Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Multicenter, Double-Masked, Placebo-Controlled, Efficacy And Safety Study Of RV 001, An Insulin-Like Growth Factor-1 Receptor (IGF-1R) Antagonist Antibody (Fully Human), Administered Every 3 Weeks (q3W) By Intravenous (IV) Infusion In Patients Suffering From Active Thyroid Eye Disease (TED)
Brief Summary: The primary objective of this study is to investigate the efficacy, safety, and tolerability of RV 001 (teprotumumab), a fully human anti-IGF1R antibody, administered q3W for 6 months, in comparison to placebo, in the treatment of participants suffering from active TED.

"Funding Source - FDA OOPD"


Options:
A: Inclusion Criteria:

* Patients with clinical activity score (CAS) of ≥4 and moderate to severe disease severity, as defined by thyroid eye disease severity scale based on the first letter of the defining characteristic of each class, the classification is known as: 'no signs or symptoms; only signs; soft tissue; proptosis; extraocular muscle; cornea; sight loss' (NOSPECS) score
* Euthyroid for at least 6-8 weeks
* No immediate need for decompression surgery
* With disease progression over the previous 1-2 months or without evident improvement in the prior 6 months.

Exclusion Criteria:

* Corticosteroid use in the preceding 4 weeks
* HIV, hepatitis C or hepatitis B infections
* Denied consent for HIV or hepatitis testing
* Mild or inactive Graves' ophthalmopathy
* Orbital radiotherapy within 18 months or orbital surgery within the past year
* Absolute neutrophil count \< 1,500/mm\^3
* Pregnant or nursing patients
* Coronary artery disease, congestive heart failure, significant arrhythmias, significant infection or immunodeficiency, other serious illnesses
B: Inclusion Criteria:

1. Written informed consent.
2. Male or female participant between the ages of 18 and 80 years, inclusive, at Screening.
3. Clinical diagnosis of Graves' disease associated with active TED with a Clinical Activity Score (CAS) ≥ 4 (on the 7-item scale) for the most severely affected eye at Screening and Baseline.
4. Moderate-to-severe active TED (not sight-threatening but has an appreciable impact on daily life), usually associated with one or more of the following: lid retraction ≥ 2 mm, moderate or severe soft tissue involvement, exophthalmos ≥ 3 mm above normal for race and gender, and/or inconstant or constant diplopia.
5. Onset of active TED symptoms (as determined by participant records) within 9 months prior to Baseline.
6. Participants must be euthyroid with the baseline disease under control or have mild hypo- or hyperthyroidism (defined as free thyroxine \[FT4\] and free triiodothyronine \[FT3\] levels \< 50% above or below the normal limits) at Screening. Every effort should be made to correct the mild hypo- or hyperthyroidism promptly and to maintain the euthyroid state for the full duration of the clinical trial.
7. Does not require immediate surgical ophthalmological intervention and is not planning corrective surgery/irradiation during the course of the study.
8. Alanine aminotransferase (ALT) or AST ≤ 3 times the upper limit of normal (ULN) or serum creatine \<1.5 times the ULN according to age at Screening.
9. Diabetic participants must have well-controlled stable disease (defined as HbA1C \< 9.0% with no new diabetic medication \[oral or insulin\] or more than a 10% change in the dose of a currently prescribed diabetic medication within 60 days prior to Screening).
10. Women of childbearing potential (including those with an onset of menopause \<2 years prior to Screening, non-therapy-induced amenorrhea for \<12 months prior to Screening, or not surgically sterile \[absence of ovaries and/or uterus\]) must have a negative serum pregnancy test at Screening and negative urine pregnancy tests at all protocol-specified timepoints (i.e., prior to each dose and through Week 48 of the Follow-Up Period); participants who are sexually active with a non-vasectomized male partner must agree to use 2 reliable forms of contraception during the trial, one of which is recommended to be hormonal, such as an oral contraceptive. Hormonal contraception must be started at least one full cycle prior to Baseline and continue for 180 days after the last dose of study drug. Highly effective contraceptive methods (with a failure rate less than 1% per year) when used consistently and correctly, includes implants, injectables, combined oral contraceptives, intrauterine devices (IUDs), sexual abstinence or vasectomized partner.
11. Male participants must be surgically sterile or, if sexually active with a female partner of childbearing potential, must agree to use barrier contraceptive method from Screening through 180 days after the last dose of study drug.
12. Participant is willing and able to comply with the study protocol and evaluations for the duration of the study.

