Phase 1/2 Clinical Study of VRDN-001, A Full Antagonist Antibody to the Insulin-Like Growth Factor-1 Receptor (IGF-1R), in Patients with Thyroid Eye Disease (TED) (P3-9.001)
Bibliographic record
Abstract
Objective: Report results from the first cohort of TED patients treated with 2 intravenous infusions of 10 mg/kg VRDN-001 from our phase 1/2 double-masked randomized clinical trial (NCT05176639). Background: IGF-1R antagonism can reduce TED-related inflammation and proptosis. We are evaluating VRDN-001, a full antagonist antibody to IGF-1R, in TED patients at doses of 3, 10, and 20 mg/kg. Design/Methods: Adults with active moderate-to-severe TED and clinical activity score (CAS) ≥4 were randomized to 2 intravenous infusions 3 weeks apart of either 10 mg/kg VRDN-001 or placebo (3:1). Safety, tolerability, and efficacy were assessed. Endpoints included overall responder rate (% of subjects with ≥2 mm reduction in proptosis and ≥2 points reduction in CAS), proptosis responder rate (% of subjects with ≥2 mm improvement), change from baseline in proptosis and CAS, proportion of subjects with CAS decrease to 0 or 1, and diplopia resolution. Results: Baseline characteristics were similar between VRDN-001 (n=6) and placebo (n=2). After 2 infusions, the overall responder rate was 83% (5/6; VRDN-001) vs. 0% (0/2; placebo). Proptosis responder rate was 83% (5/6; VRDN-001) vs. 50% (1/2; placebo). Proptosis decreased by 2.4 mm (VRDN-001) vs. 1.0 mm (placebo) and CAS decreased by 4.3 (VRDN-001) vs. 1.5 (placebo). CAS decreased to 0 or 1 for 83% (5/6; VRDN-001) vs. 0% (0/2; placebo). In patients presenting with diplopia, complete resolution occurred for 75% (3/4; VRDN-001) vs. 0% (0/1; placebo). One case of transient hearing impairment that resolved by next visit, with normal audiometry, was reported. No serious AEs, hyperglycemia, or infusion reactions occurred. Conclusions: Two infusions of 10 mg/kg VRDN-001 led to rapid, substantial improvement across all efficacy measures at 6 weeks in TED patients, surpassing 6-week results from prior RCTs of other anti-IGF-1R antibodies. Results from the additional 3 mg/kg and 20 mg/kg cohorts may extend these findings and define potential VRDN-001 treatment regimens. Disclosure: Dr. Moster has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Gensight . Dr. Moster has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Viridian. Dr. Moster has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Kilcoyne and Nesbitt. Dr. Douglas has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Horizon Therapeutics. Dr. Douglas has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon Therapeutics. Dr. Douglas has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Horizon Therapeutics. Dr. Cockerham has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Horizon Therapeutics. Dr. Cockerham has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Viridian Pharmaceuticals. Dr. Cockerham has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon therapeutics. Dr. Cockerham has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Horizon Therapeutics. Dr. Cockerham has received research support from Viridian Pharmaceuticals. Dr. Turbin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. The institution of Dr. Turbin has received research support from Viridian. Dr. Nijhawan has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for College of Physicians and Surgeons of Ontario. Dr. Nijhawan has received research support from Viridian Therapeutics. The institution of Dr. Schiffman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Schiffman has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for lAW FIRMS. Dr. Schiffman has received intellectual property interests from a discovery or technology relating to health care. Dr. Ugradar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Viridian Therapeutics. Dr. Ugradar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Valenza Bio. Dr. Oshaughnessy has received personal compensation for serving as an employee of viridian therapeutics. Dr. Oshaughnessy has stock in viridian therapeutics. Mrs. Summerfelt has received personal compensation for serving as an employee of Viridian Therapeutics. An immediate family member of Mrs. Summerfelt has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Viridian Therapeutics. Mrs. Summerfelt has stock in Viridian Therapeutics. Dr. She has received personal compensation for serving as an employee of Viridian Therapeutics. Dr. She has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Dianthus Therapeutics. Dr. She has stock in Viridian Therapeutics. Dr. Katz has received personal compensation for serving as an employee of Viridian Therapeutics. Dr. Katz has received stock or an ownership interest from Viridian Therapeutics.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".