VRDN-001 for Thyroid Eye Disease

(THRIVE Trial)

No longer recruiting at 106 trial locations

Overseen By Kimberly Cockerham

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Viridian Therapeutics, Inc.

Must not be taking: Corticosteroids, Rituximab, Tocilizumab, others

Disqualifiers: Diabetes, Renal impairment, Inflammatory bowel, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks for TED MAD participants, 15 weeks for Phase 3 participants

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, veligrotug (VRDN-001), for individuals with thyroid eye disease (TED), which causes eye swelling and irritation. The drug aims to block a protein that may reduce TED-related inflammation and swelling. Participants will receive either the drug or a placebo to assess its safety and effectiveness. The trial seeks individuals with moderate to severe TED symptoms that began within the last 15 months. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to a potentially groundbreaking treatment for TED.

Will I have to stop taking my current medications?

The trial requires that you stop using systemic corticosteroids at least 2 to 4 weeks before starting, and you must not have taken rituximab, tocilizumab, or other immunosuppressive agents within 8 to 12 weeks prior. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

Is there any evidence suggesting that veligrotug (VRDN-001) is likely to be safe for humans?

Research has shown that veligrotug (VRDN-001) has undergone testing in people. In earlier studies, most participants tolerated it well, experiencing only mild side effects such as headaches or slight skin reactions. For individuals with thyroid eye disease, the treatment reduced swelling and inflammation, which are primary symptoms of the condition. Importantly, no serious side effects were directly linked to VRDN-001. As the treatment remains under study, safety information is updated regularly. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for thyroid eye disease?

Unlike the standard treatments for Thyroid Eye Disease, which often include corticosteroids and surgery, VRDN-001 offers a novel approach by using an active ingredient called veligrotug. This drug works by targeting and blocking the insulin-like growth factor-1 receptor (IGF-1R), which is believed to play a key role in the inflammation and swelling associated with the disease. Researchers are excited about VRDN-001 because it has the potential to reduce symptoms more effectively and with fewer side effects compared to current options. Plus, the targeted mechanism of action could lead to faster relief for patients suffering from this condition.

What evidence suggests that VRDN-001 might be an effective treatment for thyroid eye disease?

Research has shown that veligrotug (VRDN-001) targets a specific part of the body involved in inflammation and swelling in thyroid eye disease (TED). In one study, 70% of patients who responded to the treatment experienced lasting improvement in their eye symptoms, even a year later. This finding suggests that VRDN-001 can effectively reduce TED symptoms. In this trial, participants will be randomized to receive either veligrotug (VRDN-001) or a placebo. The treatment aims to be a strong option for managing TED symptoms, offering long-term relief. Overall, the evidence is promising for those considering this treatment for thyroid eye disease. ^{2 5 6 7 8}

Who Is on the Research Team?

Thomas Ciulla, MD, MBA

Principal Investigator

Viridian Therapeutics, Inc.

Are You a Good Fit for This Trial?

This trial is for healthy individuals and those with Thyroid Eye Disease (TED), specifically moderate to severe cases. Participants should not have certain medical conditions like diabetes, recent kidney issues, or hearing loss. They must not have used specific medications recently and agree to use effective contraception.

Inclusion Criteria

I am not able to become pregnant.

Must agree to use highly effective contraception as specified in the protocol

Your eye condition must be rated as at least a 3 on a 7-point scale for the study.

Exclusion Criteria

I have never been treated with anti-IGF-1R monoclonal antibody.

I haven't taken rituximab, tocilizumab, or similar drugs in the last 8 weeks.

I haven't taken oral steroids in the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive two intravenous infusions of veligrotug (VRDN-001) or placebo

6 weeks for TED MAD participants, 15 weeks for Phase 3 participants

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• VRDN-001

Trial Overview The study tests VRDN-001, a monoclonal antibody targeting the IGF-1R receptor which could reduce inflammation in TED patients. It's being compared against a placebo in different phases of trials to assess safety, tolerability, and how it's processed by the body.

How Is the Trial Designed?

Group I: Phase 3 Cohort (THRIVE) veligrotug (VRDN-001) Experimental Treatment 1 Intervention

Participants with TED will be randomized to either veligrotug (VRDN-001) 10mg/kg or placebo.

