Trial Outcomes & Findings for A Safety, Tolerability, and Efficacy Study of Veligrotug (VRDN 001) in Participants With Thyroid Eye Disease (TED) (NCT NCT05176639)

As prespecified, data were collected and reported for the participants. Therefore, the 'Ns' reported below = number of participants analyzed regardless of which eye was evaluated. The primary and secondary efficacy analyses and safety analysis were measured in the pre-specified study eye per individual participant.

Ocular assessments were performed in both eyes at baseline. Study eye was the most proptotic eye by exophthalmometer at baseline. If both eyes were equally proptotic, then the eye with the worse visual acuity (VA) was designated as the study eye. If proptosis and VA were equal in both eyes, then the right eye was designated as the study eye.

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

Proptosis responder in the study eye was defined as a reduction of proptosis of ≥2 millimeters (mm) from baseline in the study eye (without a corresponding increase of ≥2 mm in the fellow eye) as measured by exophthalmometer. Missing data were imputed with the Multiple Imputation method.

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 Multiple Imputation method.

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 method, as applicable.

Measurement of proptosis 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 Exophthalmometer Imputation method, as applicable.

The CAS was based on 7 components: spontaneous retrobulbar pain, pain on attempted eye movements (upward, side to-side, and downward gazes), conjunctival redness, redness of the eyelids, chemosis, swelling of the caruncle or plica and swelling of the eyelids. Each component was scored as present or absent (scored as 1 or 0, respectively), and the CAS was given as the sum of the scores (range, 0 to 7, with higher scores indicating greater level of inflammation). Missing data were imputed with the Multiple Imputation method.

ORR in the study eye was comprised of PRR in the study eye (reduction of proptosis of ≥ 2 mm from baseline \[without a corresponding increase of ≥ 2 mm in the fellow eye\]) and clinical activity responder in the study eye (reduction in clinical activity score \[CAS\] ≥ 2 points from baseline \[without a corresponding increase of ≥ 2 points in the fellow eye\]). CAS ranged from 0 to 7, with higher scores indicating greater level of inflammation. Proptosis (distance between the lateral orbital rim and the most anterior position of the cornea in mm) was measured using an exophthalmometer. Missing data were imputed with Multiple Imputation method.

Clinical activity responder rate in the study eye was defined as a reduction in CAS ≥2 points from baseline in the study eye (without a corresponding increase of ≥2 points in the fellow eye). Missing data were imputed with the Multiple Imputation method.

Diplopia responder was defined as reduction in Gorman subjective diplopia score of ≥1 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 Multiple Imputation method.

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 Multiple Imputation method.

The CAS was based on 7 components: spontaneous retrobulbar pain, pain on attempted eye movements (upward, side to-side, and downward gazes), conjunctival redness, redness of the eyelids, chemosis, swelling of the caruncle or plica and swelling of the eyelids. Each component was scored as present or absent (scored as 1 or 0, respectively), and the CAS was given as the sum of the scores (range, 0 to 7, with higher scores indicating greater level of inflammation). Missing data were imputed with the Multiple Imputation method.