Expanded Access Protocol of Teprotumumab (HZN-001) for Patients With Active Thyroid Eye Disease
Expanded Access Protocol of Teprotumumab (HZN-001) for Patients With Active Thyroid Eye Disease
This is an expanded access protocol intended to provide access to teprotumumab for the
 treatment of up to 60 patients in the United States with active moderate to severe thyroid
 eye disease where there is no comparable or satisfactory alternative therapy for treatment.
Requests for access to the Sponsor must be made by a licensed physician for a specific
 patient, based on a determination with the patient that the benefits of treatment with the
 investigational drug outweigh the risks. Licensed physician's with eligible patients must
 apply and meet requirements for participation in the expanded access program.
Inclusion Criteria:

 1. Written informed consent.

 2. Male or female patient at least 18 years old.

 3. Clinical diagnosis active TED with a CAS ≥ 4 (on the 7-item scale).

 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 patient records) within approximately
 12 months prior to eligibility review.

 6. Patients 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 Eligibility review. Every effort
 should be made to correct the mild hypo- or hyperthyroidism promptly and to maintain
 the euthyroid state for the full duration of participation.

 7. Does not require immediate surgical ophthalmological intervention.

 8. Diabetic patients must have well-controlled stable disease (defined as HbA1c < 9.0%).

 9. Women of childbearing potential (including those with an onset of menopause <2 years,
 non-therapy-induced amenorrhea for <12 months, or not surgically sterile [absence of
 ovaries and/or uterus]) must have a negative serum pregnancy test within 3 weeks prior
 to the first infusion and negative urine pregnancy tests at all protocol-specified
 timepoints (i.e., prior to each infusion); patients who are sexually active with a
 non-vasectomized male partner must agree to use 2 reliable forms of contraception
 during the expanded access program, 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 the first infusion and continue for 180 days after the last dose of
 investigational 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, some intrauterine devices (IUDs), sexual
 abstinence or vasectomized partner.

 10. Male patients must be surgically sterile or, if sexually active with a female partner
 of childbearing potential, must agree to use a barrier contraceptive method from the
 first infusion through 180 days after the last dose of investigational drug.

 11. Patient is willing and able to comply with the prescribed treatment protocol and
 evaluations for the duration of their participation.

 Exclusion Criteria:

 1. Any treatment with rituximab (Rituxan® or MabThera®) within 12 months prior to the
 first infusion of teprotumumab or tocilizumab (Actemra® or Roactemra®) within 6 months
 prior to the first infusion of teprotumumab. Use of any other non-steroid
 immunosuppressive agent within 3 months prior to the first infusion of teprotumumab.

 2. Use of an investigational agent for any condition within 60 days prior to the first
 infusion or anticipated use during the course of the protocol.

 3. Pregnant or lactating women.

 4. Biopsy-proven or clinically suspected IBD (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).

 5. Known hypersensitivity to any of the components of teprotumumab or prior
 hypersensitivity reactions to mAbs.

 6. Any other condition that, in the opinion of the Sponsor, would preclude inclusion in
 the expanded access program.

 7. Previous enrollment in this study or participation in a prior teprotumumab clinical
 study.

 8. Human immunodeficiency virus, hepatitis C or hepatitis B infections.