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

Viridian Therapeutics, Inc.113 enrolled

Overview

The investigational drug, veligrotug (VRDN-001), is a monoclonal antibody that inhibits the activity of a cell surface receptor called insulin-like growth factor-1 receptor (IGF-1R). Inhibition of IGF-1R may help to reduce the inflammation and associated tissue swelling that occurs in participants with thyroid eye disease (TED). The primary objective of this clinical trial is to establish the safety, tolerability, and efficacy of veligrotug, and the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of veligrotug in active TED participants who received 10 milligrams (mg)/kilogram (kg).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

113

Conditions

Thyroid Eye Disease

Interventions

Veligrotug

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria for Active TED Participants (THRIVE): * Must have moderate to severe active TED with documented evidence of ocular symptoms or signs that began within 15 months prior to screening * Must have Clinical Activity Score (CAS) of ≥ 3 on the 7-item scale for the study eye * Must agree to use highly effective contraception as specified in the protocol * Female TED participants must have a negative serum pregnancy test at screening Key Exclusion Criteria for Active TED Participants (THRIVE): * Must not have received prior treatment with another anti-IGF-1R therapy or any investigational agent for TED * Must not have used systemic corticosteroids or selenium within 2 weeks prior to Day 1 * Must not have received rituximab, tocilizumab or other immunosuppressive agents or any other therapy for TED within 8 weeks prior to Day 1 * Must not have received an investigational agent for any condition within 8 weeks prior to Day 1 * Must not have a pre-existing ophthalmic condition in the study eye that in the opinion of the Investigator would confound interpretation of the study results * Must not have had previous orbital irradiation or surgery for TED in the study eye * Must not have a history of inflammatory bowel disease * Must not have a history of or screening audiometry assessment of clinically significant (as determined by investigator) ear pathology, relevant ear surgery, or hearing loss * Female TED participants must not be pregnant or lactating Note: Prior thyroidectomy, radioactive iodine (RAI) treatment, or orbital decompression surgery limited to bone only are NOT exclusions.

Locations (53)

University of Colorado - Department of Ophthalmology

Aurora, California, United States

The Private Office of Raymond Douglas

Beverly Hills, California, United States

USC Roski Eye Institute

Los Angeles, California, United States

MACRO Trials, Inc.

Los Angeles, California, United States

Amy Patel Jain, MD

Newport Beach, California, United States

Outcomes

Primary Outcomes

Proptosis Responder Rate (PRR) in the Study Eye As Measured by Exophthalmometer

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.

Time frame: Baseline to Week 15

Secondary Outcomes

Change From Baseline in Proptosis in the Study 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 Multiple Imputation method.

Time frame: Baseline, Week 15

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 method, as applicable.

Time frame: Week 15

Change From Baseline in Proptosis in the Most Proptotic Eye As Measured by MRI/CT

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.

Time frame: Baseline, Week 15

Change From Baseline in CAS in the Study Eye

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.

Time frame: Baseline, Week 15

Overall Responder Rate (ORR) Comprising of PRR and Clinical Activity Responder Rate in the Study Eye

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.

Time frame: Baseline to Week 15

Clinical Activity Responder Rate in the Study Eye

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.

Time frame: Week 15

Diplopia Responder Rate

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.

Time frame: Week 15

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 Multiple Imputation method.

Time frame: Week 15

Percentage of Participants With a CAS of 0 or 1 in the Study Eye

Time frame: Week 15