must be euthyroid or have mild hypo- or hyperthyroidism (defined as FT4 and FT3 levels <50% above or below the normal limits). The thyroid disease must not be associated with any clinically significant or unstable symptoms or complications other than TED at screening. 

10. Immunodeficiency (genetic or acquired, such as acquired immunodeficiency syndrome, common variable immunodeficiency, etc). 

11. Serious infection (defined as an infection requiring hospitalization and/or IV antibiotic, IV antifungal, or IV antiviral treatment and/or having a clinical presentation that is viewed by the investigator as consistent with a serious infection) within the past 6 months prior to the Baseline (Day 1) visit, or more than 1 such episode over the past 24 months prior to the baseline visit. (Day 1). 

12. Presence of a transplanted organ. 

13. Current evidence of latent or active TB infection by QuantiFERON Gold or residing with or frequent close contact with individual(s) with active TB. 

14. Currently active medically significant opportunistic infection or history of serious opportunistic infection within 12 months prior to the Baseline visit (eg, cytomegalovirus, pneumocystis pneumonia, aspergillus, histoplasma, coccidioidomycosis, mpox, non-TB mycobacterium; not including localized thrush due to corticosteroid therapy or other localized yeast infection without complications). 

15. Any prior history of or current thromboembolic event (includes thrombotic events as well as thromboembolism), history of clinically significant hypercoagulability, or family history of hypercoagulability. 

16. Any prior history of or current documented atrial fibrillation episode, regardless of if paroxysmal or asymptomatic. 

17. Clinically significant bleeding diathesis, or on an anticoagulant therapy. 

18. Biopsy-proven or clinically-suspected inflammatory bowel disease (eg, 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). 

19. History of GI perforation or abscess. 

20. History of or clinically suspected SLE. 

21. Pre-existing demyelinating disorder such as multiple sclerosis. 

22. History of new onset seizures, unexplained sensory, motor, or cognitive, behavioral, or neurological deficits within the last 12 months before screening. 

23. Any major illness/condition or evidence of an unstable clinical condition at screening or baseline including, but not limited to, renal, hepatic, hematologic, GI, endocrine, cardiac, pulmonary, immunologic, rheumatologic, or infection (including pulmonary infection), that, in the investigator’s judgment, will substantially increase the risk to the participant, or confound the interpretation of safety assessments, if they were to participate in the study.

24. Cancer or history of cancer or lymphoproliferative disease within the previous 5 years (other than resected cutaneous basal cell or squamous cell carcinoma that has been treated with no evidence of recurrence) and under current treatment for cancer or lymphoproliferative disease.

25. Any history of acute coronary syndrome (myocardial infarction, unstable angina pectoris, or need for urgent coronary revascularization) or cerebrovascular event within 5 years before screening.

26. COVID-19 infection requiring hospitalization within 90 days before baseline (Day 1)or mild COVID-19 infection within 30 days before baseline.

27. Persistent symptoms or sequelae following COVID-19 infection, such as Long COVID.

28. Any vaccination within 30 days before baseline (Day 1). 

29. Pregnant or lactating. 

30. Any major surgery (eg, requiring general anesthesia or would lead to significant recovery time that would impede participation in the clinical trial or confound the interpretation of the safety results) scheduled or expected during the study. 

31. Any ocular surgery (regardless of need for general anesthesia or significant recovery time) scheduled or expected during the study, such as cataract, laser peripheral iridotomy, refractive, or retinal detachment surgery. 

32. Any prior history of or current serious psychiatric disorder or alcohol/drug abuse that, in the opinion of the investigator, may impact the assessment of safety, efficacy, or protocol adherence. 

33. Any other condition that, in the opinion of the investigator, would impair the ability of the participant to comply with the study procedures or impair the ability to interpret data from the participant’s participation in the study (eg, including uveitis, macular degeneration, optic nerve disease). 

