An Open-label Study (OLE) for Non-responders of VRDN-001-101 and VRDN-001-301

Viridian Therapeutics, Inc.139 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

139

Conditions

Thyroid Eye Disease

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (45)

Advancing Research International, LLC

Los Angeles, California, United States

USC Eye Institute

Los Angeles, California, United States

Advancing Research International, LLC

Newport Beach, California, United States

Stanford Byers Eye Institute

Palo Alto, California, United States

Cockerham Eye Consultants, PC

San Diego, California, United States

Outcomes

Primary Outcomes

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 not imputed.

Time frame: Baseline to Week 15

Secondary Outcomes

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 not imputed.

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 not imputed.

Time frame: Baseline to Week 15

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 not imputed.

Time frame: Baseline, Week 15

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 not imputed.

Time frame: Week 15

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 not imputed.

Time frame: Baseline to Week 15

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 not imputed.

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 not imputed.

Time frame: Week 15