LAUSR

OBJECTIVES In Graves' disease (GD), autoantibodies to the thyroid stimulating hormone receptor (TSHR) cause hyperthyroidism. The condition is often associated with eye signs including proptosis, oedema, and diplopia (collectively termed Graves' orbitopathy (GO)). The safety profile of K1-70TM (a human monoclonal TSHR specific autoantibody, which blocks ligand binding and stimulation of the receptor) in patients with GD was evaluated in a phase I clinical trial. PATIENTS AND STUDY DESIGN Eighteen GD patients stable on anti-thyroid drug (ATD) medication received a single intramuscular (IM) or intravenous (IV) dose of K1-70TM during an open label phase I ascending dose, safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) study. Immunogenic effects of K1-70TM were also determined. RESULTS K1-70TM was well-tolerated in all subjects at all doses and no significant immunogenic response was observed. There were no deaths or serious adverse events. Increased systemic exposure to K1-70TM was observed following a change to IV dosing, indicating this was the correct dosage route. Expected PD effects occurred after a single IM dose of 25mg or single IV dose of 50mg or 150mg with fT3, fT4 and TSH levels progressing into hypothyroid ranges. There were also clinically significant improvements in symptoms of both GD (reduced tremor, improved sleep, improved mental focus, reduced toilet urgency) and GO (reduced exophthalmos measurements, reduced photosensitivity). This article is protected by copyright. All rights reserved.