Prior/Concomitant Therapy

34. History of systemic (eg, oral or IV) steroid use with a cumulative dose equivalent to >1 g of methylprednisolone for the treatment of TED. Previous oral steroid use with a cumulative dose of ≤1 g methylprednisolone (or equivalent dosage for other systemic corticosteroid) for the treatment of TED, however, is allowed if the corticosteroid was discontinued at least 6 weeks before baseline (Day 1) and completely tapered by baseline (if applicable). 

35. Systemic (eg, oral or IV) corticosteroid use for conditions other than TED within 6 weeks of baseline (Day 1) or not completely tapered by baseline (if applicable). Topical steroids for dermatological conditions, however, are allowed. Inhaled steroids are also permitted as long as no systemic effects are observed or anticipated per investigator’s opinion. 

36. Eye drops with corticosteroids or other anti-inflammatory activity (eg, cyclosporine eye drops) or vasoconstrictor activity. Previous use of eye drops with corticosteroids (or other anti-inflammatory activity) or vasoconstrictor activity, however, is allowed if these eye drops were discontinued at least 4 weeks before screening. In addition, the use of other topical eye treatments as supportive care (eg, artificial tears without added vasoconstrictors, or non-steroidal eye drops, gels or ointments) in accordance with standard of care, however, are permitted. 

37. Selenium supplements and biotin supplements must be discontinued 3 weeks before baseline (Day 1) and must not be restarted during the trial. However, taking a multivitamin is allowed. 

38. Any previous treatment with teprotumumab or other agent that inhibits the IGF-1 receptor. 

39. Any previous treatment with rituximab or other agent that binds CD20. 

40. Any previous treatment with tocilizumab or other agent that inhibits IL-6R. 

41. Any previous treatment with an agent that inhibits IL-6. 

42. Any previous treatment with an immunomodulatory or immunosuppressive agent other than systemic corticosteroids within 5 half-lives of the drug or 12 weeks (whichever is longer) before baseline (Day 1). (For details on the exclusion criterion for prior treatment with systemic corticosteroids, please see exclusion criteria 34 and 35 above). 

43. Use of an investigational agent for any condition within 5 half-lives of the drug or 12 weeks (whichever is longer) before baseline (Day 1). 

44. Any planned or expected use over the duration of the study of a prohibited concomitant therapy (refer to Appendix 6 for the list of prohibited concomitant therapies). 

45. Any planned live (attenuated) vaccination during the course of this study. 

Prior/Concurrent Clinical Study Experience

46. Known hypersensitivity to any of the components of TOUR006 or prior hypersensitivity reactions to mAb or other Fc-bearing protein. 

47. Known prior exposure to this investigational agent (TOUR006 or also known previously as PF-04236921). 

Diagnostic Assessments

48. Abnormality in any of the following testing assessments at screening as outlined below: 

• Positive human immunodeficiency virus test; 
• Positive hepatitis B virus test that is consistent with current or prior infection (note: positive hepatitis B surface antibody test consistent with prior vaccination but no infection is not an exclusion criterion); 
• Positive hepatitis C virus test; 
• Positive QuantiFERON Gold TB test 
• Alanine aminotransferase or aspartate aminotransferase levels ≥1.5 × ULN; 
• Total bilirubin level ≥1.5 × ULN; 
• Hemoglobin level <10.0 g/dL; 
• Platelet count ≤100 × 109/L (100,000 cells/mm³) or ≥1000 x 109/L (1,000,000 cells/mm³); 
• White blood cell count ≤3.5 × 109/L (3500 cells/mm³); 
• ANC <2000 cells/mm³; 
• Serum creatinine level ≥177 μmol/L (2 mg/dL); 
• hemoglobin A1c ≥9.5% at screening 
• Fasting LDL-C ≥160 mg/dL 
• Uncontrolled hypertension, defined as a systolic value ≥160 mm Hg or diastolic value ≥100 mm Hg at screening, confirmed on 2 measures ≥30 minutes apart.