Two Proposed Randomized Placebo-Controlled Clinical Studies Assessing Subcutaneous Administration of VRDN-003, a Next-Generation Full Antagonist Antibody to IGF-1R, in Patients With Thyroid Eye Disease (TED), REVEAL-1 and REVEAL-2
Author: Antonio Manuel Garrido Hermosilla
Base Hospital / Institution: Andalusian Referral Unit for Thyroid Eye Disease (Andalusian Public Health System), Oculoplastics-Orbit and Ocular Oncology Units, Department of Ophthalmology, Virgen Macarena University Hospital, Seville, Spain; Associate Professor of Ophthalmology, Department of Surgery, Faculty of Medicine, University of Seville, Seville, Spain
ePoster presentation
Abstract ID: 24-217
Purpose
VRDN-001 and VRDN-003 are full antagonist antibodies to the IGF-1 receptor (IGF-1R). These antibodies have the same binding domain, but VRDN-003 contains half-life extension modifications. Prior phase 2 proof-of-concept data for VRDN-001 showed clinically meaningful improvements in thyroid eye disease (TED) signs and symptoms after 2 intravenous (IV) infusions administered every 3 weeks (Q3W). Phase 1 data for VRDN-003 in healthy volunteers showed that its half-life is 4-5 times that of VRDN-001, potentially enabling low-volume subcutaneous dosing as infrequently as Q8W, while achieving exposures in the range of those observed with VRDN-001 IV dosing Q3W. The safety and efficacy of subcutaneous administration of VRDN-003 are planned to be evaluated in 2 randomized placebo-controlled clinical studies in patients with moderate-to-severe active TED (REVEAL-1) and chronic TED (REVEAL-2).
Methods
The planned studies aim to evaluate VRDN-003 vs placebo administered as a subcutaneous injection in at least 1 of 3 dosing regimens: Q2W, Q4W, and Q8W. For REVEAL-1, patients must have a clinical activity score (CAS) of ≥3 and onset of signs/symptoms within 15 months of enrollment; for REVEAL-2, patients can have any CAS and must have onset of signs/symptoms at least 15 months prior to enrollment.
Results
Efficacy assessments will include measures of proptosis, diplopia, CAS, eyelid retraction, and quality of life. Safety and tolerability will be assessed through the full study period. Patients who are nonresponders at the end of the treatment phase will have the option to receive a full course of one of the treatment regimens of VRDN-003.
Conclusion
VRDN-003 is in development as a SC treatment for TED with the goal of reducing the treatment burden currently associated with IV infusions. The REVEAL-1 and REVEAL-2 randomized, double-masked, placebo-controlled trials will be the first to assess VRDN-003 SC in patients with TED.
Additional Authors
| First name | Last name | Base Hospital / Institution |
|---|---|---|
| Thomas | Ciulla | Andalusian Referral Unit for Thyroid Eye Disease (Andalusian Public Health System), Oculoplastics-Orbit and Ocular Oncology Units, Department of Ophthalmology, Virgen Macarena University Hospital, Seville, Spain; Associate Professor of Ophthalmology, Department of Surgery, Faculty of Medicine, University of Seville, Seville, Spain |
| Abhijit | Narvekar | Andalusian Referral Unit for Thyroid Eye Disease (Andalusian Public Health System), Oculoplastics-Orbit and Ocular Oncology Units, Department of Ophthalmology, Virgen Macarena University Hospital, Seville, Spain; Associate Professor of Ophthalmology, Department of Surgery, Faculty of Medicine, University of Seville, Seville, Spain |
| Steven | Leibowitz | Andalusian Referral Unit for Thyroid Eye Disease (Andalusian Public Health System), Oculoplastics-Orbit and Ocular Oncology Units, Department of Ophthalmology, Virgen Macarena University Hospital, Seville, Spain; Associate Professor of Ophthalmology, Department of Surgery, Faculty of Medicine, University of Seville, Seville, Spain |