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 study eye between Screening and Baseline.
4. Decrease in proptosis of ≥ 2 mm in the study eye between Screening and Baseline.
5. Previous orbital irradiation or surgery for TED.
6. Any steroid use (intravenous \[IV\] or oral) with a cumulative dose equivalent to ≥ 1 g of methylprednisolone for the treatment of TED. Previous steroid use (IV or oral) with a cumulative dose of \<1 g methylprednisolone or equivalent for the treatment of TED and previous use of steroid eye drops is allowed if the corticosteroid was discontinued at least 4 weeks prior to Screening.
7. Corticosteroid use for conditions other than TED within 4 weeks prior to Screening (topical steroids for dermatological conditions and inhaled steroids are allowed).
8. Selenium and biotin must be discontinued 3 weeks prior to Screening and must not be restarted during the clinical trial; however, taking a multivitamin that includes selenium and/or biotin is allowed.
9. Any previous treatment with rituximab or tocilizumab. Use of any other non-steroid immunosuppressive agent within 3 months prior to Screening.
10. Use of an investigational agent for any condition within 60 days prior to Screening or anticipated use during the course of the trial.
11. Identified pre-existing ophthalmic disease that, in the judgment of the Investigator, would preclude study participation or complicate interpretation of study results.
12. Bleeding diathesis that in the judgment of the Investigator would preclude inclusion in the clinical trial.
13. Malignant condition in the past 12 months (except successfully treated basal/squamous cell carcinoma of the skin).
14. Pregnant or lactating women.
15. Current drug or alcohol abuse, or history of either within the previous 2 years, in the opinion of the Investigator or as reported by the participant.
16. Biopsy-proven or clinically suspected inflammatory bowel disease.
17. Known hypersensitivity to any of the components of teprotumumab or prior hypersensitivity reactions to mAbs.
18. Any other condition that, in the opinion of the Investigator, would preclude inclusion in the study.
19. Previous enrollment in this study or participation in a prior teprotumumab clinical trial.
20. Human immunodeficiency virus (HIV), hepatitis C or hepatitis B infections.
C: Inclusion Criteria:

* Between the ages of 8 and 45 years
* Within 3 months of diagnosis of type 1 diabetes
* Have presence of at least one diabetes-related autoantibody
* Must have stimulated C-peptide levels of at least 0.2 pmol/ml measured during a mixed meal tolerance test (MMTT) within one month of randomization
* If female with reproductive potential, willing to avoid pregnancy and undergo pregnancy testing while participating in the study
* Have not received an immunization for at least one month
* Must be willing to comply with intensive diabetes management
* Must weigh at least 25 kg at study entry

Exclusion Criteria:

* Are immunodeficient or have clinically significant chronic lymphopenia
* Have an active infection or positive purified protein derivative (PPD) test result
* Currently pregnant or lactating; or anticipate becoming pregnant.
* Require chronic use of steroids
* Have current or past HIV, hepatitis B, or hepatitis C infection
* Have any complicating medical issues that interfere with study conduct or cause increased risk
* Have a history of malignancies
* Currently using non-insulin pharmaceuticals that effect glycemic control
* Currently participating in another type 1 diabetes treatment study
D: Inclusion Criteria:

* Clinical diagnosis of Graves' disease associated with active TED and a clinical activity score of ≥ 4
* Fewer than 9 months from onset of TED
* No previous medical or surgical treatment, excluding local supportive measures and oral steroids if the maximum cumulative dose is less than 1000 mg methylprednisolone or equivalent with at least 6 weeks between last administration of oral steroids and randomization
* 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)

Exclusion Criteria:

* Optic neuropathy
* Corneal decompensation unresponsive to medical management
* Oral or IV steroid treatment for any non-TED reason in the preceding 3 months
* Poorly controlled diabetes
* Platelets \< 100 x 10\^9/L
* Hemoglobin concentration \> 2 g/dL below the lower limit of normal

Answer: D