Thyroid Eye Disease
Conditions
Keywords
Graves Disease, Thyroid-Associated Ophthalmopathy, Thyroid Eye Disease, Dysthyroid Ophthalmopathy, Graves Eye Disease, Graves Orbitopathy, Myopathic Ophthalmopathy, Congestive Ophthalmopathy, Edematous Ophthalmopathy, Infiltrative Ophthalmopathy
Brief summary
The investigational drug, 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 objectives of this clinical trial are to provide open-label access to VRDN-001 for participants who were previously non-responders at 3 weeks post the fifth IV infusion (i.e., 15 weeks) in the VRDN-001-101 (THRIVE) and VRDN-001-301 (THRIVE-2) pivotal studies and assess the safety and efficacy of VRDN-001 in participants who were previously treated with VRDN-001 or placebo.
Interventions
DRUGVeligrotug
Veligrotug 10 mg/kg (5 infusions of Veligrotug 10 mg/kg)
Sponsors
Viridian Therapeutics, Inc.
Study design
Allocation
NA
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Be able to understand the study procedures and the risks involved and be willing to provide written informed consent before the first study-related activity 2. Have completed at least 5 IV infusions and assessments required to determine proptosis responder status 3 weeks post the fifth IV infusion (i.e., Week 15) as defined in either the VRDN-001-101 or VRDN-001-301 pivotal studies 3. Been a participant in either the VRDN-001-101 or VRDN-001-301 studies and found to be a non-responder as defined within the VRDN-001-101 or VRDN-001-301 study 4. Not require immediate surgical ophthalmological or orbital surgery in the study eye for any reason 5. Must agree to use highly effective contraception as specified in the protocol 6. Female TED participants must have a negative urine pregnancy test at screening 7. Be willing and able to comply with all the requirements of the protocol for the entire duration of the study Key
Exclusion criteria
Participants must not: 1. Have received prior treatment with another anti-IGF-1R agent 2. Have received systemic corticosteroids for any condition, including TED, or selenium within 2 weeks prior to first dose 3. Have received other immunosuppressive drugs or another investigational agent for any condition, including TED (other than VRDN-001 or placebo associated with the VRDN-001-101 or VRDN-001-301 pivotal studies), or any other therapy for TED, within 8 weeks prior to first dose 4. Have received radioactive iodine (RAI) treatment within 8 weeks prior to first dose 5. Have had previous orbital irradiation or decompression surgery involving excision of fat for TED to the study eye's orbit 6. Have abnormal hearing test before first dose. Have a history of ear conditions considered significant by study doctor
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 not imputed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 not imputed. |
| 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 not imputed. |
| 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 not imputed. |
| 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 not imputed. |
| 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 not imputed. |
| 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 not imputed. |
| 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 not imputed. |
Countries
France, Germany, Netherlands, 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. The study eye for the purpose of determining eligibility remained the same as that identified at baseline (last assessment performed prior to the Day 1 IV infusion) in the THRIVE (NCT05176639) or THRIVE-2 (NCT06021054) study.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 46.2 years STANDARD_DEVIATION 13.17 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 62 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants |
| Race/Ethnicity, Customized Race Asian | 9 Participants |
| Race/Ethnicity, Customized Race Black or African American | 11 Participants |
| Race/Ethnicity, Customized Race Not Reported | 4 Participants |
| Race/Ethnicity, Customized Race Other | 6 Participants |
| Race/Ethnicity, Customized Race Unknown | 1 Participants |
| Race/Ethnicity, Customized Race White | 105 Participants |
| Sex: Female, Male Female | 103 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 57 | 0 / 82 |
| other Total, other adverse events | 47 / 57 | 67 / 82 |
| serious Total, serious adverse events | 0 / 57 | 1 / 82 |
Outcome results
None listed