Group II: Phase 3 Cohort (THRIVE) VRDN-001 Placebo Placebo Group 1 Intervention

Participants with TED will be randomized to either veligrotug (VRDN-001) 10mg/kg or placebo.

Who Is Running the Clinical Trial?

Viridian Therapeutics, Inc.

Lead Sponsor

Trials

7

Recruited

1,200+

Published Research Related to This Trial

Teprotumumab significantly reduces proptosis (eye bulging) and inflammation in patients with chronic Thyroid Eye Disease (TED), with an average reduction of 3.5 mm in proptosis after treatment.

In a study of 31 patients who received an average of 7 infusions, 67% of those with diplopia (double vision) experienced a significant improvement, and there was a notable reduction in both muscle and fat tissue volume in the orbits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teprotumumab for the treatment of chronic thyroid eye disease. Ugradar, S., Kang, J., Kossler, AL., et al.[2022]

In a study of 18 patients with thyroid eye disease who did not respond to multiple steroid treatments, Tocilizumab significantly improved disease activity, as shown by a mean reduction of 5.89 points in the Clinical Activity Score (CAS).

Tocilizumab also led to a substantial decrease in thyroid-stimulating immunoglobulin (TSI) levels by 76.18% and improved symptoms such as proptosis and extraocular motility, with no severe side effects reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of active corticosteroid-resistant graves' orbitopathy. Pérez-Moreiras, JV., Alvarez-López, A., Gómez, EC.[2022]

Teprotumumab, used for treating thyroid eye disease, effectively targets the insulin-like growth factor-1 receptor (IGF-1R), but it has been associated with common adverse effects such as hyperglycemia (10%-30% incidence) and hearing changes, which can range from mild ear pressure to hearing loss.

The review highlights the importance of considering these potential risks when using teprotumumab, suggesting that future therapies targeting IGF-1R should address these adverse effects to improve patient safety and treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Adverse Effects Profile of Teprotumumab. Stan, MN., Krieger, CC.[2023]

Teprotumumab, a monoclonal antibody targeting the IGF-1 receptor, has been shown to significantly improve symptoms of thyroid eye disease (TED) in two clinical trials involving 170 patients, with a responder rate of 69% compared to 20% for placebo in the phase 2 study.

The treatment resulted in a substantial reduction in proptosis (eye bulging) and clinical activity scores, with over half of the responders maintaining their improvement for up to 51 weeks after treatment, although it is associated with some common side effects like muscle spasms and nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teprotumumab: Interpreting the Clinical Trials in the Context of Thyroid Eye Disease Pathogenesis and Current Therapies. Winn, BJ., Kersten, RC.[2021]

Teprotumumab, an IGF-1R antagonist antibody, has shown efficacy and safety in treating moderate-to-severe thyroid eye disease (TED) in phase 2 and 3 clinical trials, leading to significant improvements in proptosis for patients.

This targeted therapy represents a shift in TED management, as it not only addresses symptoms but also modifies the disease course, potentially improving long-term patient outcomes compared to traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A New Era in the Treatment of Thyroid Eye Disease. Patel, A., Yang, H., Douglas, RS.[2020]

Teprotumumab is an effective treatment for thyroid eye disease (TED), showing significant efficacy in reducing inflammation and proptosis in both acute (<2 years) and chronic (>2 years) cases, primarily by decreasing orbital fat and muscle volume.

While teprotumumab is a powerful option for TED, it is associated with side effects such as muscle spasms, hearing loss, and hyperglycemia, and there are concerns about its potential link to inflammatory bowel disease flares.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Paradigm Shift in the Management of Thyroid Eye Disease How Teprotumumab Has Changed the Therapeutic Interface. Ugradar, S., Kossler, AL., Douglas, R., et al.[2022]

Teprotumumab (Tepro) effectively inhibits hyaluronan (HA) production in orbital fibroblasts from patients with thyroid eye disease (TED) by blocking the crosstalk between TSH receptors (TSHR) and IGF1 receptors (IGF1R), which is crucial for the disease's pathogenesis.

The study demonstrated that Tepro does not bind to TSHRs but still reduces HA production stimulated by TSHR/IGF1R crosstalk, indicating that its mechanism of action in treating TED involves disrupting this interaction rather than directly targeting TSHRs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of TSH/IGF-1 Receptor Crosstalk by Teprotumumab as a Treatment Modality of Thyroid Eye Disease. Krieger, CC., Sui, X., Kahaly, GJ., et al.[2022]

Teprotumumab, an IGF-1R inhibitor approved for thyroid eye disease, highlights the therapeutic potential of targeting IGF-1 and its receptor, but its systemic effects and local side effects in the eye need careful consideration.

