Thyroid Eye Disease
Conditions
Keywords
Thyroid Eye Disease, Thyroid-Associated Ophthalmopathy, Dysthyroid Ophthalmopathy, Graves Eye Disease, Graves Orbitopathy, Myopathic Ophthalmopathy, Congestive Ophthalmopathy, Edematous Ophthalmopathy, Infiltrative Ophthalmopathy, TED, Thyroid-Associated Orbitopathy, Graves Disease
Brief summary
This is a clinical trial assessing the efficacy, safety, and tolerability of an investigational drug, veligrotug (VRDN-001), in participants with chronic thyroid eye disease (TED).
Detailed description
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.
Interventions
DRUGVeligrotug
5 IV Infusions of veligrotug 10 mg/kg
DRUGPlacebo
5 IV Infusions of veligrotug matched placebo
Sponsors
Viridian Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Must have moderate to severe chronic TED with documented evidence of ocular symptoms or signs that began greater than 15 months prior to screening * Must have had a clinical diagnosis of TED, with any CAS (0-7) * 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
* Must not have received prior treatment with another anti-IGF-1R therapy * Must not have received systemic corticosteroids for any condition, including TED, or selenium within 2 weeks prior to first dose * Must not have received other immunosuppressive drugs or another investigational agent for any condition, including TED, or any other therapy for TED, within 8 weeks prior to first dose * Must not have received radioactive iodine (RAI) treatment within 8 weeks prior to first dose * Must not have a pre-existing ophthalmic condition in the study eye that in the opinion of the study doctor would confound interpretation of the study results * Must not have had previous orbital irradiation or decompression surgery for TED to the study eye's orbit * Must not have inflammatory bowel disease * Must not have abnormal baseline audiometry Pure Tone Average (PTA) assessment or history of significant (as determined by the Investigator) ear pathology, relevant ear surgery or hearing loss. * Female TED participants must not be pregnant or lactating
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proptosis Responder Rate (PRR) in the Most Proptotic Eye as Measured by Exophthalmometer | Baseline to Week 15 | 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
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Proptosis in the Most Proptotic Eye as Measured by Exophthalmometer | Baseline, Week 15 | 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. |
| PRR in the Most Proptotic Eye, as Measured by Magnetic Resonance Imaging (MRI)/Computed Tomography (CT) | Baseline to Week 15 | 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. |
| Change From Baseline in Proptosis in the Most Proptotic Eye as Measured by MRI/CT | Baseline, Week 15 | 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. |
| Clinical Activity Responder Rate in the Most Proptotic Eye as Measured by Exophthalmometer | Week 15 | 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. |
| Overall Responder Rate (ORR) Comprising PRR and Clinical Activity Responder Rate in the Most Proptotic Eye as Measured by Exophthalmometer | Baseline to Week 15 | 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. |
| Diplopia Responder Rate | Week 15 | 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. |
| Diplopia Resolution Rate | Week 15 | 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. |
Countries
Australia, France, Germany, Hungary, Poland, Spain, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 50.7 years STANDARD_DEVIATION 12.03 |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 15 Participants |
| Race/Ethnicity, Customized Ethnicity Missing | 1 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 46 Participants |
| Race/Ethnicity, Customized Ethnicity Not Reported | 10 Participants |
| Race/Ethnicity, Customized Ethnicity Unknown | 2 Participants |
| Race/Ethnicity, Customized Race Asian | 3 Participants |
| Race/Ethnicity, Customized Race Black or African American | 19 Participants |
| Race/Ethnicity, Customized Race Missing | 5 Participants |
| Race/Ethnicity, Customized Race Multiple | 2 Participants |
| Race/Ethnicity, Customized Race Not Reported | 6 Participants |
| Race/Ethnicity, Customized Race Other | 5 Participants |
| Race/Ethnicity, Customized Race Unknown | 0 Participants |
| Race/Ethnicity, Customized Race White | 94 Participants |
| Sex: Female, Male Female | 95 Participants |
| Sex: Female, Male Male | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 125 | 0 / 63 |
| other Total, other adverse events | 87 / 125 | 22 / 63 |
| serious Total, serious adverse events | 10 / 125 | 3 / 63 |
Outcome results
None listed