An Efficacy, Safety, and Tolerability Study of Veligrotug (VRDN-001), in Participants With Chronic Thyroid Eye Disease (TED)

This is a randomized (meaning participants will be assigned to study arms by chance), double-masked (meaning study doctor and participant will not know which study arm participant is assigned to), placebo-controlled study that will include participants with chronic TED. The key objectives of this study are to determine if veligrotug (VRDN-001) is efficacious, safe, and tolerable when administered as 5 IV infusions given every 3 weeks for a total of 12 weeks in participants with chronic TED.

Primary Outcome Measures

1. Proptosis Responder Rate (PRR) in the Most Proptotic Eye as Measured by Exophthalmometer
   Proptosis response in the most proptotic eye was defined as a reduction of proptosis of ≥2 millimeters (mm) from baseline in the most proptotic eye (without a corresponding increase of ≥2 mm in the other eye) as measured by exophthalmometer. Missing data were imputed with the Multiple Imputation (MI) method.

Secondary Outcome Measures

1. Change From Baseline in Proptosis in the Most Proptotic Eye as Measured by Exophthalmometer
   Proptosis was defined as distance between the lateral orbital rim and the most anterior position of the cornea in mm, measured using an exophthalmometer. Missing data were imputed with the MI method.
2. PRR in the Most Proptotic Eye, as Measured by Magnetic Resonance Imaging (MRI)/Computed Tomography (CT)
   Proptosis responder in the most proptotic eye by MRI/CT was defined as a reduction of proptosis of ≥2 mm from baseline in the most proptotic eye by MRI/CT (without a corresponding increase of ≥2 mm in the other eye) as measured by MRI/CT. Missing data were imputed using the Exophthalmometer Imputation (EXI) method, as applicable.
3. Change From Baseline in Proptosis in the Most Proptotic Eye as Measured by MRI/CT
   Measurement of proptosis was conducted by the central imaging reading center using MRI/CT of the orbits acquired without contrast. Measurements were conducted by 2 independent readers with adjudication if the difference between the 2 primary readers in proptosis measurement exceeded 5% (calculated as the difference divided by the larger measurement). The average of 2 (or 3 if adjudicated) measurements were used for analyses. Missing data were imputed using the EXI method, as applicable.
4. Clinical Activity Responder Rate in the Most Proptotic Eye as Measured by Exophthalmometer
   Clinical activity responder in the most proptotic eye was defined as no worsening in clinical activity score (CAS) from baseline in the most proptotic eye without a corresponding increase of ≥2 points in the other eye. Missing data were imputed with the MI method.
5. Overall Responder Rate (ORR) Comprising PRR and Clinical Activity Responder Rate in the Most Proptotic Eye as Measured by Exophthalmometer
   ORR was comprised of PRR in the most proptotic eye (reduction of proptosis of ≥2 mm from baseline in the most proptotic eye \[without a corresponding increase of ≥2 mm in the other eye\]) as measured by exophthalmometer at Week 15 and Clinical Activity Responder rate in the most proptotic eye (no worsening in CAS from baseline in the most proptotic eye without a corresponding increase of ≥2 points in the other eye) as measured by exophthalmometer at Week 15. Missing data were imputed with the MI method.
6. Diplopia Responder Rate
   A diplopia responder was defined as having a decrease of ≥1 from baseline for participants with a baseline Gorman subjective diplopia score \>0. Gorman subjective diplopia score (range, 0 to 3) includes 4 categories: no diplopia (absent, scored as 0), diplopia in the primary position of gaze when the participant is tired or awakening (intermittent, scored as 1), diplopia at extremes of gaze (inconstant, scored as 2), and continuous diplopia in the primary or reading position (constant, scored as 3). Missing data were imputed with the MI method.
7. Diplopia Resolution Rate
   Diplopia resolution was defined as reduction in Gorman subjective diplopia score to 0 from baseline for participants with baseline Gorman subjective diplopia score \>0. Gorman subjective diplopia score (range, 0 to 3) includes 4 categories: no diplopia (absent, scored as 0), diplopia in the primary position of gaze when the participant is tired or awakening (intermittent, scored as 1), diplopia at extremes of gaze (inconstant, scored as 2), and continuous diplopia in the primary or reading position (constant, scored as 3). Missing data were imputed with the MI method.