| Eligibility |
Inclusion Criteria:
1. Written informed consent.
2. Male or female between the ages of 18 and 80 years, inclusive, at Screening.
3. Meets the 2013 American College of Rheumatology/European League Against Rheumatism
classification criteria for systemic sclerosis (SSc) with a total score of =9.
4. Classified as having skin involvement proximal to elbow, knee, face and neck.
5. At the time of enrollment, no more than 60 months must have elapsed since the onset of
the first dcSSc manifestations, other than Raynaud's phenomenon.
6. Skin thickening from dcSSc in the forearm suitable for repeat biopsy.
7. Modified Rodman Skin Score (mRSS) units =10 and =45 at Screening.
8. Participant will be allowed to take CellCept® (mycophenolate mofetil) up to 3 g/day or
Myfortic® (mycophenolic acid) up to 2.14 g/day and low-dose prednisone (=10 mg/day or
equivalent dosing of glucocorticoids). Participants taking CellCept or Myfortic have
been doing so for =20 weeks and the dose must have been stable for =16 weeks prior to
the Day 1 Visit. Prednisone must have been at a stable dose for =4 weeks prior to the
Day 1 Visit.
9. Diabetic participants must have glycated hemoglobin (HbA1c) =8.0%, 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, nontherapy-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 throughout the
participant's participation in 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 <1% per year), when used
consistently and correctly, include implants, injectables, combined oral
contraceptives, some intrauterine devices, sexual abstinence or vasectomized partner.
11. Willing and able to comply with the prescribed treatment protocol and evaluations for
the duration of the study.
Exclusion Criteria:
1. Diagnosed with limited cutaneous SSc or sine scleroderma.
2. Diagnosed with other autoimmune connective tissue diseases, except for fibromyalgia,
scleroderma associated myopathy and Sjogren's syndrome.
3. Scleroderma renal crisis diagnosed within 6 months of the Screening Visit,
characterized by abrupt onset of hypertension and acute kidney injury.
4. Forced vital capacity (FVC) <50% predicted, diffusing capacity of the lungs for carbon
monoxide (DLCO) <40% predicted or pulmonary arterial hypertension (PAH) by right heart
catheterization requiring treatment with more than one oral PAH approved therapy or
parenteral therapy (intermittent use of phosphodiesterase-5 inhibitors are allowed for
erectile dysfunction and/or Raynaud's phenomenon/digital ulcers).
5. Corticosteroid use for conditions other than dcSSc within 4 weeks prior to Screening
(topical steroids for dermatological conditions and inhaled steroids are allowed).
6. Previous treatment with rituximab (Rituxan® or MabThera®) within 12 months prior to
the first infusion.
7. Use of a non-steroidal immunosuppressive agent, cytotoxic or anti-fibrotic drug within
4 weeks of Screening, including cyclophosphamide, azathioprine (Imuran®), methotrexate
or other immunosuppressive or cytotoxic medication. Exceptions are mycophenolate
mofetil (CellCept) and mycophenolic acid (Myfortic), which are permitted according to
inclusion criterion 8, and anti-malarials (e.g., hydroxychloroquine [Plaquenil®]).
8. Use of biologics or small molecules approved for rheumatoid arthritis, psoriatic
arthritis and other rheumatic diseases within 4 weeks prior to Screening.
9. Use of an investigational agent for any condition within 90 days or 5 half-lives,
whichever is longer, prior to Screening or anticipated use during the course of the
trial.
10. Malignant condition in the past 5 years (except successfully treated basal/squamous
cell carcinoma of the skin or cervical cancer in situ).
11. Pregnant or lactating women.
12. 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.
13. 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).
14. Known hypersensitivity to any of the components of TEPEZZA or prior hypersensitivity
reactions to mAbs.
15. Previous enrollment in this study or participation in a prior teprotumumab-trbw
clinical trial.
16. Human immunodeficiency virus, untreated or positive viral load for hepatitis C or
hepatitis B infections.
17. Previous organ transplant (including allogeneic and autologous marrow transplant).
18. Alanine aminotransferase or aspartate aminotransferase >2.5 times the upper limit of
normal or estimated glomerular filtration rate of <30 mL/min/1.73m^2 at Screening.
19. Platelets <100×10^3/µL.
20. Hemoglobin <8 g/dL.
21. Any other condition that, in the opinion of the Investigator, would preclude inclusion
in the study.
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