Research shows that IGF-1 influences various ocular processes, including growth, inflammation, and retinal angiogenesis, but more studies are needed to fully understand the implications of anti-IGF-1R treatments on eye health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Insulin-like Growth Factor-1 and Its Receptor in the Eye: A Review and Implications for IGF-1R Inhibition. Truong, T., Silkiss, RZ.[2023]

Teprotumumab, a monoclonal antibody targeting the insulin-like growth factor-I receptor, has shown an 83% response rate in reducing proptosis (eye bulging) in patients with thyroid eye disease, indicating its efficacy in treating this condition.

The treatment is generally well tolerated, with common side effects including muscle spasms, nausea, and fatigue, suggesting that while it is effective, patients should be monitored for these adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teprotumumab for the treatment of thyroid eye disease. Ju, Y., Yang, J.[2021]

Teprotumumab (TEPEZZA®) is the first approved therapy for thyroid eye disease (TED) in the USA, showing significant improvements in symptoms like proptosis and overall quality of life in phase II and III trials with adults suffering from moderate-to-severe TED.

The treatment was generally well tolerated, with some adverse effects like muscle spasms and hearing loss, but it maintained clinical benefits for up to 51 weeks after treatment, marking a significant advancement in managing TED symptoms that were previously difficult to treat.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teprotumumab: A Review in Thyroid Eye Disease. Nie, T., Lamb, YN.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12545473/

OR31-04 Efficacy and Safety of Veligrotug (VRDN-001), a Full ... OR31-04 Efficacy and Safety of Veligrotug (VRDN-001), a Full Antagonist Monoclonal Antibody to IGF-1 Receptor, in Active Thyroid Eye Disease ( ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05176639

NCT05176639 | A Safety, Tolerability and Efficacy Study of ... A Safety, Tolerability and Efficacy Study of Veligrotug (VRDN 001) in Healthy Volunteers and Participants With Thyroid Eye Disease (TED) ( THRIVE ) (THRIVE).

3. investors.viridiantherapeutics.com investors.viridiantherapeutics.com/news/news-details/2025/Viridian-Therapeutics-Announces-Positive-Long-Term-Durability-Data-from-the-Veligrotug-Phase-3-THRIVE-Clinical-Trial-in-Patients-with-Active-Thyroid-Eye-Disease-TED/default.aspx

News Details 70% of patients treated with veligrotug in THRIVE who were proptosis responders at week 15 maintained their response at week 52 -.

4. viridiantherapeutics.com viridiantherapeutics.com/pipeline/ted-programs/

Thyroid Eye Disease Programs - Viridian Therapeutics, Inc. Viridian's lead product candidate, veligrotug (VRDN-001), is a potential best-in-class, IV monoclonal antibody targeting IGF-1R. veligrotug (VRDN-001) acts ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06021054

NCT06021054 | An Efficacy, Safety, and Tolerability Study ... This is a clinical trial assessing the efficacy, safety, and tolerability of an investigational drug, veligrotug (VRDN-001), in participants with chronic ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05176639

NCT05176639 | A Safety, Tolerability and Efficacy Study of ... A Safety, Tolerability and Efficacy Study of Veligrotug (VRDN 001) in Healthy Volunteers and Participants With Thyroid Eye Disease (TED) ( THRIVE ) (THRIVE).

7. viridiantherapeutics.com viridiantherapeutics.com/document/vrdn-001-a-potent-and-selective-insulin-like-growth-factor-1-receptor-igf-1r-antagonist-antibody-for-thyroid-eye-disease-ted-phase-1-safety-and-pharmacodynamic-results-in-healthy-volunteers/

VRDN-001, A Potent and Selective Insulin-Like Growth ... VRDN-001, A Potent and Selective Insulin-Like Growth Factor-1 Receptor (IGF-1R) Antagonist Antibody for Thyroid Eye Disease (TED): Interim Phase 1 Safety ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06384547

Study Details | NCT06384547 | A Randomized, Controlled, ... The primary objective of this clinical trial is to evaluate the safety and tolerability of VRDN-001 in patients with TED. Detailed Description. A randomized, ...